Tender Dermal Nodule on the Temple

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Tender Dermal Nodule on the Temple

The Diagnosis: Lymphoepithelioma-like Carcinoma

Lymphoepithelioma-like carcinoma (LELC) is a rare, poorly differentiated, primary cutaneous neoplasm that occurs on sun-exposed skin, particularly on the head and neck of elderly individuals. It often manifests as an asymptomatic, slow-growing, flesh-colored or erythematous dermal nodule, though ulceration and tenderness have been reported.1 Histopathologically, these neoplasms often are poorly circumscribed and can infiltrate surrounding subcutaneous and soft tissue. As a biphasic tumor, LELC is characterized by islands, nests, or trabeculae of epithelioid cells within the mid dermis surrounded by a dense lymphocytic infiltrate with plasma cells (Figure 1).1 The epithelial component rarely communicates with the overlying epidermis and is composed of atypical polygonal cells with eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, and frequent mitosis.2 These epithelial nests can be highlighted by pancytokeratin AE1/AE3 or other epithelial differentiation markers (eg, CAM 5.2, CK5/6, epithelial membrane antigen, high-molecular-weight cytokeratin), while the surrounding lymphocytic infiltrate consists of an admixture of T cells and B cells. Lymphoepithelioma-like carcinomas also can demonstrate sebaceous, eccrine, or follicular differentiations.3 The epithelial nests of LELC also are positive for p63 and epithelial membrane antigen.2

Chaiprasit_1.jpg
%3Cp%3E%3Cstrong%3EFIGURE%201.%3C%2Fstrong%3E%20Lymphoepithelial-like%20carcinoma.%20Dermal%20nests%20of%20epithelioid%20cells%20surrounded%20by%20a%20dense%20lymphocytic%20infiltrate%20are%20observed.%20The%20overlying%20epidermis%20is%20uninvolved%20(H%26amp%3BE%2C%20original%20magnification%20%C3%9740).%3C%2Fp%3E

The usual treatment of LELC is wide local excision or Mohs micrographic surgery.1 Despite the poorly differentiated morphology of the tumor, LELC has a generally good prognosis with low metastatic potential and few reports of local recurrence after incomplete excision.3 Patients who are not candidates for surgery as well as recalcitrant cases are managed with radiotherapy.1

Cutaneous lymphadenoma (CL) is a benign adnexal neoplasm that manifests as a small, solitary, fleshcolored nodule usually in the head and neck region.4 Histologically, CL consists of well-circumscribed epithelial nests within the dermis that are peripherally outlined by palisading basaloid cells and filled with clear to eosinophilic epithelioid cells (Figure 2).5 The fibrotic tumor stroma often is infiltrated by numerous intralobular dendritic cells and lymphocytes that occasionally can be arranged in germinal center–like nodules.4 The lymphoepithelial nature of CL can be challenging to distinguish morphologically from LELC, and immunohistochemistry stains may be required. In CL, both the basaloid and epithelioid cells stain positive for pancytokeratin AE1/ AE3, but the peripheral palisaded basaloid cells also stain positive for BerEP4. Additionally, the fibrotic stroma can be highlighted by CD34 and the intralobular dendritic cells by S-100.4

Chaiprasit_2.jpg
%3Cp%3E%3Cstrong%3EFIGURE%202.%3C%2Fstrong%3E%20Cutaneous%20lymphadenoma.%20Nests%20of%20clear%20epithelioid%20cells%20with%20peripheral%20basaloid%20cells%20are%20present%20within%20the%20dermis.%20The%20tumor%20stroma%20is%20fibrotic%20with%20lymphocytic%20infiltration%20(H%26amp%3BE%2C%20original%20magnification%20%C3%97100%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

Nasopharyngeal carcinoma (NPC), formerly known as lymphoepithelioma, refers to carcinoma arising within the epithelium of the nasopharynx.6 Endemic to China, NPC manifests as an enlarging nasopharyngeal mass, causing clinical symptoms such as nasal obstruction and epistaxis.7 Histologically, nonkeratinizing NPC exhibits a biphasic morphology consisting of epithelioid neoplastic cells and background lymphocytic infiltrates (Figure 3). The epithelial component consists of round to oval neoplastic cells with amphophilic to eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli.6 Nasopharyngeal carcinoma is associated strongly with the Epstein-Barr virus while LELC is not; thus, Epstein- Barr encoding region in situ hybridization can reliably distinguish these entities. Metastatic NPC is rare but has been reported; therefore, it is highly recommended to perform an otolaryngologic examination in addition to testing for Epstein-Barr virus reactivity as part of a complete evaluation.8

Chaiprasit_3.jpg
%3Cp%3E%3Cstrong%3EFIGURE%203.%3C%2Fstrong%3E%20Nonkeratinizing%20nasopharyngeal%20carcinoma%20(formerly%20known%20as%20lymphoepithelioma).%20A%20dense%20lymphocytic%20infiltrate%20is%20present%20in%20the%20background%20of%20basaloid%20epithelial%20nests%20(H%26amp%3BE%2C%20original%20magnification%20%C3%97100%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

Cutaneous squamous cell carcinoma (SCC) is a common epidermal malignancy with multiple subtypes and variable morphology. The clinical presentation of SCC is similar to LELC—an enlarging hyperkeratotic papule or nodule on sun-exposed skin that often is ulcerated and tender.9 Histologically, poorly differentiated nonkeratinizing SCC can form nests and trabeculae of epithelioid cells that are stained by epithelial differentiation markers, resembling the epithelioid nests of LELC. Distinguishing between LELC and poorly differentiated SCC with robust inflammatory infiltrate can be challenging (Figure 4). In fact, some experts support LELC as an SCC variant rather than a separate entity.9 However, in contrast to LELC, the dermal nests of SCC usually maintain an epidermal connection and often are associated with an overlying area of SCC in situ or welldifferentiated SCC.3

Chaiprasit_4.jpg
%3Cp%3E%3Cstrong%3EFIGURE%204.%3C%2Fstrong%3E%20Poorly%20differentiated%20squamous%20cell%20carcinoma.%20Robust%20inflammation%20is%20present%20as%20well%20as%20infiltrative%20nests%20and%20trabeculae%20of%20neoplastic%20epithelial%20cells%20with%20surrounding%20desmoplastic%20reaction%20and%20brisk%20mixed%20inflammatory%20infiltrate.%20The%20associated%20squamous%20cell%20carcinoma%20in%20situ%20also%20is%20present%20in%20the%20overlying%20epidermis%20(H%26amp%3BE%2C%20original%20magnification%20%C3%97100%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma. It is the most common type of cutaneous lymphoma, accounting for almost 50% of all reported cases.10 Classic MF has an indolent course and progresses through several clinical stages. Patches and plaques characterize early stages; lymphadenopathy indicates progression to later stages in which erythroderma may develop with coalescence of patches, plaques, and tumors; and MF present in blood or lymph nodes characterizes the late stage. Each stage of MF is different histologically—from a superficial lichenoid infiltrate with exocytosis of malignant T cells in the patch stage, to more robust epidermotropism and dermal infiltrate in the plaque stage, and finally a dense dermal infiltrate in the late stage.11 The rare syringotropic variant of MF clinically manifests as solitary or multiple erythematous lesions, often with overlying alopecia. Syringotropic MF uniquely exhibits folliculotropism and syringotropism along with syringometaplasia on histologic evaluation (Figure 5).12 The syringometaplasia can be difficult to distinguish from the epithelial nests of LELC, particularly with the lymphocytic background. Immunohistochemical panels for T-cell markers can highlight aberrant T cells in syringotropic MF through their usual loss of CD5 and CD7, in comparison to normal T cells in LELC.11 An elevated CD4:CD8 ratio of 4:1 and molecular analysis for T-cell receptor gene clonal rearrangements also can support the diagnosis of MF.12

Chaiprasit_5.jpg
%3Cp%3E%3Cstrong%3EFIGURE%205.%3C%2Fstrong%3E%20Syringotropic%20mycosis%20fungoides.%20A%20dermal%20infiltrate%20of%20neoplastic%20T%20cells%20exhibiting%20syringotropism%20can%20be%20observed.%20The%20involved%20eccrine%20glands%20shows%20focal%20areas%20of%20syringometaplasia%20(H%26amp%3BE%2C%20original%20magnification%20%C3%9740%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

References
  1. Morteza Abedi S, Salama S, Alowami S. Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out. Rare Tumors. 2013;5:E47.
  2. Fisher JC, White RM, Hurd DS. Lymphoepithelioma-like carcinoma of the skin: a case of one patient presenting with two primary cutaneous neoplasms. J Am Osteopath Coll Dermatol. 2015;33:40-41.
  3. Welch PQ, Williams SB, Foss RD, et al. Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:78-86.
  4. Yu R, Salama S, Alowami S. Cutaneous lymphadenoma: a rare case and brief review of a diagnostic pitfall. Rare Tumors. 2014;6:5358.
  5. Monteagudo C, Fúnez R, Sánchez-Sendra B, et al. Cutaneous lymphadenoma is a distinct trichoblastoma-like lymphoepithelial tumor with diffuse androgen receptor immunoreactivity, Notch1 ligand in Reed-Sternberg-like Cells, and common EGFR somatic mutations. Am J Surg Pathol. 2021;45:1382-1390.
  6. Stelow EB, Wenig BM. Update from the 4th edition of the World Health Organization classification of head and neck tumours: nasopharynx. Head Neck Pathol. 2017;11:16-22.
  7. Almomani MH, Zulfiqar H, Nagalli S. Nasopharyngeal carcinoma (NPC, lymphoepithelioma). StatPearls Publishing; 2022.
  8. Lassen CB, Lock-Andersen J. Lymphoepithelioma-like carcinoma of the skin: a case with perineural invasion. Plast Reconstr Surg Glob Open. 2014;2:E252.
  9. Motaparthi K, Kapil JP, Velazquez EF. Cutaneous squamous cell carcinoma: review of the eighth edition of the American Joint Committee on Cancer Staging Guidelines, Prognostic Factors, and Histopathologic Variants. Adv Anat Pathol. 2017;24:171-194.
  10. Pileri A, Facchetti F, Rütten A, et al. Syringotropic mycosis fungoides: a rare variant of the disease with peculiar clinicopathologic features. Am J Surg Pathol. 2011;35:100-109.
  11. Ryu HJ, Kim SI, Jang HO, et al. Evaluation of the International Society for Cutaneous Lymphoma Algorithm for the Diagnosis of Early Mycosis Fungoides [published October 15, 2021]. Cells. 2021;10:2758. doi:10.3390/cells10102758
  12. Lehmer LM, Amber KT, de Feraudy SM. Syringotropic mycosis fungoides: a rare form of cutaneous T-cell lymphoma enabling a histopathologic “sigh of relief.” Am J Dermatopathol. 2017;39:920-923.
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Drs. Chaiprasit, Modi, and Speiser are from the Department of Pathology, Loyola University Medical Center, Maywood, Illinois. Austin C. Casillas is from the Morehouse School of Medicine, Atlanta, Georgia.

The authors report no conflict of interest.

Correspondence: Thanchanok Chaiprasit, MD, Department of Pathology, Loyola University Medical Center, 2160 S First Ave, Building 110, Room 2232, Maywood, IL 60153 (thanchanok.chaiprasit@luhs.org).

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Author and Disclosure Information

Drs. Chaiprasit, Modi, and Speiser are from the Department of Pathology, Loyola University Medical Center, Maywood, Illinois. Austin C. Casillas is from the Morehouse School of Medicine, Atlanta, Georgia.

The authors report no conflict of interest.

Correspondence: Thanchanok Chaiprasit, MD, Department of Pathology, Loyola University Medical Center, 2160 S First Ave, Building 110, Room 2232, Maywood, IL 60153 (thanchanok.chaiprasit@luhs.org).

Author and Disclosure Information

Drs. Chaiprasit, Modi, and Speiser are from the Department of Pathology, Loyola University Medical Center, Maywood, Illinois. Austin C. Casillas is from the Morehouse School of Medicine, Atlanta, Georgia.

The authors report no conflict of interest.

Correspondence: Thanchanok Chaiprasit, MD, Department of Pathology, Loyola University Medical Center, 2160 S First Ave, Building 110, Room 2232, Maywood, IL 60153 (thanchanok.chaiprasit@luhs.org).

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The Diagnosis: Lymphoepithelioma-like Carcinoma

Lymphoepithelioma-like carcinoma (LELC) is a rare, poorly differentiated, primary cutaneous neoplasm that occurs on sun-exposed skin, particularly on the head and neck of elderly individuals. It often manifests as an asymptomatic, slow-growing, flesh-colored or erythematous dermal nodule, though ulceration and tenderness have been reported.1 Histopathologically, these neoplasms often are poorly circumscribed and can infiltrate surrounding subcutaneous and soft tissue. As a biphasic tumor, LELC is characterized by islands, nests, or trabeculae of epithelioid cells within the mid dermis surrounded by a dense lymphocytic infiltrate with plasma cells (Figure 1).1 The epithelial component rarely communicates with the overlying epidermis and is composed of atypical polygonal cells with eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, and frequent mitosis.2 These epithelial nests can be highlighted by pancytokeratin AE1/AE3 or other epithelial differentiation markers (eg, CAM 5.2, CK5/6, epithelial membrane antigen, high-molecular-weight cytokeratin), while the surrounding lymphocytic infiltrate consists of an admixture of T cells and B cells. Lymphoepithelioma-like carcinomas also can demonstrate sebaceous, eccrine, or follicular differentiations.3 The epithelial nests of LELC also are positive for p63 and epithelial membrane antigen.2

Chaiprasit_1.jpg
%3Cp%3E%3Cstrong%3EFIGURE%201.%3C%2Fstrong%3E%20Lymphoepithelial-like%20carcinoma.%20Dermal%20nests%20of%20epithelioid%20cells%20surrounded%20by%20a%20dense%20lymphocytic%20infiltrate%20are%20observed.%20The%20overlying%20epidermis%20is%20uninvolved%20(H%26amp%3BE%2C%20original%20magnification%20%C3%9740).%3C%2Fp%3E

The usual treatment of LELC is wide local excision or Mohs micrographic surgery.1 Despite the poorly differentiated morphology of the tumor, LELC has a generally good prognosis with low metastatic potential and few reports of local recurrence after incomplete excision.3 Patients who are not candidates for surgery as well as recalcitrant cases are managed with radiotherapy.1

Cutaneous lymphadenoma (CL) is a benign adnexal neoplasm that manifests as a small, solitary, fleshcolored nodule usually in the head and neck region.4 Histologically, CL consists of well-circumscribed epithelial nests within the dermis that are peripherally outlined by palisading basaloid cells and filled with clear to eosinophilic epithelioid cells (Figure 2).5 The fibrotic tumor stroma often is infiltrated by numerous intralobular dendritic cells and lymphocytes that occasionally can be arranged in germinal center–like nodules.4 The lymphoepithelial nature of CL can be challenging to distinguish morphologically from LELC, and immunohistochemistry stains may be required. In CL, both the basaloid and epithelioid cells stain positive for pancytokeratin AE1/ AE3, but the peripheral palisaded basaloid cells also stain positive for BerEP4. Additionally, the fibrotic stroma can be highlighted by CD34 and the intralobular dendritic cells by S-100.4

Chaiprasit_2.jpg
%3Cp%3E%3Cstrong%3EFIGURE%202.%3C%2Fstrong%3E%20Cutaneous%20lymphadenoma.%20Nests%20of%20clear%20epithelioid%20cells%20with%20peripheral%20basaloid%20cells%20are%20present%20within%20the%20dermis.%20The%20tumor%20stroma%20is%20fibrotic%20with%20lymphocytic%20infiltration%20(H%26amp%3BE%2C%20original%20magnification%20%C3%97100%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

Nasopharyngeal carcinoma (NPC), formerly known as lymphoepithelioma, refers to carcinoma arising within the epithelium of the nasopharynx.6 Endemic to China, NPC manifests as an enlarging nasopharyngeal mass, causing clinical symptoms such as nasal obstruction and epistaxis.7 Histologically, nonkeratinizing NPC exhibits a biphasic morphology consisting of epithelioid neoplastic cells and background lymphocytic infiltrates (Figure 3). The epithelial component consists of round to oval neoplastic cells with amphophilic to eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli.6 Nasopharyngeal carcinoma is associated strongly with the Epstein-Barr virus while LELC is not; thus, Epstein- Barr encoding region in situ hybridization can reliably distinguish these entities. Metastatic NPC is rare but has been reported; therefore, it is highly recommended to perform an otolaryngologic examination in addition to testing for Epstein-Barr virus reactivity as part of a complete evaluation.8

Chaiprasit_3.jpg
%3Cp%3E%3Cstrong%3EFIGURE%203.%3C%2Fstrong%3E%20Nonkeratinizing%20nasopharyngeal%20carcinoma%20(formerly%20known%20as%20lymphoepithelioma).%20A%20dense%20lymphocytic%20infiltrate%20is%20present%20in%20the%20background%20of%20basaloid%20epithelial%20nests%20(H%26amp%3BE%2C%20original%20magnification%20%C3%97100%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

Cutaneous squamous cell carcinoma (SCC) is a common epidermal malignancy with multiple subtypes and variable morphology. The clinical presentation of SCC is similar to LELC—an enlarging hyperkeratotic papule or nodule on sun-exposed skin that often is ulcerated and tender.9 Histologically, poorly differentiated nonkeratinizing SCC can form nests and trabeculae of epithelioid cells that are stained by epithelial differentiation markers, resembling the epithelioid nests of LELC. Distinguishing between LELC and poorly differentiated SCC with robust inflammatory infiltrate can be challenging (Figure 4). In fact, some experts support LELC as an SCC variant rather than a separate entity.9 However, in contrast to LELC, the dermal nests of SCC usually maintain an epidermal connection and often are associated with an overlying area of SCC in situ or welldifferentiated SCC.3

Chaiprasit_4.jpg
%3Cp%3E%3Cstrong%3EFIGURE%204.%3C%2Fstrong%3E%20Poorly%20differentiated%20squamous%20cell%20carcinoma.%20Robust%20inflammation%20is%20present%20as%20well%20as%20infiltrative%20nests%20and%20trabeculae%20of%20neoplastic%20epithelial%20cells%20with%20surrounding%20desmoplastic%20reaction%20and%20brisk%20mixed%20inflammatory%20infiltrate.%20The%20associated%20squamous%20cell%20carcinoma%20in%20situ%20also%20is%20present%20in%20the%20overlying%20epidermis%20(H%26amp%3BE%2C%20original%20magnification%20%C3%97100%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma. It is the most common type of cutaneous lymphoma, accounting for almost 50% of all reported cases.10 Classic MF has an indolent course and progresses through several clinical stages. Patches and plaques characterize early stages; lymphadenopathy indicates progression to later stages in which erythroderma may develop with coalescence of patches, plaques, and tumors; and MF present in blood or lymph nodes characterizes the late stage. Each stage of MF is different histologically—from a superficial lichenoid infiltrate with exocytosis of malignant T cells in the patch stage, to more robust epidermotropism and dermal infiltrate in the plaque stage, and finally a dense dermal infiltrate in the late stage.11 The rare syringotropic variant of MF clinically manifests as solitary or multiple erythematous lesions, often with overlying alopecia. Syringotropic MF uniquely exhibits folliculotropism and syringotropism along with syringometaplasia on histologic evaluation (Figure 5).12 The syringometaplasia can be difficult to distinguish from the epithelial nests of LELC, particularly with the lymphocytic background. Immunohistochemical panels for T-cell markers can highlight aberrant T cells in syringotropic MF through their usual loss of CD5 and CD7, in comparison to normal T cells in LELC.11 An elevated CD4:CD8 ratio of 4:1 and molecular analysis for T-cell receptor gene clonal rearrangements also can support the diagnosis of MF.12

Chaiprasit_5.jpg
%3Cp%3E%3Cstrong%3EFIGURE%205.%3C%2Fstrong%3E%20Syringotropic%20mycosis%20fungoides.%20A%20dermal%20infiltrate%20of%20neoplastic%20T%20cells%20exhibiting%20syringotropism%20can%20be%20observed.%20The%20involved%20eccrine%20glands%20shows%20focal%20areas%20of%20syringometaplasia%20(H%26amp%3BE%2C%20original%20magnification%20%C3%9740%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

The Diagnosis: Lymphoepithelioma-like Carcinoma

Lymphoepithelioma-like carcinoma (LELC) is a rare, poorly differentiated, primary cutaneous neoplasm that occurs on sun-exposed skin, particularly on the head and neck of elderly individuals. It often manifests as an asymptomatic, slow-growing, flesh-colored or erythematous dermal nodule, though ulceration and tenderness have been reported.1 Histopathologically, these neoplasms often are poorly circumscribed and can infiltrate surrounding subcutaneous and soft tissue. As a biphasic tumor, LELC is characterized by islands, nests, or trabeculae of epithelioid cells within the mid dermis surrounded by a dense lymphocytic infiltrate with plasma cells (Figure 1).1 The epithelial component rarely communicates with the overlying epidermis and is composed of atypical polygonal cells with eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, and frequent mitosis.2 These epithelial nests can be highlighted by pancytokeratin AE1/AE3 or other epithelial differentiation markers (eg, CAM 5.2, CK5/6, epithelial membrane antigen, high-molecular-weight cytokeratin), while the surrounding lymphocytic infiltrate consists of an admixture of T cells and B cells. Lymphoepithelioma-like carcinomas also can demonstrate sebaceous, eccrine, or follicular differentiations.3 The epithelial nests of LELC also are positive for p63 and epithelial membrane antigen.2

Chaiprasit_1.jpg
%3Cp%3E%3Cstrong%3EFIGURE%201.%3C%2Fstrong%3E%20Lymphoepithelial-like%20carcinoma.%20Dermal%20nests%20of%20epithelioid%20cells%20surrounded%20by%20a%20dense%20lymphocytic%20infiltrate%20are%20observed.%20The%20overlying%20epidermis%20is%20uninvolved%20(H%26amp%3BE%2C%20original%20magnification%20%C3%9740).%3C%2Fp%3E

The usual treatment of LELC is wide local excision or Mohs micrographic surgery.1 Despite the poorly differentiated morphology of the tumor, LELC has a generally good prognosis with low metastatic potential and few reports of local recurrence after incomplete excision.3 Patients who are not candidates for surgery as well as recalcitrant cases are managed with radiotherapy.1

Cutaneous lymphadenoma (CL) is a benign adnexal neoplasm that manifests as a small, solitary, fleshcolored nodule usually in the head and neck region.4 Histologically, CL consists of well-circumscribed epithelial nests within the dermis that are peripherally outlined by palisading basaloid cells and filled with clear to eosinophilic epithelioid cells (Figure 2).5 The fibrotic tumor stroma often is infiltrated by numerous intralobular dendritic cells and lymphocytes that occasionally can be arranged in germinal center–like nodules.4 The lymphoepithelial nature of CL can be challenging to distinguish morphologically from LELC, and immunohistochemistry stains may be required. In CL, both the basaloid and epithelioid cells stain positive for pancytokeratin AE1/ AE3, but the peripheral palisaded basaloid cells also stain positive for BerEP4. Additionally, the fibrotic stroma can be highlighted by CD34 and the intralobular dendritic cells by S-100.4

Chaiprasit_2.jpg
%3Cp%3E%3Cstrong%3EFIGURE%202.%3C%2Fstrong%3E%20Cutaneous%20lymphadenoma.%20Nests%20of%20clear%20epithelioid%20cells%20with%20peripheral%20basaloid%20cells%20are%20present%20within%20the%20dermis.%20The%20tumor%20stroma%20is%20fibrotic%20with%20lymphocytic%20infiltration%20(H%26amp%3BE%2C%20original%20magnification%20%C3%97100%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

Nasopharyngeal carcinoma (NPC), formerly known as lymphoepithelioma, refers to carcinoma arising within the epithelium of the nasopharynx.6 Endemic to China, NPC manifests as an enlarging nasopharyngeal mass, causing clinical symptoms such as nasal obstruction and epistaxis.7 Histologically, nonkeratinizing NPC exhibits a biphasic morphology consisting of epithelioid neoplastic cells and background lymphocytic infiltrates (Figure 3). The epithelial component consists of round to oval neoplastic cells with amphophilic to eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli.6 Nasopharyngeal carcinoma is associated strongly with the Epstein-Barr virus while LELC is not; thus, Epstein- Barr encoding region in situ hybridization can reliably distinguish these entities. Metastatic NPC is rare but has been reported; therefore, it is highly recommended to perform an otolaryngologic examination in addition to testing for Epstein-Barr virus reactivity as part of a complete evaluation.8

Chaiprasit_3.jpg
%3Cp%3E%3Cstrong%3EFIGURE%203.%3C%2Fstrong%3E%20Nonkeratinizing%20nasopharyngeal%20carcinoma%20(formerly%20known%20as%20lymphoepithelioma).%20A%20dense%20lymphocytic%20infiltrate%20is%20present%20in%20the%20background%20of%20basaloid%20epithelial%20nests%20(H%26amp%3BE%2C%20original%20magnification%20%C3%97100%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

Cutaneous squamous cell carcinoma (SCC) is a common epidermal malignancy with multiple subtypes and variable morphology. The clinical presentation of SCC is similar to LELC—an enlarging hyperkeratotic papule or nodule on sun-exposed skin that often is ulcerated and tender.9 Histologically, poorly differentiated nonkeratinizing SCC can form nests and trabeculae of epithelioid cells that are stained by epithelial differentiation markers, resembling the epithelioid nests of LELC. Distinguishing between LELC and poorly differentiated SCC with robust inflammatory infiltrate can be challenging (Figure 4). In fact, some experts support LELC as an SCC variant rather than a separate entity.9 However, in contrast to LELC, the dermal nests of SCC usually maintain an epidermal connection and often are associated with an overlying area of SCC in situ or welldifferentiated SCC.3

Chaiprasit_4.jpg
%3Cp%3E%3Cstrong%3EFIGURE%204.%3C%2Fstrong%3E%20Poorly%20differentiated%20squamous%20cell%20carcinoma.%20Robust%20inflammation%20is%20present%20as%20well%20as%20infiltrative%20nests%20and%20trabeculae%20of%20neoplastic%20epithelial%20cells%20with%20surrounding%20desmoplastic%20reaction%20and%20brisk%20mixed%20inflammatory%20infiltrate.%20The%20associated%20squamous%20cell%20carcinoma%20in%20situ%20also%20is%20present%20in%20the%20overlying%20epidermis%20(H%26amp%3BE%2C%20original%20magnification%20%C3%97100%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma. It is the most common type of cutaneous lymphoma, accounting for almost 50% of all reported cases.10 Classic MF has an indolent course and progresses through several clinical stages. Patches and plaques characterize early stages; lymphadenopathy indicates progression to later stages in which erythroderma may develop with coalescence of patches, plaques, and tumors; and MF present in blood or lymph nodes characterizes the late stage. Each stage of MF is different histologically—from a superficial lichenoid infiltrate with exocytosis of malignant T cells in the patch stage, to more robust epidermotropism and dermal infiltrate in the plaque stage, and finally a dense dermal infiltrate in the late stage.11 The rare syringotropic variant of MF clinically manifests as solitary or multiple erythematous lesions, often with overlying alopecia. Syringotropic MF uniquely exhibits folliculotropism and syringotropism along with syringometaplasia on histologic evaluation (Figure 5).12 The syringometaplasia can be difficult to distinguish from the epithelial nests of LELC, particularly with the lymphocytic background. Immunohistochemical panels for T-cell markers can highlight aberrant T cells in syringotropic MF through their usual loss of CD5 and CD7, in comparison to normal T cells in LELC.11 An elevated CD4:CD8 ratio of 4:1 and molecular analysis for T-cell receptor gene clonal rearrangements also can support the diagnosis of MF.12

Chaiprasit_5.jpg
%3Cp%3E%3Cstrong%3EFIGURE%205.%3C%2Fstrong%3E%20Syringotropic%20mycosis%20fungoides.%20A%20dermal%20infiltrate%20of%20neoplastic%20T%20cells%20exhibiting%20syringotropism%20can%20be%20observed.%20The%20involved%20eccrine%20glands%20shows%20focal%20areas%20of%20syringometaplasia%20(H%26amp%3BE%2C%20original%20magnification%20%C3%9740%3B%20inset%3A%20original%20magnification%20%C3%97400).%3C%2Fp%3E

References
  1. Morteza Abedi S, Salama S, Alowami S. Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out. Rare Tumors. 2013;5:E47.
  2. Fisher JC, White RM, Hurd DS. Lymphoepithelioma-like carcinoma of the skin: a case of one patient presenting with two primary cutaneous neoplasms. J Am Osteopath Coll Dermatol. 2015;33:40-41.
  3. Welch PQ, Williams SB, Foss RD, et al. Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:78-86.
  4. Yu R, Salama S, Alowami S. Cutaneous lymphadenoma: a rare case and brief review of a diagnostic pitfall. Rare Tumors. 2014;6:5358.
  5. Monteagudo C, Fúnez R, Sánchez-Sendra B, et al. Cutaneous lymphadenoma is a distinct trichoblastoma-like lymphoepithelial tumor with diffuse androgen receptor immunoreactivity, Notch1 ligand in Reed-Sternberg-like Cells, and common EGFR somatic mutations. Am J Surg Pathol. 2021;45:1382-1390.
  6. Stelow EB, Wenig BM. Update from the 4th edition of the World Health Organization classification of head and neck tumours: nasopharynx. Head Neck Pathol. 2017;11:16-22.
  7. Almomani MH, Zulfiqar H, Nagalli S. Nasopharyngeal carcinoma (NPC, lymphoepithelioma). StatPearls Publishing; 2022.
  8. Lassen CB, Lock-Andersen J. Lymphoepithelioma-like carcinoma of the skin: a case with perineural invasion. Plast Reconstr Surg Glob Open. 2014;2:E252.
  9. Motaparthi K, Kapil JP, Velazquez EF. Cutaneous squamous cell carcinoma: review of the eighth edition of the American Joint Committee on Cancer Staging Guidelines, Prognostic Factors, and Histopathologic Variants. Adv Anat Pathol. 2017;24:171-194.
  10. Pileri A, Facchetti F, Rütten A, et al. Syringotropic mycosis fungoides: a rare variant of the disease with peculiar clinicopathologic features. Am J Surg Pathol. 2011;35:100-109.
  11. Ryu HJ, Kim SI, Jang HO, et al. Evaluation of the International Society for Cutaneous Lymphoma Algorithm for the Diagnosis of Early Mycosis Fungoides [published October 15, 2021]. Cells. 2021;10:2758. doi:10.3390/cells10102758
  12. Lehmer LM, Amber KT, de Feraudy SM. Syringotropic mycosis fungoides: a rare form of cutaneous T-cell lymphoma enabling a histopathologic “sigh of relief.” Am J Dermatopathol. 2017;39:920-923.
References
  1. Morteza Abedi S, Salama S, Alowami S. Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out. Rare Tumors. 2013;5:E47.
  2. Fisher JC, White RM, Hurd DS. Lymphoepithelioma-like carcinoma of the skin: a case of one patient presenting with two primary cutaneous neoplasms. J Am Osteopath Coll Dermatol. 2015;33:40-41.
  3. Welch PQ, Williams SB, Foss RD, et al. Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:78-86.
  4. Yu R, Salama S, Alowami S. Cutaneous lymphadenoma: a rare case and brief review of a diagnostic pitfall. Rare Tumors. 2014;6:5358.
  5. Monteagudo C, Fúnez R, Sánchez-Sendra B, et al. Cutaneous lymphadenoma is a distinct trichoblastoma-like lymphoepithelial tumor with diffuse androgen receptor immunoreactivity, Notch1 ligand in Reed-Sternberg-like Cells, and common EGFR somatic mutations. Am J Surg Pathol. 2021;45:1382-1390.
  6. Stelow EB, Wenig BM. Update from the 4th edition of the World Health Organization classification of head and neck tumours: nasopharynx. Head Neck Pathol. 2017;11:16-22.
  7. Almomani MH, Zulfiqar H, Nagalli S. Nasopharyngeal carcinoma (NPC, lymphoepithelioma). StatPearls Publishing; 2022.
  8. Lassen CB, Lock-Andersen J. Lymphoepithelioma-like carcinoma of the skin: a case with perineural invasion. Plast Reconstr Surg Glob Open. 2014;2:E252.
  9. Motaparthi K, Kapil JP, Velazquez EF. Cutaneous squamous cell carcinoma: review of the eighth edition of the American Joint Committee on Cancer Staging Guidelines, Prognostic Factors, and Histopathologic Variants. Adv Anat Pathol. 2017;24:171-194.
  10. Pileri A, Facchetti F, Rütten A, et al. Syringotropic mycosis fungoides: a rare variant of the disease with peculiar clinicopathologic features. Am J Surg Pathol. 2011;35:100-109.
  11. Ryu HJ, Kim SI, Jang HO, et al. Evaluation of the International Society for Cutaneous Lymphoma Algorithm for the Diagnosis of Early Mycosis Fungoides [published October 15, 2021]. Cells. 2021;10:2758. doi:10.3390/cells10102758
  12. Lehmer LM, Amber KT, de Feraudy SM. Syringotropic mycosis fungoides: a rare form of cutaneous T-cell lymphoma enabling a histopathologic “sigh of relief.” Am J Dermatopathol. 2017;39:920-923.
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Cutis - 113(4)
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Tender Dermal Nodule on the Temple
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A 77-year-old man presented with a 1.2-cm dermal nodule on the left temple of 1 year’s duration. The lesion had become tender and darker in color. An excision was performed and submitted for histologic examination. Additional immunohistochemistry staining for Epstein-Barr virus was negative.

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