Paul Shitabata, MD

Perniosis, or chilblain, is characterized by localized, tender, erythematous skin lesions that occur as an abnormal reaction to exposure to cold and damp conditions. Although the lesions favor the distal extremities, perniosis may present anywhere on the body. Lesions can develop within hours to days following exposure to temperature less than 10°C or damp environments with greater than 60% humidity.¹ Acute cases may lead to pruritus and tenderness, whereas chronic cases may involve lesions that blister or ulcerate and can take weeks to heal. We report an unusual case of erythematous plaques arising on the buttocks of a 73-year-old woman using ice pack treatments for chronic low back pain.

Case Report

A 73-year-old woman presented with recurrent tender lesions on the buttocks of 5 years’ duration. Her medical history was remarkable for hypertension, hypothyroidism, and lumbar spinal fusion surgery 5 years prior. Physical examination revealed indurated erythematous plaques with areas of erosions on the left buttock with some involvement of the right buttock (Figure 1).

ct10205e24_fig1.png

After a trial of oral valacyclovir for presumed herpes simplex infection provided no relief, a punch biopsy of the left buttock was performed, which revealed a cell-poor interface dermatitis with superficial and deep perivascular and periadnexal lymphocytic infiltrates (Figure 2). Perieccrine lymphocytes were present in a small portion of the reticular dermis (Figure 3). The patient revealed she had been sitting on ice packs for several hours daily since the lumbar spinal fusion surgery 5 years prior to alleviate chronic low back pain.

ct10205e24_fig2.png

ct10205e24_fig3.png

Based on the clinicopathologic correlation, a diagnosis of perniosis secondary to ice pack therapy was made. An evaluation for concomitant or underlying connective tissue disease (CTD) including a complete blood cell count with sedimentation rate, antinuclear antibodies (ANAs), serum protein electrophoresis, and serum levels of cryoglobulins and complement components was unremarkable. Our patient was treated with simple analgesia and was encouraged to avoid direct contact with ice packs for extended periods of time. Because of her low back pain, she continued to use ice packs but readjusted them sporadically and decreased frequency of use. She had complete resolution of the lesions at 6-month follow-up.

Comment

Perniosis is a self-limited condition, manifesting as erythematous plaques or nodules following exposure to cold and damp conditions. It was first reported in 1902 by Hochsinger² as tender submental plaques occurring in children after exposure to cold weather. Since then, reports of perniosis have been described in equestrians and long-distance cyclists as well as in the context of other outdoor activities.^3-5 In all cases, patients developed perniosis at sites of exposure to cold or damp conditions.

Perniosis arising in patients using ice pack therapy is a rare and recent phenomenon, with only 3 other known reported cases.^6,7 In all cases, including ours, patients reported treating chronic low back pain with ice packs for more than 2 hours per day. Clinical presentations included erythematous to purpuric plaques with ulceration on the lower back or buttocks that reoccurred with subsequent use of ice packs. No concomitant CTD was reported.⁶

Much controversy exists as to whether idiopathic perniosis (IP) increases susceptibility to acquiring an autoimmune disease or if IP is a form of CTD that follows a more indolent course.⁸ In a prospective study of 33 patients with underlying IP, no patients developed lupus erythematosus (LE), with a median follow-up of 38 months.⁹ A study by Crowson and Magro⁸ revealed that 18 of 39 patients with perniotic lesions had an associated systemic disease including LE, human immunodeficiency virus, viral hepatitis, rheumatoid arthritis, cryofibrinogenemia, hypergammaglobulinemia, iritis, or Crohn disease. Of the 21 other patients who had no underlying CTD or systemic disease, 10 had a positive ANA test but no systemic symptoms; therefore, all 21 of these patients were classified as cases of IP.⁸

Cutaneous biopsy to distinguish between IP and autoimmune perniosis remains controversial; perniotic lesions and discoid LE share histopathologic features,⁹ as was evident with our case, which demonstrated overlapping findings of vacuolar change with superficial and deep perivascular and periadnexal lymphoid infiltrates. Typical features of IP include thrombosed capillaries in the papillary dermis and lymphocytic exocytosis localized to the acrosyringia, whereas secondary perniosis has superficial and deep perivascular and perieccrine lymphocytic infiltrates with vascular thrombosis in the reticular dermis. Vascular ectasia, dermal mucinosis, basement membrane zone thickening, and erythrocyte extravasation are not reliable and may be seen in both cases.⁸ One study revealed the only significant difference between both entities was the perieccrine distribution of lymphocytic infiltrate in cases of IP (P=.007), whereas an absence of perieccrine involvement was noted in autoimmune cases.⁹

Direct immunofluorescence (DIF) may help differentiate IP from autoimmune perniosis. In a prospective study by Viguier et al,⁹ 6 of 9 patients with IP had negative DIF and 3 had slight nonspecific C3 immunoreactivity of dermal vessels. Conversely, in patients with autoimmune perniosis, positive DIF with the lupus band test was seen in 3 of 7 patients, all who had a positive ANA test⁹; however, positive ANA levels also were reported in patients with autoimmune perniosis but negative DIF, suggesting that DIF lacks specificity in diagnosing autoimmune perniosis.

Although histopathologic findings bear similarities to LE, there are no guidelines to suggest for or against laboratory testing for CTD in patients presenting with perniosis. Some investigators have suggested that any patient with clinical features suggestive of perniosis should undergo laboratory evaluation including a complete blood cell count and assessment for antibodies to Ro, ANA, rheumatoid factor, cryofibrinogens, and antiphospholipid antibodies.⁹ Serum protein electrophoresis and immunofixation electrophoresis may be done to exclude monoclonal gammopathy.

For idiopathic cases, treatment is aimed at limiting or removing cold exposure. Patients should be advised regarding the use of long-term ice pack use and the potential development of perniosis. For chronic perniosis lasting beyond several weeks, a combination of a slow taper of oral prednisone, hydroxychloroquine, and quinacrine has been successful in patients with persistent lesions despite making environmental modifications.³ Intralesional triamcinolone acetonide and nifedipine also have been effective in perniotic hand lesions.¹⁰

Conclusion

We report a rare case of perniosis on the buttocks that arose in a patient who utilized ice packs for treatment of chronic low back pain. Ice pack–induced perniosis may be an underreported entity. Histopathologic examination is nondescript, as overlapping features of perniosis and LE have been observed with no underlying CTD present. Correlation with patient history and clinical examination is paramount in diagnosis and management.

Perniosis, or chilblain, is characterized by localized, tender, erythematous skin lesions that occur as an abnormal reaction to exposure to cold and damp conditions. Although the lesions favor the distal extremities, perniosis may present anywhere on the body. Lesions can develop within hours to days following exposure to temperature less than 10°C or damp environments with greater than 60% humidity.¹ Acute cases may lead to pruritus and tenderness, whereas chronic cases may involve lesions that blister or ulcerate and can take weeks to heal. We report an unusual case of erythematous plaques arising on the buttocks of a 73-year-old woman using ice pack treatments for chronic low back pain.

Case Report

A 73-year-old woman presented with recurrent tender lesions on the buttocks of 5 years’ duration. Her medical history was remarkable for hypertension, hypothyroidism, and lumbar spinal fusion surgery 5 years prior. Physical examination revealed indurated erythematous plaques with areas of erosions on the left buttock with some involvement of the right buttock (Figure 1).

ct10205e24_fig1.png

After a trial of oral valacyclovir for presumed herpes simplex infection provided no relief, a punch biopsy of the left buttock was performed, which revealed a cell-poor interface dermatitis with superficial and deep perivascular and periadnexal lymphocytic infiltrates (Figure 2). Perieccrine lymphocytes were present in a small portion of the reticular dermis (Figure 3). The patient revealed she had been sitting on ice packs for several hours daily since the lumbar spinal fusion surgery 5 years prior to alleviate chronic low back pain.

ct10205e24_fig2.png

ct10205e24_fig3.png

Based on the clinicopathologic correlation, a diagnosis of perniosis secondary to ice pack therapy was made. An evaluation for concomitant or underlying connective tissue disease (CTD) including a complete blood cell count with sedimentation rate, antinuclear antibodies (ANAs), serum protein electrophoresis, and serum levels of cryoglobulins and complement components was unremarkable. Our patient was treated with simple analgesia and was encouraged to avoid direct contact with ice packs for extended periods of time. Because of her low back pain, she continued to use ice packs but readjusted them sporadically and decreased frequency of use. She had complete resolution of the lesions at 6-month follow-up.

Comment

Perniosis is a self-limited condition, manifesting as erythematous plaques or nodules following exposure to cold and damp conditions. It was first reported in 1902 by Hochsinger² as tender submental plaques occurring in children after exposure to cold weather. Since then, reports of perniosis have been described in equestrians and long-distance cyclists as well as in the context of other outdoor activities.^3-5 In all cases, patients developed perniosis at sites of exposure to cold or damp conditions.

Perniosis arising in patients using ice pack therapy is a rare and recent phenomenon, with only 3 other known reported cases.^6,7 In all cases, including ours, patients reported treating chronic low back pain with ice packs for more than 2 hours per day. Clinical presentations included erythematous to purpuric plaques with ulceration on the lower back or buttocks that reoccurred with subsequent use of ice packs. No concomitant CTD was reported.⁶

Much controversy exists as to whether idiopathic perniosis (IP) increases susceptibility to acquiring an autoimmune disease or if IP is a form of CTD that follows a more indolent course.⁸ In a prospective study of 33 patients with underlying IP, no patients developed lupus erythematosus (LE), with a median follow-up of 38 months.⁹ A study by Crowson and Magro⁸ revealed that 18 of 39 patients with perniotic lesions had an associated systemic disease including LE, human immunodeficiency virus, viral hepatitis, rheumatoid arthritis, cryofibrinogenemia, hypergammaglobulinemia, iritis, or Crohn disease. Of the 21 other patients who had no underlying CTD or systemic disease, 10 had a positive ANA test but no systemic symptoms; therefore, all 21 of these patients were classified as cases of IP.⁸

Cutaneous biopsy to distinguish between IP and autoimmune perniosis remains controversial; perniotic lesions and discoid LE share histopathologic features,⁹ as was evident with our case, which demonstrated overlapping findings of vacuolar change with superficial and deep perivascular and periadnexal lymphoid infiltrates. Typical features of IP include thrombosed capillaries in the papillary dermis and lymphocytic exocytosis localized to the acrosyringia, whereas secondary perniosis has superficial and deep perivascular and perieccrine lymphocytic infiltrates with vascular thrombosis in the reticular dermis. Vascular ectasia, dermal mucinosis, basement membrane zone thickening, and erythrocyte extravasation are not reliable and may be seen in both cases.⁸ One study revealed the only significant difference between both entities was the perieccrine distribution of lymphocytic infiltrate in cases of IP (P=.007), whereas an absence of perieccrine involvement was noted in autoimmune cases.⁹

Direct immunofluorescence (DIF) may help differentiate IP from autoimmune perniosis. In a prospective study by Viguier et al,⁹ 6 of 9 patients with IP had negative DIF and 3 had slight nonspecific C3 immunoreactivity of dermal vessels. Conversely, in patients with autoimmune perniosis, positive DIF with the lupus band test was seen in 3 of 7 patients, all who had a positive ANA test⁹; however, positive ANA levels also were reported in patients with autoimmune perniosis but negative DIF, suggesting that DIF lacks specificity in diagnosing autoimmune perniosis.

Although histopathologic findings bear similarities to LE, there are no guidelines to suggest for or against laboratory testing for CTD in patients presenting with perniosis. Some investigators have suggested that any patient with clinical features suggestive of perniosis should undergo laboratory evaluation including a complete blood cell count and assessment for antibodies to Ro, ANA, rheumatoid factor, cryofibrinogens, and antiphospholipid antibodies.⁹ Serum protein electrophoresis and immunofixation electrophoresis may be done to exclude monoclonal gammopathy.

For idiopathic cases, treatment is aimed at limiting or removing cold exposure. Patients should be advised regarding the use of long-term ice pack use and the potential development of perniosis. For chronic perniosis lasting beyond several weeks, a combination of a slow taper of oral prednisone, hydroxychloroquine, and quinacrine has been successful in patients with persistent lesions despite making environmental modifications.³ Intralesional triamcinolone acetonide and nifedipine also have been effective in perniotic hand lesions.¹⁰

Conclusion

We report a rare case of perniosis on the buttocks that arose in a patient who utilized ice packs for treatment of chronic low back pain. Ice pack–induced perniosis may be an underreported entity. Histopathologic examination is nondescript, as overlapping features of perniosis and LE have been observed with no underlying CTD present. Correlation with patient history and clinical examination is paramount in diagnosis and management.

Perniosis, or chilblain, is characterized by localized, tender, erythematous skin lesions that occur as an abnormal reaction to exposure to cold and damp conditions. Although the lesions favor the distal extremities, perniosis may present anywhere on the body. Lesions can develop within hours to days following exposure to temperature less than 10°C or damp environments with greater than 60% humidity.¹ Acute cases may lead to pruritus and tenderness, whereas chronic cases may involve lesions that blister or ulcerate and can take weeks to heal. We report an unusual case of erythematous plaques arising on the buttocks of a 73-year-old woman using ice pack treatments for chronic low back pain.

Case Report

A 73-year-old woman presented with recurrent tender lesions on the buttocks of 5 years’ duration. Her medical history was remarkable for hypertension, hypothyroidism, and lumbar spinal fusion surgery 5 years prior. Physical examination revealed indurated erythematous plaques with areas of erosions on the left buttock with some involvement of the right buttock (Figure 1).

ct10205e24_fig1.png

After a trial of oral valacyclovir for presumed herpes simplex infection provided no relief, a punch biopsy of the left buttock was performed, which revealed a cell-poor interface dermatitis with superficial and deep perivascular and periadnexal lymphocytic infiltrates (Figure 2). Perieccrine lymphocytes were present in a small portion of the reticular dermis (Figure 3). The patient revealed she had been sitting on ice packs for several hours daily since the lumbar spinal fusion surgery 5 years prior to alleviate chronic low back pain.

ct10205e24_fig2.png

ct10205e24_fig3.png

Based on the clinicopathologic correlation, a diagnosis of perniosis secondary to ice pack therapy was made. An evaluation for concomitant or underlying connective tissue disease (CTD) including a complete blood cell count with sedimentation rate, antinuclear antibodies (ANAs), serum protein electrophoresis, and serum levels of cryoglobulins and complement components was unremarkable. Our patient was treated with simple analgesia and was encouraged to avoid direct contact with ice packs for extended periods of time. Because of her low back pain, she continued to use ice packs but readjusted them sporadically and decreased frequency of use. She had complete resolution of the lesions at 6-month follow-up.

Comment

Perniosis is a self-limited condition, manifesting as erythematous plaques or nodules following exposure to cold and damp conditions. It was first reported in 1902 by Hochsinger² as tender submental plaques occurring in children after exposure to cold weather. Since then, reports of perniosis have been described in equestrians and long-distance cyclists as well as in the context of other outdoor activities.^3-5 In all cases, patients developed perniosis at sites of exposure to cold or damp conditions.

Perniosis arising in patients using ice pack therapy is a rare and recent phenomenon, with only 3 other known reported cases.^6,7 In all cases, including ours, patients reported treating chronic low back pain with ice packs for more than 2 hours per day. Clinical presentations included erythematous to purpuric plaques with ulceration on the lower back or buttocks that reoccurred with subsequent use of ice packs. No concomitant CTD was reported.⁶

Much controversy exists as to whether idiopathic perniosis (IP) increases susceptibility to acquiring an autoimmune disease or if IP is a form of CTD that follows a more indolent course.⁸ In a prospective study of 33 patients with underlying IP, no patients developed lupus erythematosus (LE), with a median follow-up of 38 months.⁹ A study by Crowson and Magro⁸ revealed that 18 of 39 patients with perniotic lesions had an associated systemic disease including LE, human immunodeficiency virus, viral hepatitis, rheumatoid arthritis, cryofibrinogenemia, hypergammaglobulinemia, iritis, or Crohn disease. Of the 21 other patients who had no underlying CTD or systemic disease, 10 had a positive ANA test but no systemic symptoms; therefore, all 21 of these patients were classified as cases of IP.⁸

Cutaneous biopsy to distinguish between IP and autoimmune perniosis remains controversial; perniotic lesions and discoid LE share histopathologic features,⁹ as was evident with our case, which demonstrated overlapping findings of vacuolar change with superficial and deep perivascular and periadnexal lymphoid infiltrates. Typical features of IP include thrombosed capillaries in the papillary dermis and lymphocytic exocytosis localized to the acrosyringia, whereas secondary perniosis has superficial and deep perivascular and perieccrine lymphocytic infiltrates with vascular thrombosis in the reticular dermis. Vascular ectasia, dermal mucinosis, basement membrane zone thickening, and erythrocyte extravasation are not reliable and may be seen in both cases.⁸ One study revealed the only significant difference between both entities was the perieccrine distribution of lymphocytic infiltrate in cases of IP (P=.007), whereas an absence of perieccrine involvement was noted in autoimmune cases.⁹

Direct immunofluorescence (DIF) may help differentiate IP from autoimmune perniosis. In a prospective study by Viguier et al,⁹ 6 of 9 patients with IP had negative DIF and 3 had slight nonspecific C3 immunoreactivity of dermal vessels. Conversely, in patients with autoimmune perniosis, positive DIF with the lupus band test was seen in 3 of 7 patients, all who had a positive ANA test⁹; however, positive ANA levels also were reported in patients with autoimmune perniosis but negative DIF, suggesting that DIF lacks specificity in diagnosing autoimmune perniosis.

Although histopathologic findings bear similarities to LE, there are no guidelines to suggest for or against laboratory testing for CTD in patients presenting with perniosis. Some investigators have suggested that any patient with clinical features suggestive of perniosis should undergo laboratory evaluation including a complete blood cell count and assessment for antibodies to Ro, ANA, rheumatoid factor, cryofibrinogens, and antiphospholipid antibodies.⁹ Serum protein electrophoresis and immunofixation electrophoresis may be done to exclude monoclonal gammopathy.

For idiopathic cases, treatment is aimed at limiting or removing cold exposure. Patients should be advised regarding the use of long-term ice pack use and the potential development of perniosis. For chronic perniosis lasting beyond several weeks, a combination of a slow taper of oral prednisone, hydroxychloroquine, and quinacrine has been successful in patients with persistent lesions despite making environmental modifications.³ Intralesional triamcinolone acetonide and nifedipine also have been effective in perniotic hand lesions.¹⁰

Conclusion

We report a rare case of perniosis on the buttocks that arose in a patient who utilized ice packs for treatment of chronic low back pain. Ice pack–induced perniosis may be an underreported entity. Histopathologic examination is nondescript, as overlapping features of perniosis and LE have been observed with no underlying CTD present. Correlation with patient history and clinical examination is paramount in diagnosis and management.

Fibrofolliculomas and trichodiscomas typically present on the head or neck as smooth, flesh-colored, dome-shaped papules. These two entities are considered to constitute two separate time points on a spectrum of histopathologic changes in mantleoma differentiation.¹ Histologically, both are benign hamartomas of the pilosebaceous subunit and collectively are known as mantleomas. We present an unusual case of a concomitant fibrofolliculoma and trichodiscoma on the abdomen.

Case Report

An asymptomatic 54-year-old man presented for a routine full-body skin examination. A solitary, 2×1-cm, subcutaneous, doughy, mobile nodule was found on the left side of the abdomen with an overlying 2-mm yellow fleshy papule. The patient declined excision of the lesion, and it was recommended that he return for follow-up 3 months later.

The patient did not present for follow-up until 4.5 years later, at which point the lesion had grown to 3.0×2.5 cm in size. An excision was performed, at which time the lesion was noted to be cystic, extruding an oily, yellow-white liquid. Bacterial culture was negative. Histopathologic sections showed a dome-shaped papule with connection to the overlying epidermis. Epithelial extensions from the infundibular epithelium formed a fenestrated pattern surrounding a fibrous and mucinous stroma (Figure, A and B). The differential diagnosis at this time included an epidermal inclusion cyst, fibroma, intradermal nevus, verruca, hemangioma, angiofibroma, and lipoma.^2-4

The same lesion cut in a different plane of sectioning showed an expansile dermal nodule comprising clusters of sebaceous lobules surrounding a fibrous and mucinous stroma. Within the second lesion, fibrous and stromal components predominated over epithelial components (Figure, C). A diagnosis of fibrofolliculoma showing features of a trichodiscoma arising in the unusual location of the abdomen was made.

ct098010030_e_fig.png

Comment

Solitary fibrofolliculomas and trichodiscomas are flesh-colored, dome-shaped papules that generally present on the face, specifically on the chin, nose, cheeks, ears, and eyebrows without considerable symptoms.^2,4,5 Clinically, fibrofolliculomas are indistinguishable from trichodiscomas but demonstrate different features on biopsy.^1,5

Fibrofolliculomas and trichodiscomas are well known for their association with Birt-Hogg-Dubé (BHD) syndrome when they present concomitantly and typically arise earlier in the third decade of life than solitary fibrofolliculomas; however, there have been reports of solitary fibrofolliculomas in patients aged 1 to 36 years.^4,6 The triad of BHD syndrome consists of multiple fibrofolliculomas, trichodiscomas, and acrochordons, and it is acquired in an autosomal-dominant manner, unlike solitary fibrofolliculomas, which typically are not inherited. Birt-Hogg-Dubé syndrome is caused by a mutation in the FLCN gene that codes for the tumor-suppressor protein folliculin, which when mutated can cause unregulated proliferation of cells.⁷ Solitary fibrofolliculomas and the multiple fibrofolliculomas seen in BHD syndrome are histologically similar.

Fibrofolliculoma can be clinically indistinguishable from fibroepithelioma of Pinkus, perifollicular fibroma, trichilemmoma, trichodiscoma, trichoepithelioma, and trichofolliculoma. All typically present clinically as flesh-colored papules,¹ although histologic distinction can be made (Table).^5,8-13

Fibrofolliculoma is a benign hamartoma that arises from the pilosebaceous follicle and consists of an expansion of the fibrous root sheath, which typically surrounds the hair follicle along with proliferating bands or ribbons of perifollicular connective tissue. As such, the hair follicle may be dilated and filled with keratin in the expanded infundibulum.⁸ Follicles also may be surrounded by a myxoid stroma.² In contrast, trichodiscoma is characterized by connective tissue with mature sebaceous lobules in the periphery. It has a myxoid stroma, as opposed to the more fibrous stroma seen in fibrofolliculomas.

CT098010030_e_Table.JPG

Ackerman et al¹ considered both fibrofolliculomas and trichodiscomas to be hamartomas of the epithelial hair follicle. The exact etiology of each of these hamartomas is unknown, but the undifferentiated epithelial strands protruding from the hair follicle in a fibrofolliculoma lie in close proximity to sebaceous glands. Furthermore, the authors postulated that fibrofolliculomas and trichodiscomas constitute a spectrum that encompasses the differentiation process of a mantleoma, with fibrofolliculoma representing the beginning of mantleoma differentiation and trichodiscoma representing the end. This end stage of follicular differentiation is one in which there is a predominant stroma and the previously undifferentiated epithelium has formed into sebaceous ducts and lobules in the stroma.¹

Most cases of fibrofolliculoma and/or trichodiscoma arise in areas of dense sebaceous follicle concentration (eg, face), further supporting the hypothesis that sebaceous gland proliferation contributes to fibrofolliculoma.¹⁴ The case described here, with the fibrofolliculoma arising on the abdomen in conjunction with a trichodiscoma, is therefore worth noting because its location differs from what has been observed in previously reported cases.⁴

There are both surgical and medical options for treatment of fibrofolliculoma. Although surgical excision is an option for a single lesion, patients with multiple fibrofolliculomas or BHD may prefer removal with the combined CO₂ laser and erbium-doped YAG laser.¹⁵

Conclusion

We present a rare case of concomitant fibrofolliculoma and trichodiscoma arising on the unusual location of the abdomen. This report highlights the histopathologic features of multiple adnexal tumors and emphasizes the importance of biopsy for differentiating fibrofolliculoma and trichodiscoma.

Fibrofolliculomas and trichodiscomas typically present on the head or neck as smooth, flesh-colored, dome-shaped papules. These two entities are considered to constitute two separate time points on a spectrum of histopathologic changes in mantleoma differentiation.¹ Histologically, both are benign hamartomas of the pilosebaceous subunit and collectively are known as mantleomas. We present an unusual case of a concomitant fibrofolliculoma and trichodiscoma on the abdomen.

Case Report

An asymptomatic 54-year-old man presented for a routine full-body skin examination. A solitary, 2×1-cm, subcutaneous, doughy, mobile nodule was found on the left side of the abdomen with an overlying 2-mm yellow fleshy papule. The patient declined excision of the lesion, and it was recommended that he return for follow-up 3 months later.

The patient did not present for follow-up until 4.5 years later, at which point the lesion had grown to 3.0×2.5 cm in size. An excision was performed, at which time the lesion was noted to be cystic, extruding an oily, yellow-white liquid. Bacterial culture was negative. Histopathologic sections showed a dome-shaped papule with connection to the overlying epidermis. Epithelial extensions from the infundibular epithelium formed a fenestrated pattern surrounding a fibrous and mucinous stroma (Figure, A and B). The differential diagnosis at this time included an epidermal inclusion cyst, fibroma, intradermal nevus, verruca, hemangioma, angiofibroma, and lipoma.^2-4

The same lesion cut in a different plane of sectioning showed an expansile dermal nodule comprising clusters of sebaceous lobules surrounding a fibrous and mucinous stroma. Within the second lesion, fibrous and stromal components predominated over epithelial components (Figure, C). A diagnosis of fibrofolliculoma showing features of a trichodiscoma arising in the unusual location of the abdomen was made.

ct098010030_e_fig.png

Comment

Solitary fibrofolliculomas and trichodiscomas are flesh-colored, dome-shaped papules that generally present on the face, specifically on the chin, nose, cheeks, ears, and eyebrows without considerable symptoms.^2,4,5 Clinically, fibrofolliculomas are indistinguishable from trichodiscomas but demonstrate different features on biopsy.^1,5

Fibrofolliculomas and trichodiscomas are well known for their association with Birt-Hogg-Dubé (BHD) syndrome when they present concomitantly and typically arise earlier in the third decade of life than solitary fibrofolliculomas; however, there have been reports of solitary fibrofolliculomas in patients aged 1 to 36 years.^4,6 The triad of BHD syndrome consists of multiple fibrofolliculomas, trichodiscomas, and acrochordons, and it is acquired in an autosomal-dominant manner, unlike solitary fibrofolliculomas, which typically are not inherited. Birt-Hogg-Dubé syndrome is caused by a mutation in the FLCN gene that codes for the tumor-suppressor protein folliculin, which when mutated can cause unregulated proliferation of cells.⁷ Solitary fibrofolliculomas and the multiple fibrofolliculomas seen in BHD syndrome are histologically similar.

Fibrofolliculoma can be clinically indistinguishable from fibroepithelioma of Pinkus, perifollicular fibroma, trichilemmoma, trichodiscoma, trichoepithelioma, and trichofolliculoma. All typically present clinically as flesh-colored papules,¹ although histologic distinction can be made (Table).^5,8-13

Fibrofolliculoma is a benign hamartoma that arises from the pilosebaceous follicle and consists of an expansion of the fibrous root sheath, which typically surrounds the hair follicle along with proliferating bands or ribbons of perifollicular connective tissue. As such, the hair follicle may be dilated and filled with keratin in the expanded infundibulum.⁸ Follicles also may be surrounded by a myxoid stroma.² In contrast, trichodiscoma is characterized by connective tissue with mature sebaceous lobules in the periphery. It has a myxoid stroma, as opposed to the more fibrous stroma seen in fibrofolliculomas.

CT098010030_e_Table.JPG

Ackerman et al¹ considered both fibrofolliculomas and trichodiscomas to be hamartomas of the epithelial hair follicle. The exact etiology of each of these hamartomas is unknown, but the undifferentiated epithelial strands protruding from the hair follicle in a fibrofolliculoma lie in close proximity to sebaceous glands. Furthermore, the authors postulated that fibrofolliculomas and trichodiscomas constitute a spectrum that encompasses the differentiation process of a mantleoma, with fibrofolliculoma representing the beginning of mantleoma differentiation and trichodiscoma representing the end. This end stage of follicular differentiation is one in which there is a predominant stroma and the previously undifferentiated epithelium has formed into sebaceous ducts and lobules in the stroma.¹

Most cases of fibrofolliculoma and/or trichodiscoma arise in areas of dense sebaceous follicle concentration (eg, face), further supporting the hypothesis that sebaceous gland proliferation contributes to fibrofolliculoma.¹⁴ The case described here, with the fibrofolliculoma arising on the abdomen in conjunction with a trichodiscoma, is therefore worth noting because its location differs from what has been observed in previously reported cases.⁴

There are both surgical and medical options for treatment of fibrofolliculoma. Although surgical excision is an option for a single lesion, patients with multiple fibrofolliculomas or BHD may prefer removal with the combined CO₂ laser and erbium-doped YAG laser.¹⁵

Conclusion

We present a rare case of concomitant fibrofolliculoma and trichodiscoma arising on the unusual location of the abdomen. This report highlights the histopathologic features of multiple adnexal tumors and emphasizes the importance of biopsy for differentiating fibrofolliculoma and trichodiscoma.

Fibrofolliculomas and trichodiscomas typically present on the head or neck as smooth, flesh-colored, dome-shaped papules. These two entities are considered to constitute two separate time points on a spectrum of histopathologic changes in mantleoma differentiation.¹ Histologically, both are benign hamartomas of the pilosebaceous subunit and collectively are known as mantleomas. We present an unusual case of a concomitant fibrofolliculoma and trichodiscoma on the abdomen.

Case Report

An asymptomatic 54-year-old man presented for a routine full-body skin examination. A solitary, 2×1-cm, subcutaneous, doughy, mobile nodule was found on the left side of the abdomen with an overlying 2-mm yellow fleshy papule. The patient declined excision of the lesion, and it was recommended that he return for follow-up 3 months later.

The patient did not present for follow-up until 4.5 years later, at which point the lesion had grown to 3.0×2.5 cm in size. An excision was performed, at which time the lesion was noted to be cystic, extruding an oily, yellow-white liquid. Bacterial culture was negative. Histopathologic sections showed a dome-shaped papule with connection to the overlying epidermis. Epithelial extensions from the infundibular epithelium formed a fenestrated pattern surrounding a fibrous and mucinous stroma (Figure, A and B). The differential diagnosis at this time included an epidermal inclusion cyst, fibroma, intradermal nevus, verruca, hemangioma, angiofibroma, and lipoma.^2-4

The same lesion cut in a different plane of sectioning showed an expansile dermal nodule comprising clusters of sebaceous lobules surrounding a fibrous and mucinous stroma. Within the second lesion, fibrous and stromal components predominated over epithelial components (Figure, C). A diagnosis of fibrofolliculoma showing features of a trichodiscoma arising in the unusual location of the abdomen was made.

ct098010030_e_fig.png

Comment

Solitary fibrofolliculomas and trichodiscomas are flesh-colored, dome-shaped papules that generally present on the face, specifically on the chin, nose, cheeks, ears, and eyebrows without considerable symptoms.^2,4,5 Clinically, fibrofolliculomas are indistinguishable from trichodiscomas but demonstrate different features on biopsy.^1,5

Fibrofolliculomas and trichodiscomas are well known for their association with Birt-Hogg-Dubé (BHD) syndrome when they present concomitantly and typically arise earlier in the third decade of life than solitary fibrofolliculomas; however, there have been reports of solitary fibrofolliculomas in patients aged 1 to 36 years.^4,6 The triad of BHD syndrome consists of multiple fibrofolliculomas, trichodiscomas, and acrochordons, and it is acquired in an autosomal-dominant manner, unlike solitary fibrofolliculomas, which typically are not inherited. Birt-Hogg-Dubé syndrome is caused by a mutation in the FLCN gene that codes for the tumor-suppressor protein folliculin, which when mutated can cause unregulated proliferation of cells.⁷ Solitary fibrofolliculomas and the multiple fibrofolliculomas seen in BHD syndrome are histologically similar.

Fibrofolliculoma can be clinically indistinguishable from fibroepithelioma of Pinkus, perifollicular fibroma, trichilemmoma, trichodiscoma, trichoepithelioma, and trichofolliculoma. All typically present clinically as flesh-colored papules,¹ although histologic distinction can be made (Table).^5,8-13

Fibrofolliculoma is a benign hamartoma that arises from the pilosebaceous follicle and consists of an expansion of the fibrous root sheath, which typically surrounds the hair follicle along with proliferating bands or ribbons of perifollicular connective tissue. As such, the hair follicle may be dilated and filled with keratin in the expanded infundibulum.⁸ Follicles also may be surrounded by a myxoid stroma.² In contrast, trichodiscoma is characterized by connective tissue with mature sebaceous lobules in the periphery. It has a myxoid stroma, as opposed to the more fibrous stroma seen in fibrofolliculomas.

CT098010030_e_Table.JPG

Ackerman et al¹ considered both fibrofolliculomas and trichodiscomas to be hamartomas of the epithelial hair follicle. The exact etiology of each of these hamartomas is unknown, but the undifferentiated epithelial strands protruding from the hair follicle in a fibrofolliculoma lie in close proximity to sebaceous glands. Furthermore, the authors postulated that fibrofolliculomas and trichodiscomas constitute a spectrum that encompasses the differentiation process of a mantleoma, with fibrofolliculoma representing the beginning of mantleoma differentiation and trichodiscoma representing the end. This end stage of follicular differentiation is one in which there is a predominant stroma and the previously undifferentiated epithelium has formed into sebaceous ducts and lobules in the stroma.¹

Most cases of fibrofolliculoma and/or trichodiscoma arise in areas of dense sebaceous follicle concentration (eg, face), further supporting the hypothesis that sebaceous gland proliferation contributes to fibrofolliculoma.¹⁴ The case described here, with the fibrofolliculoma arising on the abdomen in conjunction with a trichodiscoma, is therefore worth noting because its location differs from what has been observed in previously reported cases.⁴

There are both surgical and medical options for treatment of fibrofolliculoma. Although surgical excision is an option for a single lesion, patients with multiple fibrofolliculomas or BHD may prefer removal with the combined CO₂ laser and erbium-doped YAG laser.¹⁵

Conclusion

We present a rare case of concomitant fibrofolliculoma and trichodiscoma arising on the unusual location of the abdomen. This report highlights the histopathologic features of multiple adnexal tumors and emphasizes the importance of biopsy for differentiating fibrofolliculoma and trichodiscoma.

CASE REPORT

A 74-year-old woman presented with a painful lesion on the left lower leg that was getting larger and more edematous and erythematous over the last 5 months. She experienced numbness and burning of the left lower leg 1 year prior to the development of the lesion. A review of her medical history revealed an otherwise healthy woman with no constitutional symptoms of fever, chills, nausea, vomiting, diarrhea, or chest pain. The patient did not exhibit mucosal, genital, or nail involvement. Physical examination revealed a group of four 1-cm, ill-defined, irregularly bordered, violaceous plaques on the left anterior tibial leg with faint surrounding erythematous to violaceous patches (Figure 1). The plaques were tender to palpation with no bleeding or drainage.

ct102002031_e_fig1.png

An 8.0-mm punch biopsy of the lesion was obtained. Hematoxylin and eosin staining on low-power magnification demonstrated a diffuse lymphocytic inflammatory infiltrate in the dermis and subcutis. Notable sparing of the subepidermal area (free grenz zone) was present (Figure 2A). On higher power, centroblasts and immunoblasts were visualized alongside extravasated red blood cells (Figure 2B). A diagnosis of primary cutaneous diffuse large B-cell lymphoma, leg type (DLBCLLT) was made. Various immunohistochemical stains confirmed the diagnosis, including B-cell lymphoma 2 (BCL-2)(Figure 3A) and multiple myeloma oncogene 1 (MUM-1)(Figure 3B), which were highly positive in our patient. The patient had a negative bone marrow biopsy and positron emission tomography scan. She was started on rituximab infusions and multiple radiation treatments. At 2-year follow-up the lymphoma continued to recur despite radiation therapy.

ct102002031_e_fig2.png

ct102002031_e_fig3.png

COMMENT

Incidence and Clinical Characteristics

Primary cutaneous DLBCLLT is an intermediately aggressive form of primary cutaneous B-cell lymphoma (CBCL) that accounts for approximately 10% to 20% of all primary CBCLs and 1% to 3% of all cutaneous lymphomas.¹ Diffuse large B-cell lymphoma, leg type primarily affects elderly patients (median age, 70 years). Women are more commonly affected. Clinically, primary cutaneous DLBCLLT presents as red-brown to bluish nodules or tumors on one or both distal legs. Although referred to as leg-type diffuse large B-cell lymphoma, 10% to 15% of patients have lesions in anatomic areas other than the legs, most commonly the trunk.

Histopathology

The diagnosis of DLBCLLT is best made histologically. There is a dense inflammatory infiltrate present in the dermis and subcutis that may extend upward into the dermoepidermal junction. Often a subepidermal free grenz zone may be seen, and adnexal structures may be destroyed. This infiltrate is composed of confluent sheets of large round cells including centroblasts and immunoblasts.² Centroblasts are large cells that have nuclei with several small nucleoli adhering to the membrane, while immunoblasts are large round cells containing nuclei with large central nucleoli. Both centroblasts and immunoblasts stain positively for BCL-2. Centrocytes typically are absent. Staining for BCL-2 can be important in distinguishing DLBCLLT from other forms of CBCL. Diffuse large B-cell lymphoma, leg type also can demonstrate clusters of large atypical cells in the epidermis simulating epidermotropism and Pautrier microabscesses. Neoplastic cells in this condition may express monoclonal surface and cytoplasmic immunoglobulins. Primary cutaneous DLBCLLT typically is positive for B-cell markers CD20 and CD79a. Additionally, MUM-1/IRF4 (interferon regulatory factor 4) and forkhead box protein 1 (FOXP1) are strongly expressed by most patients, which helps distinguish it from other forms of CBCL.

Treatment

Diffuse large B-cell lymphoma, leg type is a relatively aggressive form of CBCL that requires more aggressive treatment than the conservative watchful waiting of some of the more indolent forms of primary CBCL. One regimen involves using cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab. Local chemotherapy or radiation with rituximab is another treatment option.^1,2 In patients with severe comorbidities, rituximab alone may be administered. The prognosis for DLBCLLT is not as favorable as other types of primary CBCL, with an estimated 5-year survival rate of approximately 50%.²

Differential Diagnosis

Lymphomas are malignancies of the lymphocytes that may be subdivided depending on the organ of origin. Both primary nodal lymphomas and primary cutaneous lymphomas exist. Primary nodal lymphomas arise from the lymph nodes and are divided into Hodgkin and non-Hodgkin lymphomas. There are 2 major types of primary cutaneous lymphomas: cutaneous T-cell lymphoma (CTCL) and CBCL. Most primary cutaneous lymphomas are CTCLs, accounting for 75% to 80%.³

Pseudolymphoma
Pseudolymphoma is an inflammatory condition that may histologically mimic cutaneous lymphoma but has a benign clinical course. Pseudolymphoma is not a specific disease but rather is a reactive lymphoproliferative response to a known or unknown stimulus.⁴ Pseudolymphoma can be broken down into 2 or 3 major categories: cutaneous B-cell pseudolymphoma; cutaneous T-cell pseudolymphoma; and debatably lymphomatoid papulosis, a chronic, self-remitting, papulonecrotic condition that resembles lymphoma histologically but clinically appears benign. It is unknown if lymphomatoid papulosis represents a pseudolymphoma or a true lymphoma. Lymphomatoid papulosis may represent an early indolent form of CTCL.⁴

Pseudolymphomas can be triggered by a variety of causes. Most cases are idiopathic, and a causative stimulus is never identified. Drugs are known to cause many cases of pseudolymphoma, either by a causing a hypersensitivity reaction or by depressing immunosurveillance.⁵ Pseudolymphomas may result from exogenous stimuli such as jewelry, tattoo dyes, injectable fillers (eg, silicone), insect bites, vaccines, and trauma.^6,7 Lastly, infections in the form of Borrelia, varicella, and molluscum contagiosum can potentially cause pseudolymphomas.⁴

Clinically, pseudolymphomas may demonstrate a B-cell or T-cell pattern. In cutaneous B-cell pseudolymphomas, asymptomatic solitary erythematous, violaceous, or flesh-colored nodules appear on the face, followed by the chest and arms. Cutaneous T-cell pseudolymphomas present with erythematous patches that are more likely to be symptomatic.⁴

Histologically, pseudolymphomas also are classified as demonstrating B-cell or T-cell patterns. The nodular inflammatory infiltrate of cutaneous B-cell pseudolymphoma corresponds with its clinically apparent nodules. It can be distinguished from lymphoma in that it is not solely a lymphocytic infiltrate but rather a mixed infiltrate including histiocytes, lymphocytes, eosinophils, and plasma cells. Additionally, cutaneous B-cell pseudolymphoma does not penetrate the dermis as deeply as CBCL.⁸ Cutaneous T-cell pseudolymphoma is more difficult to distinguish from CTCL because it also demonstrates a bandlike lymphocytic infiltrate in the papillary dermis with epidermotropism.⁹

Treatment must address the underlying cause of pseudolymphoma for resolution. Other treatment options include surgery, cryotherapy, local radiotherapy, topical steroids, and topical immunomodulators. Spontaneous resolution also can occur. The prognosis is better when a known trigger is eliminated, though idiopathic pseudolymphomas may be chronic in nature. It is important to rule out concurrent cutaneous lymphoma or rare transformation into cutaneous lymphoma.

Cutaneous T-Cell Lymphoma
Cutaneous T-cell lymphomas are a diverse group of neoplasms that account for most cutaneous lymphomas seen by dermatologists. In 1806, the first case of CTCL in the form of mycosis fungoides (MF) was described by Jean Louis Alibert. Mycosis fungoides represents the most common form of CTCL, accounting for approximately 50% of all primary cutaneous lymphomas.¹⁰ Mycosis fungoides was named after its morphological resemblance to mushrooms. Although not all cases exhibit a classic progression, MF is known for its stepwise progression from patch stage to tumor stage.

Clinically, lesions typically begin as patches that progress to plaques and finally tumors. This progression may not always occur and often can take years to decades to progress. Patches are characterized by erythematous, finely scaling lesions that may be easily confused with eczema or psoriasis. Lesions occur primarily in a swimming trunk distribution.

Mycosis fungoides histologically demonstrates a bandlike lymphocytic infiltrate with epidermotropism, which occurs when lymphocytes infiltrate the epidermis without spongiosis. These lymphocytes are larger, darker, and more angulated than normal lymphocytes. Intraepidermal nests of these atypical lymphocytes creating Pautrier microabscesses may be present. Tumor-stage lesions demonstrate diminished epidermotropism with dense sheets of lymphocytes in the dermis, and fat cells with cerebriform nuclei are present.

Therapies for MF may control the disease but may not prolong patients’ lives. Topical corticosteroids, phototherapy, and radiotherapy are options for skin-targeting therapies. Systemic chemotherapy and biological response modifiers also are viable treatment options. Prognosis for MF is poor.

There are a few notable variants of MF that are important to consider. Sézary syndrome is an erythrodermic variant of MF characterized by atypical Sézary cells. Clinically, it presents with generalized erythroderma with leonine facies, facial edema, and alopecia with associated symptoms of burning and pruritus. Histologically, Sézary syndrome is similar to MF with an increased CD4:CD8 ratio.¹⁰ Sézary syndrome may be treated with methotrexate or photopheresis, but the prognosis remains poor with an average survival of 5 years.

Cutaneous B-Cell Lymphoma
There are 5 types of primary CBCL: primary cutaneous follicle center lymphoma; primary cutaneous marginal zone B-cell lymphoma; primary cutaneous diffuse large B-cell lymphoma, other; precursor B-cell lymphoblastic lymphoma; and primary cutaneous DLBCLLT, which was seen in our patient.¹¹

Primary cutaneous follicle center lymphoma is an indolent neoplastic proliferation in the skin. Clinically, it presents with solitary or grouped pinkish purple papules, plaques, or nodules on the trunk with surrounding patches of erythema.³ Lesions located on the back are referred to as Crosti lymphoma. Histopathology reveals a lymphocytic infiltrate with a diffuse follicular pattern and large round centroblasts, centrocytes, and immunoblasts with epidermal sparing. Tumor cells stain positively for κ or λ light chains, as well as CD20, CD79a, and B-cell lymphoma 6 (BCL-6); however, staining for the protein product of BCL-2 may be negative, which differentiates this form of CBCL from primary nodal B-cell lymphoma. Staining for MUM-1 may be negative, which contrasts with the strong expression seen in DLBCLLT. The follicular pattern of follicle center lymphoma stains positive for CD10, but the diffuse pattern may be CD10 negative. The prognosis for primary cutaneous follicle center lymphoma is favorable, but the recurrence rate is up to 50%.³ Treatment includes local radiotherapy or surgical excision.

Primary cutaneous marginal zone B-cell lymphoma is another indolent primary CBCL subtype that is closely related to mucosa-associated lymphoid tissue lymphomas and arises in areas of acrodermatitis chronica atrophicans and Borrelia infection. Clinically, it presents with recurrent, asymptomatic, red-brown papules, plaques, and nodules of the arms and legs. Histologically, there is a patchy infiltrate in the dermis and subcutis with sparing of the epidermis with pale-staining cells with indented nuclei, along with plasma cells and eosinophils. Primary cutaneous marginal zone B-cell lymphoma typically does not demonstrate epidermotropism. Centrocyte cells stain positively for CD20, CD79a, and BCL-2. The prognosis of primary cutaneous marginal zone B-cell lymphoma is favorable. Treatment is similar to primary cutaneous follicle center lymphoma with surgical excision, radiotherapy, and surveillance being the main modalities.

Primary cutaneous diffuse large B-cell lymphoma, other is an intermediately aggressive form of primary CBCL that is thought to be related to primary cutaneous DLBCLLT. Clinically, it presents with indurated erythematous to violaceous plaques on the trunk and thighs that may resemble a vascular tumor or panniculitis.^2,12 Histopathologically, this form of lymphoma presents with a round cell morphology without BCL-2 expression, which distinguishes it from DLBCLLT. If limited to skin, the prognosis is better than the systemic form but is still less favorable than other forms of CBCL.

Precursor B-cell lymphoblastic lymphoma is an extremely rare type of CBCL that potentially can occur in the skin. It primarily affects children and young adults. Clinically, it presents as a solitary large erythematous tumor of the head. Histologically, monomorphic proliferation of medium-sized cells with round nuclei that demonstrate a starry sky pattern with multiple mitotic cells can be observed.¹³ Immunohistochemical markers such as CD43, CD10, CD20, and CD79a may be positive. The disease is very aggressive with poor prognosis if left untreated.

CONCLUSION

We present a rare case of primary cutaneous DLBCLLT. Our case demonstrates the classic presentation of primary cutaneous DLBCLLT in a 74-year-old woman with a tumor on the lower left leg. Histologically, a dense dermal and subcutis infiltrate of centroblasts and immunoblasts with a grenz zone was present. Immunostaining in our patient was consistent with characteristic findings in the literature, staining highly positive for BCL-2 and MUM-1. Primary cutaneous DLBCLLT is an extremely rare and unique form of cutaneous lymphoma that can have potentially fatal consequences if undiagnosed; therefore, clinicians must take great care to make the correct diagnosis based on a knowledge of the clinical and immunohistochemical findings of DLBCLLT.

CASE REPORT

A 74-year-old woman presented with a painful lesion on the left lower leg that was getting larger and more edematous and erythematous over the last 5 months. She experienced numbness and burning of the left lower leg 1 year prior to the development of the lesion. A review of her medical history revealed an otherwise healthy woman with no constitutional symptoms of fever, chills, nausea, vomiting, diarrhea, or chest pain. The patient did not exhibit mucosal, genital, or nail involvement. Physical examination revealed a group of four 1-cm, ill-defined, irregularly bordered, violaceous plaques on the left anterior tibial leg with faint surrounding erythematous to violaceous patches (Figure 1). The plaques were tender to palpation with no bleeding or drainage.

ct102002031_e_fig1.png

An 8.0-mm punch biopsy of the lesion was obtained. Hematoxylin and eosin staining on low-power magnification demonstrated a diffuse lymphocytic inflammatory infiltrate in the dermis and subcutis. Notable sparing of the subepidermal area (free grenz zone) was present (Figure 2A). On higher power, centroblasts and immunoblasts were visualized alongside extravasated red blood cells (Figure 2B). A diagnosis of primary cutaneous diffuse large B-cell lymphoma, leg type (DLBCLLT) was made. Various immunohistochemical stains confirmed the diagnosis, including B-cell lymphoma 2 (BCL-2)(Figure 3A) and multiple myeloma oncogene 1 (MUM-1)(Figure 3B), which were highly positive in our patient. The patient had a negative bone marrow biopsy and positron emission tomography scan. She was started on rituximab infusions and multiple radiation treatments. At 2-year follow-up the lymphoma continued to recur despite radiation therapy.

ct102002031_e_fig2.png

ct102002031_e_fig3.png

COMMENT

Incidence and Clinical Characteristics

Primary cutaneous DLBCLLT is an intermediately aggressive form of primary cutaneous B-cell lymphoma (CBCL) that accounts for approximately 10% to 20% of all primary CBCLs and 1% to 3% of all cutaneous lymphomas.¹ Diffuse large B-cell lymphoma, leg type primarily affects elderly patients (median age, 70 years). Women are more commonly affected. Clinically, primary cutaneous DLBCLLT presents as red-brown to bluish nodules or tumors on one or both distal legs. Although referred to as leg-type diffuse large B-cell lymphoma, 10% to 15% of patients have lesions in anatomic areas other than the legs, most commonly the trunk.

Histopathology

The diagnosis of DLBCLLT is best made histologically. There is a dense inflammatory infiltrate present in the dermis and subcutis that may extend upward into the dermoepidermal junction. Often a subepidermal free grenz zone may be seen, and adnexal structures may be destroyed. This infiltrate is composed of confluent sheets of large round cells including centroblasts and immunoblasts.² Centroblasts are large cells that have nuclei with several small nucleoli adhering to the membrane, while immunoblasts are large round cells containing nuclei with large central nucleoli. Both centroblasts and immunoblasts stain positively for BCL-2. Centrocytes typically are absent. Staining for BCL-2 can be important in distinguishing DLBCLLT from other forms of CBCL. Diffuse large B-cell lymphoma, leg type also can demonstrate clusters of large atypical cells in the epidermis simulating epidermotropism and Pautrier microabscesses. Neoplastic cells in this condition may express monoclonal surface and cytoplasmic immunoglobulins. Primary cutaneous DLBCLLT typically is positive for B-cell markers CD20 and CD79a. Additionally, MUM-1/IRF4 (interferon regulatory factor 4) and forkhead box protein 1 (FOXP1) are strongly expressed by most patients, which helps distinguish it from other forms of CBCL.

Treatment

Diffuse large B-cell lymphoma, leg type is a relatively aggressive form of CBCL that requires more aggressive treatment than the conservative watchful waiting of some of the more indolent forms of primary CBCL. One regimen involves using cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab. Local chemotherapy or radiation with rituximab is another treatment option.^1,2 In patients with severe comorbidities, rituximab alone may be administered. The prognosis for DLBCLLT is not as favorable as other types of primary CBCL, with an estimated 5-year survival rate of approximately 50%.²

Differential Diagnosis

Lymphomas are malignancies of the lymphocytes that may be subdivided depending on the organ of origin. Both primary nodal lymphomas and primary cutaneous lymphomas exist. Primary nodal lymphomas arise from the lymph nodes and are divided into Hodgkin and non-Hodgkin lymphomas. There are 2 major types of primary cutaneous lymphomas: cutaneous T-cell lymphoma (CTCL) and CBCL. Most primary cutaneous lymphomas are CTCLs, accounting for 75% to 80%.³

Pseudolymphoma
Pseudolymphoma is an inflammatory condition that may histologically mimic cutaneous lymphoma but has a benign clinical course. Pseudolymphoma is not a specific disease but rather is a reactive lymphoproliferative response to a known or unknown stimulus.⁴ Pseudolymphoma can be broken down into 2 or 3 major categories: cutaneous B-cell pseudolymphoma; cutaneous T-cell pseudolymphoma; and debatably lymphomatoid papulosis, a chronic, self-remitting, papulonecrotic condition that resembles lymphoma histologically but clinically appears benign. It is unknown if lymphomatoid papulosis represents a pseudolymphoma or a true lymphoma. Lymphomatoid papulosis may represent an early indolent form of CTCL.⁴

Pseudolymphomas can be triggered by a variety of causes. Most cases are idiopathic, and a causative stimulus is never identified. Drugs are known to cause many cases of pseudolymphoma, either by a causing a hypersensitivity reaction or by depressing immunosurveillance.⁵ Pseudolymphomas may result from exogenous stimuli such as jewelry, tattoo dyes, injectable fillers (eg, silicone), insect bites, vaccines, and trauma.^6,7 Lastly, infections in the form of Borrelia, varicella, and molluscum contagiosum can potentially cause pseudolymphomas.⁴

Clinically, pseudolymphomas may demonstrate a B-cell or T-cell pattern. In cutaneous B-cell pseudolymphomas, asymptomatic solitary erythematous, violaceous, or flesh-colored nodules appear on the face, followed by the chest and arms. Cutaneous T-cell pseudolymphomas present with erythematous patches that are more likely to be symptomatic.⁴

Histologically, pseudolymphomas also are classified as demonstrating B-cell or T-cell patterns. The nodular inflammatory infiltrate of cutaneous B-cell pseudolymphoma corresponds with its clinically apparent nodules. It can be distinguished from lymphoma in that it is not solely a lymphocytic infiltrate but rather a mixed infiltrate including histiocytes, lymphocytes, eosinophils, and plasma cells. Additionally, cutaneous B-cell pseudolymphoma does not penetrate the dermis as deeply as CBCL.⁸ Cutaneous T-cell pseudolymphoma is more difficult to distinguish from CTCL because it also demonstrates a bandlike lymphocytic infiltrate in the papillary dermis with epidermotropism.⁹

Treatment must address the underlying cause of pseudolymphoma for resolution. Other treatment options include surgery, cryotherapy, local radiotherapy, topical steroids, and topical immunomodulators. Spontaneous resolution also can occur. The prognosis is better when a known trigger is eliminated, though idiopathic pseudolymphomas may be chronic in nature. It is important to rule out concurrent cutaneous lymphoma or rare transformation into cutaneous lymphoma.

Cutaneous T-Cell Lymphoma
Cutaneous T-cell lymphomas are a diverse group of neoplasms that account for most cutaneous lymphomas seen by dermatologists. In 1806, the first case of CTCL in the form of mycosis fungoides (MF) was described by Jean Louis Alibert. Mycosis fungoides represents the most common form of CTCL, accounting for approximately 50% of all primary cutaneous lymphomas.¹⁰ Mycosis fungoides was named after its morphological resemblance to mushrooms. Although not all cases exhibit a classic progression, MF is known for its stepwise progression from patch stage to tumor stage.

Clinically, lesions typically begin as patches that progress to plaques and finally tumors. This progression may not always occur and often can take years to decades to progress. Patches are characterized by erythematous, finely scaling lesions that may be easily confused with eczema or psoriasis. Lesions occur primarily in a swimming trunk distribution.

Mycosis fungoides histologically demonstrates a bandlike lymphocytic infiltrate with epidermotropism, which occurs when lymphocytes infiltrate the epidermis without spongiosis. These lymphocytes are larger, darker, and more angulated than normal lymphocytes. Intraepidermal nests of these atypical lymphocytes creating Pautrier microabscesses may be present. Tumor-stage lesions demonstrate diminished epidermotropism with dense sheets of lymphocytes in the dermis, and fat cells with cerebriform nuclei are present.

Therapies for MF may control the disease but may not prolong patients’ lives. Topical corticosteroids, phototherapy, and radiotherapy are options for skin-targeting therapies. Systemic chemotherapy and biological response modifiers also are viable treatment options. Prognosis for MF is poor.

There are a few notable variants of MF that are important to consider. Sézary syndrome is an erythrodermic variant of MF characterized by atypical Sézary cells. Clinically, it presents with generalized erythroderma with leonine facies, facial edema, and alopecia with associated symptoms of burning and pruritus. Histologically, Sézary syndrome is similar to MF with an increased CD4:CD8 ratio.¹⁰ Sézary syndrome may be treated with methotrexate or photopheresis, but the prognosis remains poor with an average survival of 5 years.

Cutaneous B-Cell Lymphoma
There are 5 types of primary CBCL: primary cutaneous follicle center lymphoma; primary cutaneous marginal zone B-cell lymphoma; primary cutaneous diffuse large B-cell lymphoma, other; precursor B-cell lymphoblastic lymphoma; and primary cutaneous DLBCLLT, which was seen in our patient.¹¹

Primary cutaneous follicle center lymphoma is an indolent neoplastic proliferation in the skin. Clinically, it presents with solitary or grouped pinkish purple papules, plaques, or nodules on the trunk with surrounding patches of erythema.³ Lesions located on the back are referred to as Crosti lymphoma. Histopathology reveals a lymphocytic infiltrate with a diffuse follicular pattern and large round centroblasts, centrocytes, and immunoblasts with epidermal sparing. Tumor cells stain positively for κ or λ light chains, as well as CD20, CD79a, and B-cell lymphoma 6 (BCL-6); however, staining for the protein product of BCL-2 may be negative, which differentiates this form of CBCL from primary nodal B-cell lymphoma. Staining for MUM-1 may be negative, which contrasts with the strong expression seen in DLBCLLT. The follicular pattern of follicle center lymphoma stains positive for CD10, but the diffuse pattern may be CD10 negative. The prognosis for primary cutaneous follicle center lymphoma is favorable, but the recurrence rate is up to 50%.³ Treatment includes local radiotherapy or surgical excision.

Primary cutaneous marginal zone B-cell lymphoma is another indolent primary CBCL subtype that is closely related to mucosa-associated lymphoid tissue lymphomas and arises in areas of acrodermatitis chronica atrophicans and Borrelia infection. Clinically, it presents with recurrent, asymptomatic, red-brown papules, plaques, and nodules of the arms and legs. Histologically, there is a patchy infiltrate in the dermis and subcutis with sparing of the epidermis with pale-staining cells with indented nuclei, along with plasma cells and eosinophils. Primary cutaneous marginal zone B-cell lymphoma typically does not demonstrate epidermotropism. Centrocyte cells stain positively for CD20, CD79a, and BCL-2. The prognosis of primary cutaneous marginal zone B-cell lymphoma is favorable. Treatment is similar to primary cutaneous follicle center lymphoma with surgical excision, radiotherapy, and surveillance being the main modalities.

Primary cutaneous diffuse large B-cell lymphoma, other is an intermediately aggressive form of primary CBCL that is thought to be related to primary cutaneous DLBCLLT. Clinically, it presents with indurated erythematous to violaceous plaques on the trunk and thighs that may resemble a vascular tumor or panniculitis.^2,12 Histopathologically, this form of lymphoma presents with a round cell morphology without BCL-2 expression, which distinguishes it from DLBCLLT. If limited to skin, the prognosis is better than the systemic form but is still less favorable than other forms of CBCL.

Precursor B-cell lymphoblastic lymphoma is an extremely rare type of CBCL that potentially can occur in the skin. It primarily affects children and young adults. Clinically, it presents as a solitary large erythematous tumor of the head. Histologically, monomorphic proliferation of medium-sized cells with round nuclei that demonstrate a starry sky pattern with multiple mitotic cells can be observed.¹³ Immunohistochemical markers such as CD43, CD10, CD20, and CD79a may be positive. The disease is very aggressive with poor prognosis if left untreated.

CONCLUSION

We present a rare case of primary cutaneous DLBCLLT. Our case demonstrates the classic presentation of primary cutaneous DLBCLLT in a 74-year-old woman with a tumor on the lower left leg. Histologically, a dense dermal and subcutis infiltrate of centroblasts and immunoblasts with a grenz zone was present. Immunostaining in our patient was consistent with characteristic findings in the literature, staining highly positive for BCL-2 and MUM-1. Primary cutaneous DLBCLLT is an extremely rare and unique form of cutaneous lymphoma that can have potentially fatal consequences if undiagnosed; therefore, clinicians must take great care to make the correct diagnosis based on a knowledge of the clinical and immunohistochemical findings of DLBCLLT.

CASE REPORT

A 74-year-old woman presented with a painful lesion on the left lower leg that was getting larger and more edematous and erythematous over the last 5 months. She experienced numbness and burning of the left lower leg 1 year prior to the development of the lesion. A review of her medical history revealed an otherwise healthy woman with no constitutional symptoms of fever, chills, nausea, vomiting, diarrhea, or chest pain. The patient did not exhibit mucosal, genital, or nail involvement. Physical examination revealed a group of four 1-cm, ill-defined, irregularly bordered, violaceous plaques on the left anterior tibial leg with faint surrounding erythematous to violaceous patches (Figure 1). The plaques were tender to palpation with no bleeding or drainage.

ct102002031_e_fig1.png

An 8.0-mm punch biopsy of the lesion was obtained. Hematoxylin and eosin staining on low-power magnification demonstrated a diffuse lymphocytic inflammatory infiltrate in the dermis and subcutis. Notable sparing of the subepidermal area (free grenz zone) was present (Figure 2A). On higher power, centroblasts and immunoblasts were visualized alongside extravasated red blood cells (Figure 2B). A diagnosis of primary cutaneous diffuse large B-cell lymphoma, leg type (DLBCLLT) was made. Various immunohistochemical stains confirmed the diagnosis, including B-cell lymphoma 2 (BCL-2)(Figure 3A) and multiple myeloma oncogene 1 (MUM-1)(Figure 3B), which were highly positive in our patient. The patient had a negative bone marrow biopsy and positron emission tomography scan. She was started on rituximab infusions and multiple radiation treatments. At 2-year follow-up the lymphoma continued to recur despite radiation therapy.

ct102002031_e_fig2.png

ct102002031_e_fig3.png

COMMENT

Incidence and Clinical Characteristics

Primary cutaneous DLBCLLT is an intermediately aggressive form of primary cutaneous B-cell lymphoma (CBCL) that accounts for approximately 10% to 20% of all primary CBCLs and 1% to 3% of all cutaneous lymphomas.¹ Diffuse large B-cell lymphoma, leg type primarily affects elderly patients (median age, 70 years). Women are more commonly affected. Clinically, primary cutaneous DLBCLLT presents as red-brown to bluish nodules or tumors on one or both distal legs. Although referred to as leg-type diffuse large B-cell lymphoma, 10% to 15% of patients have lesions in anatomic areas other than the legs, most commonly the trunk.

Histopathology

The diagnosis of DLBCLLT is best made histologically. There is a dense inflammatory infiltrate present in the dermis and subcutis that may extend upward into the dermoepidermal junction. Often a subepidermal free grenz zone may be seen, and adnexal structures may be destroyed. This infiltrate is composed of confluent sheets of large round cells including centroblasts and immunoblasts.² Centroblasts are large cells that have nuclei with several small nucleoli adhering to the membrane, while immunoblasts are large round cells containing nuclei with large central nucleoli. Both centroblasts and immunoblasts stain positively for BCL-2. Centrocytes typically are absent. Staining for BCL-2 can be important in distinguishing DLBCLLT from other forms of CBCL. Diffuse large B-cell lymphoma, leg type also can demonstrate clusters of large atypical cells in the epidermis simulating epidermotropism and Pautrier microabscesses. Neoplastic cells in this condition may express monoclonal surface and cytoplasmic immunoglobulins. Primary cutaneous DLBCLLT typically is positive for B-cell markers CD20 and CD79a. Additionally, MUM-1/IRF4 (interferon regulatory factor 4) and forkhead box protein 1 (FOXP1) are strongly expressed by most patients, which helps distinguish it from other forms of CBCL.

Treatment

Diffuse large B-cell lymphoma, leg type is a relatively aggressive form of CBCL that requires more aggressive treatment than the conservative watchful waiting of some of the more indolent forms of primary CBCL. One regimen involves using cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab. Local chemotherapy or radiation with rituximab is another treatment option.^1,2 In patients with severe comorbidities, rituximab alone may be administered. The prognosis for DLBCLLT is not as favorable as other types of primary CBCL, with an estimated 5-year survival rate of approximately 50%.²

Differential Diagnosis

Lymphomas are malignancies of the lymphocytes that may be subdivided depending on the organ of origin. Both primary nodal lymphomas and primary cutaneous lymphomas exist. Primary nodal lymphomas arise from the lymph nodes and are divided into Hodgkin and non-Hodgkin lymphomas. There are 2 major types of primary cutaneous lymphomas: cutaneous T-cell lymphoma (CTCL) and CBCL. Most primary cutaneous lymphomas are CTCLs, accounting for 75% to 80%.³

Pseudolymphoma
Pseudolymphoma is an inflammatory condition that may histologically mimic cutaneous lymphoma but has a benign clinical course. Pseudolymphoma is not a specific disease but rather is a reactive lymphoproliferative response to a known or unknown stimulus.⁴ Pseudolymphoma can be broken down into 2 or 3 major categories: cutaneous B-cell pseudolymphoma; cutaneous T-cell pseudolymphoma; and debatably lymphomatoid papulosis, a chronic, self-remitting, papulonecrotic condition that resembles lymphoma histologically but clinically appears benign. It is unknown if lymphomatoid papulosis represents a pseudolymphoma or a true lymphoma. Lymphomatoid papulosis may represent an early indolent form of CTCL.⁴

Pseudolymphomas can be triggered by a variety of causes. Most cases are idiopathic, and a causative stimulus is never identified. Drugs are known to cause many cases of pseudolymphoma, either by a causing a hypersensitivity reaction or by depressing immunosurveillance.⁵ Pseudolymphomas may result from exogenous stimuli such as jewelry, tattoo dyes, injectable fillers (eg, silicone), insect bites, vaccines, and trauma.^6,7 Lastly, infections in the form of Borrelia, varicella, and molluscum contagiosum can potentially cause pseudolymphomas.⁴

Clinically, pseudolymphomas may demonstrate a B-cell or T-cell pattern. In cutaneous B-cell pseudolymphomas, asymptomatic solitary erythematous, violaceous, or flesh-colored nodules appear on the face, followed by the chest and arms. Cutaneous T-cell pseudolymphomas present with erythematous patches that are more likely to be symptomatic.⁴

Histologically, pseudolymphomas also are classified as demonstrating B-cell or T-cell patterns. The nodular inflammatory infiltrate of cutaneous B-cell pseudolymphoma corresponds with its clinically apparent nodules. It can be distinguished from lymphoma in that it is not solely a lymphocytic infiltrate but rather a mixed infiltrate including histiocytes, lymphocytes, eosinophils, and plasma cells. Additionally, cutaneous B-cell pseudolymphoma does not penetrate the dermis as deeply as CBCL.⁸ Cutaneous T-cell pseudolymphoma is more difficult to distinguish from CTCL because it also demonstrates a bandlike lymphocytic infiltrate in the papillary dermis with epidermotropism.⁹

Treatment must address the underlying cause of pseudolymphoma for resolution. Other treatment options include surgery, cryotherapy, local radiotherapy, topical steroids, and topical immunomodulators. Spontaneous resolution also can occur. The prognosis is better when a known trigger is eliminated, though idiopathic pseudolymphomas may be chronic in nature. It is important to rule out concurrent cutaneous lymphoma or rare transformation into cutaneous lymphoma.

Cutaneous T-Cell Lymphoma
Cutaneous T-cell lymphomas are a diverse group of neoplasms that account for most cutaneous lymphomas seen by dermatologists. In 1806, the first case of CTCL in the form of mycosis fungoides (MF) was described by Jean Louis Alibert. Mycosis fungoides represents the most common form of CTCL, accounting for approximately 50% of all primary cutaneous lymphomas.¹⁰ Mycosis fungoides was named after its morphological resemblance to mushrooms. Although not all cases exhibit a classic progression, MF is known for its stepwise progression from patch stage to tumor stage.

Clinically, lesions typically begin as patches that progress to plaques and finally tumors. This progression may not always occur and often can take years to decades to progress. Patches are characterized by erythematous, finely scaling lesions that may be easily confused with eczema or psoriasis. Lesions occur primarily in a swimming trunk distribution.

Mycosis fungoides histologically demonstrates a bandlike lymphocytic infiltrate with epidermotropism, which occurs when lymphocytes infiltrate the epidermis without spongiosis. These lymphocytes are larger, darker, and more angulated than normal lymphocytes. Intraepidermal nests of these atypical lymphocytes creating Pautrier microabscesses may be present. Tumor-stage lesions demonstrate diminished epidermotropism with dense sheets of lymphocytes in the dermis, and fat cells with cerebriform nuclei are present.

Therapies for MF may control the disease but may not prolong patients’ lives. Topical corticosteroids, phototherapy, and radiotherapy are options for skin-targeting therapies. Systemic chemotherapy and biological response modifiers also are viable treatment options. Prognosis for MF is poor.

There are a few notable variants of MF that are important to consider. Sézary syndrome is an erythrodermic variant of MF characterized by atypical Sézary cells. Clinically, it presents with generalized erythroderma with leonine facies, facial edema, and alopecia with associated symptoms of burning and pruritus. Histologically, Sézary syndrome is similar to MF with an increased CD4:CD8 ratio.¹⁰ Sézary syndrome may be treated with methotrexate or photopheresis, but the prognosis remains poor with an average survival of 5 years.

Cutaneous B-Cell Lymphoma
There are 5 types of primary CBCL: primary cutaneous follicle center lymphoma; primary cutaneous marginal zone B-cell lymphoma; primary cutaneous diffuse large B-cell lymphoma, other; precursor B-cell lymphoblastic lymphoma; and primary cutaneous DLBCLLT, which was seen in our patient.¹¹

Primary cutaneous follicle center lymphoma is an indolent neoplastic proliferation in the skin. Clinically, it presents with solitary or grouped pinkish purple papules, plaques, or nodules on the trunk with surrounding patches of erythema.³ Lesions located on the back are referred to as Crosti lymphoma. Histopathology reveals a lymphocytic infiltrate with a diffuse follicular pattern and large round centroblasts, centrocytes, and immunoblasts with epidermal sparing. Tumor cells stain positively for κ or λ light chains, as well as CD20, CD79a, and B-cell lymphoma 6 (BCL-6); however, staining for the protein product of BCL-2 may be negative, which differentiates this form of CBCL from primary nodal B-cell lymphoma. Staining for MUM-1 may be negative, which contrasts with the strong expression seen in DLBCLLT. The follicular pattern of follicle center lymphoma stains positive for CD10, but the diffuse pattern may be CD10 negative. The prognosis for primary cutaneous follicle center lymphoma is favorable, but the recurrence rate is up to 50%.³ Treatment includes local radiotherapy or surgical excision.

Primary cutaneous marginal zone B-cell lymphoma is another indolent primary CBCL subtype that is closely related to mucosa-associated lymphoid tissue lymphomas and arises in areas of acrodermatitis chronica atrophicans and Borrelia infection. Clinically, it presents with recurrent, asymptomatic, red-brown papules, plaques, and nodules of the arms and legs. Histologically, there is a patchy infiltrate in the dermis and subcutis with sparing of the epidermis with pale-staining cells with indented nuclei, along with plasma cells and eosinophils. Primary cutaneous marginal zone B-cell lymphoma typically does not demonstrate epidermotropism. Centrocyte cells stain positively for CD20, CD79a, and BCL-2. The prognosis of primary cutaneous marginal zone B-cell lymphoma is favorable. Treatment is similar to primary cutaneous follicle center lymphoma with surgical excision, radiotherapy, and surveillance being the main modalities.

Primary cutaneous diffuse large B-cell lymphoma, other is an intermediately aggressive form of primary CBCL that is thought to be related to primary cutaneous DLBCLLT. Clinically, it presents with indurated erythematous to violaceous plaques on the trunk and thighs that may resemble a vascular tumor or panniculitis.^2,12 Histopathologically, this form of lymphoma presents with a round cell morphology without BCL-2 expression, which distinguishes it from DLBCLLT. If limited to skin, the prognosis is better than the systemic form but is still less favorable than other forms of CBCL.

Precursor B-cell lymphoblastic lymphoma is an extremely rare type of CBCL that potentially can occur in the skin. It primarily affects children and young adults. Clinically, it presents as a solitary large erythematous tumor of the head. Histologically, monomorphic proliferation of medium-sized cells with round nuclei that demonstrate a starry sky pattern with multiple mitotic cells can be observed.¹³ Immunohistochemical markers such as CD43, CD10, CD20, and CD79a may be positive. The disease is very aggressive with poor prognosis if left untreated.

CONCLUSION

We present a rare case of primary cutaneous DLBCLLT. Our case demonstrates the classic presentation of primary cutaneous DLBCLLT in a 74-year-old woman with a tumor on the lower left leg. Histologically, a dense dermal and subcutis infiltrate of centroblasts and immunoblasts with a grenz zone was present. Immunostaining in our patient was consistent with characteristic findings in the literature, staining highly positive for BCL-2 and MUM-1. Primary cutaneous DLBCLLT is an extremely rare and unique form of cutaneous lymphoma that can have potentially fatal consequences if undiagnosed; therefore, clinicians must take great care to make the correct diagnosis based on a knowledge of the clinical and immunohistochemical findings of DLBCLLT.

To the Editor:
Collagenous and elastotic marginal plaques of the hands (CEMPHs) has several names including degenerative collagenous plaques of the hands, keratoelastoidosis marginalis, and digital papular calcific elastosis. This rare disorder is an acquired, slowly progressive, asymptomatic, dermal connective tissue abnormality that is underrecognized and underdiagnosed. Clinical presentation includes hyperkeratotic translucent papules arranged linearly on the radial aspect of the hands.

A 74-year-old woman described having "rough hands" of more than 20 years' duration. She presented with 4-cm wide longitudinal, erythematous, firm, depressed plaques along the lateral edge of the second finger and extending to the medial thumb in both hands (Figure 1). She had attempted multiple treatments by her primary care physician, including topical and oral medications unknown to the patient and light therapy, all without benefit over a period of several years. We have attempted salicylic acid 40%, clobetasol cream 0.05%, and emollient creams containing α-hydroxy acid. At best the condition fluctuated between a subtle raised scale at the edge to smooth and occasionally more red-pink, seemingly unrelated to any treatments.

ct099003025_e_fig1.png

The patient did not have plaques elsewhere on the body, and notably, the feet were clear. She did not have a history of repeated trauma to the hands and did not engage in manual labor. She denied excessive sun exposure, though she had Fitzpatrick skin type III and a history of multiple precancers and nonmelanoma skin cancers 7 years prior to presentation.

Histology of CEMPH reveals a hyperkeratotic epidermis with an avascular and acellular replacement of the superficial reticular dermis by haphazardly arranged, thickened collagen fibers (Figure 2A-2C). Collagen fibers were oriented perpendicularly to the epidermal surface. Intervening amorphous basophilic elastotic masses were present in the upper dermis with occasional calcification and degenerative elastic fibers (Figure 2D).

ct099003025_e_fig.png

Collagenous and elastotic marginal plaques of the hands is a chronic, asymptomatic, sclerotic skin disorder described in a 1960 case series of 5 patients reported by Burks et al.¹ Although it has many names, the most common is CEMPH. Collagenous and elastotic marginal plaques of the hands most often presents in white men aged 50 to 60 years.² Patients typically are asymptomatic with plaques limited to the junction of the palmar and dorsal surfaces of the hands with only minimal intermittent stiffness around the flexor creases. Lesions begin as discrete yellow papules that coalesce to form hyperkeratotic linear plaques with occasional telangiectasia.³

The etiology of CEMPH is attributed to collagen and elastin degeneration by chronic actinic damage, pressure, or trauma.^4,5 The 3 stages of degeneration include an initial linear padded stage, an intermediate padded plaque stage, and an advanced padded hyperkeratotic plaque stage.⁴ Vascular compromise is seen from the enlarged and fused thickened collagen and elastic fibers that in turn lead to ischemic changes, hyperkeratosis with epidermal atrophy, and papillary dermis telangiectasia. Absence or weak expression of keratins 14 and 10 and strong expression of keratin 16 have been reported in the epidermis of CEMPH patients.⁴

Collagenous and elastotic marginal plaques of the hands do not have a specific treatment, as it is a benign, slowly progressive condition. Several treatments such as laser therapy, high-potency topical corticosteroids, topical tazarotene and tretinoin, oral isotretinoin, and cryotherapy have been tried with little long-term success.⁴ Moisturizing may help reduce fissuring, and patients are advised to avoid the sun and repeated trauma to the hands.

The differential diagnosis of CEMPH is summarized in the Table. Two genodermatoses—acrokeratoelastoidosis of Costa and focal acral hyperkeratosis—clinically resemble CEMPH. Acrokeratoelastoidosis of Costa is an autosomal-dominant condition that occurs without trauma in children and young adults. Histopathology shows orthokeratotic hyperkeratosis due to an overproduction of filaggrin in the granular layer of the epidermis. The reticular dermis shows basophilic, thick, curled and fragmented elastic fibers with dilated capillaries that can be seen with Weigert elastic, Verhoeff-van Gieson, or orcein stains. Focal acral hyperkeratosis occurs on the hands and feet, predominantly in black patients. On histology, the epidermis shows a characteristic orthohyperkeratosis, moderate acanthosis, and slight hypergranulosis with no dermal involvment.⁶

CT099003025_e_Table.JPG

Chronic hyperkeratotic eczematous dermatitis is another common entity in the differential characterized by hyperkeratotic plaques that scale and fissure. Biopsy demonstrates a spongiotic acanthotic epidermis.^7,8

Psoriasis of the hands, specifically hyperkeratotic palmoplantar psoriasis, is associated with manual labor, similar to CEMPH. Histology shows epidermal hyperplasia; regular acanthosis; loss of the granular skin layer with prominent dermal capillaries; and a mixed dermal infiltrate of lymphocytes, macrophages, and neutrophils.⁹ Hyperkeratotic palmoplantar lichen planus presents with pruritic papules in the third and fifth decades of life. Histologically, hyperkeratosis, acanthosis, and wedge-shaped hypergranulosis with a lichenoid lymphocytic infiltration at the dermoepidermal junction is seen.¹⁰

Palmoplantar keratodermas due to inflammatory reactive dermatoses include callosities that develop in response to repeated trauma or friction on the skin. On histology, there is prominent hyperkeratosis and acanthosis with moderate papillomatosis.¹¹ Drug-related palmoplantar keratodermas such as those from arsenic exposure can lead to multiple, irregular, verrucous, keratotic, and pigmented lesions on the palms and soles. Histologically, atypical keratinocytes are seen in the epidermis with thick hyperkeratosis and vacuolated cells without solar elastosis.¹²

In conclusion, CEMPH is an underdiagnosed and underrecognized condition characterized by asymptomatic hyperkeratotic linear plaques along the medial aspect of the thumb and radial aspect of the index finger. It is important to keep CEMPH in mind when dealing with occupational cases of repeated long-term trauma or pressure to the hands as well as excessive sun exposure. It also is imperative to separate it from other diseases and avoid misdiagnosing this degenerative collagenous and elastotic disease as a malignant lesion. 

To the Editor:
Collagenous and elastotic marginal plaques of the hands (CEMPHs) has several names including degenerative collagenous plaques of the hands, keratoelastoidosis marginalis, and digital papular calcific elastosis. This rare disorder is an acquired, slowly progressive, asymptomatic, dermal connective tissue abnormality that is underrecognized and underdiagnosed. Clinical presentation includes hyperkeratotic translucent papules arranged linearly on the radial aspect of the hands.

A 74-year-old woman described having "rough hands" of more than 20 years' duration. She presented with 4-cm wide longitudinal, erythematous, firm, depressed plaques along the lateral edge of the second finger and extending to the medial thumb in both hands (Figure 1). She had attempted multiple treatments by her primary care physician, including topical and oral medications unknown to the patient and light therapy, all without benefit over a period of several years. We have attempted salicylic acid 40%, clobetasol cream 0.05%, and emollient creams containing α-hydroxy acid. At best the condition fluctuated between a subtle raised scale at the edge to smooth and occasionally more red-pink, seemingly unrelated to any treatments.

ct099003025_e_fig1.png

The patient did not have plaques elsewhere on the body, and notably, the feet were clear. She did not have a history of repeated trauma to the hands and did not engage in manual labor. She denied excessive sun exposure, though she had Fitzpatrick skin type III and a history of multiple precancers and nonmelanoma skin cancers 7 years prior to presentation.

Histology of CEMPH reveals a hyperkeratotic epidermis with an avascular and acellular replacement of the superficial reticular dermis by haphazardly arranged, thickened collagen fibers (Figure 2A-2C). Collagen fibers were oriented perpendicularly to the epidermal surface. Intervening amorphous basophilic elastotic masses were present in the upper dermis with occasional calcification and degenerative elastic fibers (Figure 2D).

ct099003025_e_fig.png

Collagenous and elastotic marginal plaques of the hands is a chronic, asymptomatic, sclerotic skin disorder described in a 1960 case series of 5 patients reported by Burks et al.¹ Although it has many names, the most common is CEMPH. Collagenous and elastotic marginal plaques of the hands most often presents in white men aged 50 to 60 years.² Patients typically are asymptomatic with plaques limited to the junction of the palmar and dorsal surfaces of the hands with only minimal intermittent stiffness around the flexor creases. Lesions begin as discrete yellow papules that coalesce to form hyperkeratotic linear plaques with occasional telangiectasia.³

The etiology of CEMPH is attributed to collagen and elastin degeneration by chronic actinic damage, pressure, or trauma.^4,5 The 3 stages of degeneration include an initial linear padded stage, an intermediate padded plaque stage, and an advanced padded hyperkeratotic plaque stage.⁴ Vascular compromise is seen from the enlarged and fused thickened collagen and elastic fibers that in turn lead to ischemic changes, hyperkeratosis with epidermal atrophy, and papillary dermis telangiectasia. Absence or weak expression of keratins 14 and 10 and strong expression of keratin 16 have been reported in the epidermis of CEMPH patients.⁴

Collagenous and elastotic marginal plaques of the hands do not have a specific treatment, as it is a benign, slowly progressive condition. Several treatments such as laser therapy, high-potency topical corticosteroids, topical tazarotene and tretinoin, oral isotretinoin, and cryotherapy have been tried with little long-term success.⁴ Moisturizing may help reduce fissuring, and patients are advised to avoid the sun and repeated trauma to the hands.

The differential diagnosis of CEMPH is summarized in the Table. Two genodermatoses—acrokeratoelastoidosis of Costa and focal acral hyperkeratosis—clinically resemble CEMPH. Acrokeratoelastoidosis of Costa is an autosomal-dominant condition that occurs without trauma in children and young adults. Histopathology shows orthokeratotic hyperkeratosis due to an overproduction of filaggrin in the granular layer of the epidermis. The reticular dermis shows basophilic, thick, curled and fragmented elastic fibers with dilated capillaries that can be seen with Weigert elastic, Verhoeff-van Gieson, or orcein stains. Focal acral hyperkeratosis occurs on the hands and feet, predominantly in black patients. On histology, the epidermis shows a characteristic orthohyperkeratosis, moderate acanthosis, and slight hypergranulosis with no dermal involvment.⁶

CT099003025_e_Table.JPG

Chronic hyperkeratotic eczematous dermatitis is another common entity in the differential characterized by hyperkeratotic plaques that scale and fissure. Biopsy demonstrates a spongiotic acanthotic epidermis.^7,8

Psoriasis of the hands, specifically hyperkeratotic palmoplantar psoriasis, is associated with manual labor, similar to CEMPH. Histology shows epidermal hyperplasia; regular acanthosis; loss of the granular skin layer with prominent dermal capillaries; and a mixed dermal infiltrate of lymphocytes, macrophages, and neutrophils.⁹ Hyperkeratotic palmoplantar lichen planus presents with pruritic papules in the third and fifth decades of life. Histologically, hyperkeratosis, acanthosis, and wedge-shaped hypergranulosis with a lichenoid lymphocytic infiltration at the dermoepidermal junction is seen.¹⁰

Palmoplantar keratodermas due to inflammatory reactive dermatoses include callosities that develop in response to repeated trauma or friction on the skin. On histology, there is prominent hyperkeratosis and acanthosis with moderate papillomatosis.¹¹ Drug-related palmoplantar keratodermas such as those from arsenic exposure can lead to multiple, irregular, verrucous, keratotic, and pigmented lesions on the palms and soles. Histologically, atypical keratinocytes are seen in the epidermis with thick hyperkeratosis and vacuolated cells without solar elastosis.¹²

In conclusion, CEMPH is an underdiagnosed and underrecognized condition characterized by asymptomatic hyperkeratotic linear plaques along the medial aspect of the thumb and radial aspect of the index finger. It is important to keep CEMPH in mind when dealing with occupational cases of repeated long-term trauma or pressure to the hands as well as excessive sun exposure. It also is imperative to separate it from other diseases and avoid misdiagnosing this degenerative collagenous and elastotic disease as a malignant lesion. 

To the Editor:
Collagenous and elastotic marginal plaques of the hands (CEMPHs) has several names including degenerative collagenous plaques of the hands, keratoelastoidosis marginalis, and digital papular calcific elastosis. This rare disorder is an acquired, slowly progressive, asymptomatic, dermal connective tissue abnormality that is underrecognized and underdiagnosed. Clinical presentation includes hyperkeratotic translucent papules arranged linearly on the radial aspect of the hands.

A 74-year-old woman described having "rough hands" of more than 20 years' duration. She presented with 4-cm wide longitudinal, erythematous, firm, depressed plaques along the lateral edge of the second finger and extending to the medial thumb in both hands (Figure 1). She had attempted multiple treatments by her primary care physician, including topical and oral medications unknown to the patient and light therapy, all without benefit over a period of several years. We have attempted salicylic acid 40%, clobetasol cream 0.05%, and emollient creams containing α-hydroxy acid. At best the condition fluctuated between a subtle raised scale at the edge to smooth and occasionally more red-pink, seemingly unrelated to any treatments.

ct099003025_e_fig1.png

The patient did not have plaques elsewhere on the body, and notably, the feet were clear. She did not have a history of repeated trauma to the hands and did not engage in manual labor. She denied excessive sun exposure, though she had Fitzpatrick skin type III and a history of multiple precancers and nonmelanoma skin cancers 7 years prior to presentation.

Histology of CEMPH reveals a hyperkeratotic epidermis with an avascular and acellular replacement of the superficial reticular dermis by haphazardly arranged, thickened collagen fibers (Figure 2A-2C). Collagen fibers were oriented perpendicularly to the epidermal surface. Intervening amorphous basophilic elastotic masses were present in the upper dermis with occasional calcification and degenerative elastic fibers (Figure 2D).

ct099003025_e_fig.png

Collagenous and elastotic marginal plaques of the hands is a chronic, asymptomatic, sclerotic skin disorder described in a 1960 case series of 5 patients reported by Burks et al.¹ Although it has many names, the most common is CEMPH. Collagenous and elastotic marginal plaques of the hands most often presents in white men aged 50 to 60 years.² Patients typically are asymptomatic with plaques limited to the junction of the palmar and dorsal surfaces of the hands with only minimal intermittent stiffness around the flexor creases. Lesions begin as discrete yellow papules that coalesce to form hyperkeratotic linear plaques with occasional telangiectasia.³

The etiology of CEMPH is attributed to collagen and elastin degeneration by chronic actinic damage, pressure, or trauma.^4,5 The 3 stages of degeneration include an initial linear padded stage, an intermediate padded plaque stage, and an advanced padded hyperkeratotic plaque stage.⁴ Vascular compromise is seen from the enlarged and fused thickened collagen and elastic fibers that in turn lead to ischemic changes, hyperkeratosis with epidermal atrophy, and papillary dermis telangiectasia. Absence or weak expression of keratins 14 and 10 and strong expression of keratin 16 have been reported in the epidermis of CEMPH patients.⁴

Collagenous and elastotic marginal plaques of the hands do not have a specific treatment, as it is a benign, slowly progressive condition. Several treatments such as laser therapy, high-potency topical corticosteroids, topical tazarotene and tretinoin, oral isotretinoin, and cryotherapy have been tried with little long-term success.⁴ Moisturizing may help reduce fissuring, and patients are advised to avoid the sun and repeated trauma to the hands.

The differential diagnosis of CEMPH is summarized in the Table. Two genodermatoses—acrokeratoelastoidosis of Costa and focal acral hyperkeratosis—clinically resemble CEMPH. Acrokeratoelastoidosis of Costa is an autosomal-dominant condition that occurs without trauma in children and young adults. Histopathology shows orthokeratotic hyperkeratosis due to an overproduction of filaggrin in the granular layer of the epidermis. The reticular dermis shows basophilic, thick, curled and fragmented elastic fibers with dilated capillaries that can be seen with Weigert elastic, Verhoeff-van Gieson, or orcein stains. Focal acral hyperkeratosis occurs on the hands and feet, predominantly in black patients. On histology, the epidermis shows a characteristic orthohyperkeratosis, moderate acanthosis, and slight hypergranulosis with no dermal involvment.⁶

CT099003025_e_Table.JPG

Chronic hyperkeratotic eczematous dermatitis is another common entity in the differential characterized by hyperkeratotic plaques that scale and fissure. Biopsy demonstrates a spongiotic acanthotic epidermis.^7,8

Psoriasis of the hands, specifically hyperkeratotic palmoplantar psoriasis, is associated with manual labor, similar to CEMPH. Histology shows epidermal hyperplasia; regular acanthosis; loss of the granular skin layer with prominent dermal capillaries; and a mixed dermal infiltrate of lymphocytes, macrophages, and neutrophils.⁹ Hyperkeratotic palmoplantar lichen planus presents with pruritic papules in the third and fifth decades of life. Histologically, hyperkeratosis, acanthosis, and wedge-shaped hypergranulosis with a lichenoid lymphocytic infiltration at the dermoepidermal junction is seen.¹⁰

Palmoplantar keratodermas due to inflammatory reactive dermatoses include callosities that develop in response to repeated trauma or friction on the skin. On histology, there is prominent hyperkeratosis and acanthosis with moderate papillomatosis.¹¹ Drug-related palmoplantar keratodermas such as those from arsenic exposure can lead to multiple, irregular, verrucous, keratotic, and pigmented lesions on the palms and soles. Histologically, atypical keratinocytes are seen in the epidermis with thick hyperkeratosis and vacuolated cells without solar elastosis.¹²

In conclusion, CEMPH is an underdiagnosed and underrecognized condition characterized by asymptomatic hyperkeratotic linear plaques along the medial aspect of the thumb and radial aspect of the index finger. It is important to keep CEMPH in mind when dealing with occupational cases of repeated long-term trauma or pressure to the hands as well as excessive sun exposure. It also is imperative to separate it from other diseases and avoid misdiagnosing this degenerative collagenous and elastotic disease as a malignant lesion.