Joseph Dyer, DO

The Diagnosis: Majocchi Granuloma 

Majocchi granuloma (MG) is a dermatophytic infection that reveals hyphal elements within the cornified cells of follicles and most commonly is caused by Trichophyton rubrum. However, occasionally other Trichophyton, Trichosporon, and Aspergillus species are involved.¹  

There typically are 2 forms of MG: (1) the small perifollicular papular form that usually is localized to the dermis and occurs in immunocompetent individuals, and (2) a deep form featuring subcutaneous plaques and nodules that generally occur on the hair-bearing surfaces in immunosuppressed hosts.² Majocchi granuloma also commonly occurs from the use of potent topical steroids on unsuspected tinea.³  

Histopathologically, MG generally presents as granulomatous inflammation with perifollicular neutrophilic infiltration. This polymorphonuclear cell infiltrate was visible clinically as a single pustule overlying the nodular plaque, a clue appreciable only on close inspection. Histopathologic examination revealed segmented branching filaments present within cornified elements of a follicle (Figure). Notably, potassium hydroxide (KOH) preparations are unreliable diagnostic aids in MG, as evidenced by the 2 negative KOH preparations in this case. According to Chou and Hsu,⁴ because KOH preparation can only detect fungi located in the stratum corneum, the result may be negative for MG due to deeper invasion of the fungi into the dermal follicular component. In fact, KOH preparations of MG may reveal no hyphae in 23.3% of cases.²  

The initiating factor in MG is not entirely known but is thought to be physical trauma that either directly or indirectly leads to follicle disruption and passive introduction of the organism into the dermis (eg, traumatic implantation via gardening or other recreational activities).² Other proposed mechanisms include the presentation of the membrane-associated ATP-binding cassette transporter on the surface of T rubrum.¹ Dermatophytes evade the host immune system through a variety of mechanisms: (1) cell wall glycoproteins, (2) release of anti-inflammatory cytokines, and (3) generation of immunosuppressive regulatory T cells.¹ 

Collectively, the clinical and histopathologic findings distinguish MG from other cutaneous conditions. Sporotrichosis, a granulomatous infection caused by Sporothrix schenckii, typically is found in tropical regions of the world and often is associated with floriculture.⁵ Sporotrichosis initially presents in a subcutaneous papulonodular form, but unlike MG, it later ulcerates and progresses along adjacent lymphatic chains.⁵ Pathology of sporotrichosis exhibits pseudoepitheliomatous hyperplasia with granulomas, possible foci of suppuration, and yeastlike forms called cigar bodies. Chromoblastomycosis clinically is defined by tumorlike lesions on the skin including verrucous, nodular, or scarlike plaques and typically is associated with traumatic injury and implantation of the microorganism. Histologically, chromoblastomycosis demonstrates pseudoepitheliomatous hyperplasia with granulomas and characteristic darkly pigmented, thick-walled sclerotic cells called Medlar bodies.⁶Mycobacterium marinum is one cause of nontuberculous mycobacterial skin infections in humans. Clinically, M marinum is associated with improper hygiene techniques and contact with fish tanks and other aqueous environments. Mycobacterium marinum can present histopathologically as early neutrophilic infiltration or late dermal granulomatous inflammation.⁷ Acid-fast bacilli typically are scant, leaving the diagnosis best secured via polymerase chain reaction assay. Nodular Kaposi sarcoma (KS) can present as a dusky nodular plaque on an acral surface but typically is seen in patients with underlying human immunodeficiency virus/AIDS or other immunosuppressive conditions. The pathology for KS shows a proliferation of human herpes virus 8-positive spindle cells with slitlike spaces containing red blood cells instead of granulomatous inflammation. 

Treatment regimens with topical corticosteroids can exacerbate the infection due to local suppression of cell-mediated immunity.⁸ In these scenarios, fungal infection is suspected, and systemic antifungals such as ketoconazole; itraconazole; or terbinafine, which has become the mainstay, are prescribed. Resolution of the infection with these medications usually is seen after 4 weeks.² 

A diagnosis of MG can be elusive and often may take multiple visits. Clinicians should note that MG could demonstrate repeated false-negative KOH preparations; therefore, these tests should not be relied on as the sole determination of a diagnosis. Although chromoblastomycosis, sporotrichosis, nodular KS, and infection with M marinum may all present as nodular plaques with granulomatous pathology, a follicular pustule may be a clinical clue to MG, as its mimics typically lack folliculocentric neutrophils.

The Diagnosis: Majocchi Granuloma 

Majocchi granuloma (MG) is a dermatophytic infection that reveals hyphal elements within the cornified cells of follicles and most commonly is caused by Trichophyton rubrum. However, occasionally other Trichophyton, Trichosporon, and Aspergillus species are involved.¹  

There typically are 2 forms of MG: (1) the small perifollicular papular form that usually is localized to the dermis and occurs in immunocompetent individuals, and (2) a deep form featuring subcutaneous plaques and nodules that generally occur on the hair-bearing surfaces in immunosuppressed hosts.² Majocchi granuloma also commonly occurs from the use of potent topical steroids on unsuspected tinea.³  

Histopathologically, MG generally presents as granulomatous inflammation with perifollicular neutrophilic infiltration. This polymorphonuclear cell infiltrate was visible clinically as a single pustule overlying the nodular plaque, a clue appreciable only on close inspection. Histopathologic examination revealed segmented branching filaments present within cornified elements of a follicle (Figure). Notably, potassium hydroxide (KOH) preparations are unreliable diagnostic aids in MG, as evidenced by the 2 negative KOH preparations in this case. According to Chou and Hsu,⁴ because KOH preparation can only detect fungi located in the stratum corneum, the result may be negative for MG due to deeper invasion of the fungi into the dermal follicular component. In fact, KOH preparations of MG may reveal no hyphae in 23.3% of cases.²  

The initiating factor in MG is not entirely known but is thought to be physical trauma that either directly or indirectly leads to follicle disruption and passive introduction of the organism into the dermis (eg, traumatic implantation via gardening or other recreational activities).² Other proposed mechanisms include the presentation of the membrane-associated ATP-binding cassette transporter on the surface of T rubrum.¹ Dermatophytes evade the host immune system through a variety of mechanisms: (1) cell wall glycoproteins, (2) release of anti-inflammatory cytokines, and (3) generation of immunosuppressive regulatory T cells.¹ 

Collectively, the clinical and histopathologic findings distinguish MG from other cutaneous conditions. Sporotrichosis, a granulomatous infection caused by Sporothrix schenckii, typically is found in tropical regions of the world and often is associated with floriculture.⁵ Sporotrichosis initially presents in a subcutaneous papulonodular form, but unlike MG, it later ulcerates and progresses along adjacent lymphatic chains.⁵ Pathology of sporotrichosis exhibits pseudoepitheliomatous hyperplasia with granulomas, possible foci of suppuration, and yeastlike forms called cigar bodies. Chromoblastomycosis clinically is defined by tumorlike lesions on the skin including verrucous, nodular, or scarlike plaques and typically is associated with traumatic injury and implantation of the microorganism. Histologically, chromoblastomycosis demonstrates pseudoepitheliomatous hyperplasia with granulomas and characteristic darkly pigmented, thick-walled sclerotic cells called Medlar bodies.⁶Mycobacterium marinum is one cause of nontuberculous mycobacterial skin infections in humans. Clinically, M marinum is associated with improper hygiene techniques and contact with fish tanks and other aqueous environments. Mycobacterium marinum can present histopathologically as early neutrophilic infiltration or late dermal granulomatous inflammation.⁷ Acid-fast bacilli typically are scant, leaving the diagnosis best secured via polymerase chain reaction assay. Nodular Kaposi sarcoma (KS) can present as a dusky nodular plaque on an acral surface but typically is seen in patients with underlying human immunodeficiency virus/AIDS or other immunosuppressive conditions. The pathology for KS shows a proliferation of human herpes virus 8-positive spindle cells with slitlike spaces containing red blood cells instead of granulomatous inflammation. 

Treatment regimens with topical corticosteroids can exacerbate the infection due to local suppression of cell-mediated immunity.⁸ In these scenarios, fungal infection is suspected, and systemic antifungals such as ketoconazole; itraconazole; or terbinafine, which has become the mainstay, are prescribed. Resolution of the infection with these medications usually is seen after 4 weeks.² 

A diagnosis of MG can be elusive and often may take multiple visits. Clinicians should note that MG could demonstrate repeated false-negative KOH preparations; therefore, these tests should not be relied on as the sole determination of a diagnosis. Although chromoblastomycosis, sporotrichosis, nodular KS, and infection with M marinum may all present as nodular plaques with granulomatous pathology, a follicular pustule may be a clinical clue to MG, as its mimics typically lack folliculocentric neutrophils.

The Diagnosis: Majocchi Granuloma 

Majocchi granuloma (MG) is a dermatophytic infection that reveals hyphal elements within the cornified cells of follicles and most commonly is caused by Trichophyton rubrum. However, occasionally other Trichophyton, Trichosporon, and Aspergillus species are involved.¹  

There typically are 2 forms of MG: (1) the small perifollicular papular form that usually is localized to the dermis and occurs in immunocompetent individuals, and (2) a deep form featuring subcutaneous plaques and nodules that generally occur on the hair-bearing surfaces in immunosuppressed hosts.² Majocchi granuloma also commonly occurs from the use of potent topical steroids on unsuspected tinea.³  

Histopathologically, MG generally presents as granulomatous inflammation with perifollicular neutrophilic infiltration. This polymorphonuclear cell infiltrate was visible clinically as a single pustule overlying the nodular plaque, a clue appreciable only on close inspection. Histopathologic examination revealed segmented branching filaments present within cornified elements of a follicle (Figure). Notably, potassium hydroxide (KOH) preparations are unreliable diagnostic aids in MG, as evidenced by the 2 negative KOH preparations in this case. According to Chou and Hsu,⁴ because KOH preparation can only detect fungi located in the stratum corneum, the result may be negative for MG due to deeper invasion of the fungi into the dermal follicular component. In fact, KOH preparations of MG may reveal no hyphae in 23.3% of cases.²  

The initiating factor in MG is not entirely known but is thought to be physical trauma that either directly or indirectly leads to follicle disruption and passive introduction of the organism into the dermis (eg, traumatic implantation via gardening or other recreational activities).² Other proposed mechanisms include the presentation of the membrane-associated ATP-binding cassette transporter on the surface of T rubrum.¹ Dermatophytes evade the host immune system through a variety of mechanisms: (1) cell wall glycoproteins, (2) release of anti-inflammatory cytokines, and (3) generation of immunosuppressive regulatory T cells.¹ 

Collectively, the clinical and histopathologic findings distinguish MG from other cutaneous conditions. Sporotrichosis, a granulomatous infection caused by Sporothrix schenckii, typically is found in tropical regions of the world and often is associated with floriculture.⁵ Sporotrichosis initially presents in a subcutaneous papulonodular form, but unlike MG, it later ulcerates and progresses along adjacent lymphatic chains.⁵ Pathology of sporotrichosis exhibits pseudoepitheliomatous hyperplasia with granulomas, possible foci of suppuration, and yeastlike forms called cigar bodies. Chromoblastomycosis clinically is defined by tumorlike lesions on the skin including verrucous, nodular, or scarlike plaques and typically is associated with traumatic injury and implantation of the microorganism. Histologically, chromoblastomycosis demonstrates pseudoepitheliomatous hyperplasia with granulomas and characteristic darkly pigmented, thick-walled sclerotic cells called Medlar bodies.⁶Mycobacterium marinum is one cause of nontuberculous mycobacterial skin infections in humans. Clinically, M marinum is associated with improper hygiene techniques and contact with fish tanks and other aqueous environments. Mycobacterium marinum can present histopathologically as early neutrophilic infiltration or late dermal granulomatous inflammation.⁷ Acid-fast bacilli typically are scant, leaving the diagnosis best secured via polymerase chain reaction assay. Nodular Kaposi sarcoma (KS) can present as a dusky nodular plaque on an acral surface but typically is seen in patients with underlying human immunodeficiency virus/AIDS or other immunosuppressive conditions. The pathology for KS shows a proliferation of human herpes virus 8-positive spindle cells with slitlike spaces containing red blood cells instead of granulomatous inflammation. 

Treatment regimens with topical corticosteroids can exacerbate the infection due to local suppression of cell-mediated immunity.⁸ In these scenarios, fungal infection is suspected, and systemic antifungals such as ketoconazole; itraconazole; or terbinafine, which has become the mainstay, are prescribed. Resolution of the infection with these medications usually is seen after 4 weeks.² 

A diagnosis of MG can be elusive and often may take multiple visits. Clinicians should note that MG could demonstrate repeated false-negative KOH preparations; therefore, these tests should not be relied on as the sole determination of a diagnosis. Although chromoblastomycosis, sporotrichosis, nodular KS, and infection with M marinum may all present as nodular plaques with granulomatous pathology, a follicular pustule may be a clinical clue to MG, as its mimics typically lack folliculocentric neutrophils.

Case Report

A 78-year-old man presented for evaluation of 4 painful keratotic nodules that had appeared on the dorsal aspect of the right thumb, the first web space of the right hand, and the first web space of the left hand. The nodules developed in pericicatricial skin following Mohs micrographic surgery to the affected areas for treatment of invasive squamous cell carcinomas (SCCs) 2 months prior. The patient had worked in lawn maintenance for decades and continued to garden on an avocational basis. He denied exposure to angling or aquariums.

On physical examination the lesions appeared as firm, dusky-violaceous, crusted nodules (Figure 1). Brown patches of hyperpigmentation or characteristic cornlike elevations of the palm were not present to implicate arsenic exposure. Extensive sun damage to the face, neck, forearms, and dorsal aspect of the hands was noted. Epitrochlear lymphadenopathy or lymphangitic streaking were not appreciated. Routine hematologic parameters including leukocyte count were normal, except for chronic thrombocytopenia. Computerized tomography of the abdomen demonstrated no hepatosplenomegaly or enlarged lymph nodes. Hematoxylin and eosin staining of biopsy specimens from the right thumb showed irregular squamous epithelial hyperplasia with an impetiginized scale crust and pustular tissue reaction, including suppurative abscess formation in the dermis (Figure 2). Initial acid-fast staining performed on the biopsy from the right thumb was negative for microorganisms. Given the concerning histologic features indicating infection, a tissue culture was performed. Subsequent growth on Lowenstein-Jensen culture medium confirmed infection with Mycobacterium avium complex (MAC). The patient was started on clarithromycin 500 mg twice daily in accordance with laboratory susceptibilities, and the cutaneous nodules improved. Unfortunately, the patient died 6 months later secondary to cardiac arrest.

Comment

The genus Mycobacterium comprises more than 130 described bacteria, including the precipitants of tuberculosis and leprosy. Mycobacterium avium complex--an umbrella term for M avium, Mycobacterium intracellulare, and other close relatives--is a member of the genus that maintains a low pathogenicity for healthy individuals.^1,2 Nonetheless, MAC accounts for more than 70% of cases of nontuberculous mycobacterial disease in the United States.³Mycobacterium avium complex typically acts as a respiratory pathogen, but infection may manifest with lymphadenitis, osteomyelitis, hepatosplenomegaly, or skin involvement. Disseminated MAC infection can occur in patients with defective immune systems, including those with conditions such as AIDS or hairy cell leukemia and those undergoing immunosuppressive therapy.^1,4 Although uncommon, cutaneous infection with MAC occurs via 3 possible mechanisms: (1) primary inoculation, (2) lymphogenous extension, or (3) hematologic dissemination.⁴ According to a PubMed search of articles indexed for MEDLINE using the terms primary cutaneous Mycobacterium avium complex and MAC skin infection, only 11 known cases of primary cutaneous MAC infection have been reported in the English-language literature,^4-14  the most recent being a report by Landriscina et al.¹¹

A Runyon group III bacillus, MAC is a slow-growing nonchromogen that is ubiquitous in nature.¹⁵ It has been isolated from soil, water, house dust, vegetables, eggs, and milk. According to Reed et al,³ occupational exposure to soil is an independent risk factor for MAC infection, with individuals reporting more than 6 years of cumulative participation in lawn and landscaping services, farming, or other occupations involving substantial exposure to dirt or dust most likely to be MAC-positive. Cutaneous MAC infection may be associated with water exposure, as Sugita et al² described one familial outbreak of cutaneous MAC infection linked to use of a circulating, constantly heated bathwater system. With respect to US geography, individuals living in rural areas of the South seem most prone to MAC infection.³

Primary cutaneous infection with MAC occurs after a breach in the skin surface, though this fact may not be elicited by history. Modes of entry include minor abrasions after falling,¹ small wounds,² traumatic inoculation,¹⁵ and intramuscular injection.¹⁶ Clinically, cutaneous lesions of MAC are protean. In the literature, clinical presentation is described as a polymorphous appearance with scaling plaques, verrucous nodules, crusted ulcers, inflammatory nodules, dermatitis, panniculitis, draining sinuses, ecthymatous lesions, sporotrichoid growth patterns, or rosacealike papulopustules.^1,15,17 Lesions may affect the arms and legs, trunk, buttocks, and face.¹⁸

The differential diagnosis of MAC infection includes lupus vulgaris, Mycobacterium marinum infection (also known as swimming pool granuloma), sporotrichosis, nocardiosis, sarcoidosis, neutrophilic dermatosis, pyoderma gangrenosum, and cutaneous blastomycosis. Given its rarity and variability, diagnosis of MAC infection requires a high index of suspicion. Cutaneous MAC infection should be considered if a nodule, plaque, or ulcer fails to respond to conventional treatment, especially in patients with a history of environmental exposure and possible injury to the skin.

We report a rare case of primary cutaneous MAC infection arising in SCC excision sites in a patient without known immune deficiency. This presentation may have occurred for several reasons. First, the surgical excision sites coupled with the substantial occupational and recreational exposure to soil experienced by our patient may have served as portals for infection. Although SCCs are common on the hands, Mohs micrographic surgery is not always performed for excision; in our patient's case, this approach allowed for maximum tissue conservation and preserved manual function given the number and location of the lesions. Second, despite an overtly intact immune system, our patient may have harbored an occult immune deficiency, predisposing him to dermatologic infection with a microorganism of low intrinsic virulence and recurrent malignant neoplasms. This presentation may have been the first clinical indication of subtle immune compromise. For example, inadequate proinflammatory cytokines may contribute to both mycobacterial and malignant disease. A potential risk of inhibition of tumor necrosis factor α is the unmasking of tuberculosis or lymphoma.^19,20 Likewise, IFN-γ is vital in suppressing mycobacteria and malignancy. Yonekura et al²¹ found that IFN-γ induces apoptosis in oral SCC lines. It follows that a paucity of IFN-γ could allow neoplastic growth. Normal function of IFN-γ prompts microbicidal activity in macrophages and stimulates granuloma formation, both of which combat mycobacterial infection.¹⁹ A final postulation is that a simmering cutaneous MAC infection precipitated neoplastic degeneration into SCC, much the same way that the human papillomavirus has been correlated in the carcinogenesis of cervical cancer. As an intracellular microbe, MAC could cause the genetic machinery of skin cells to go awry. Kullavanijaya et al¹⁸ described a patient with cutaneous MAC in association with cervical cancer.

Conclusion

This association of primary cutaneous MAC infection and cutaneous malignancy in a reportedly immunocompetent patient is rare. Cancer patients, as noted by Feld et al,²² are 3 times more likely to develop infections with mycobacteria, with SCC, lymphoma, and leukemia being most commonly indicated. A specific immune deficit in the IFN-γ receptor is known to confer a selective predisposition to mycobacterial infection.^23,24 Toyoda et al²⁵ outlined the case of a pediatric patient with IFN-γ receptor 2 deficiency who presented with disseminated MAC infection and later succumbed to multiple SCCs of the hands and face. The authors' assertion was that inherited disorders of IFN-γ-mediated immunity may be associated with SCCs.²⁵ Unfortunately, our patient died before more specific immunological testing could be conducted. This case highlights the remarkable singularity of primary cutaneous MAC infection in association with multiple SCCs with seemingly intact immune status and offers some intriguing hypotheses regarding its occurrence.

Case Report

A 78-year-old man presented for evaluation of 4 painful keratotic nodules that had appeared on the dorsal aspect of the right thumb, the first web space of the right hand, and the first web space of the left hand. The nodules developed in pericicatricial skin following Mohs micrographic surgery to the affected areas for treatment of invasive squamous cell carcinomas (SCCs) 2 months prior. The patient had worked in lawn maintenance for decades and continued to garden on an avocational basis. He denied exposure to angling or aquariums.

On physical examination the lesions appeared as firm, dusky-violaceous, crusted nodules (Figure 1). Brown patches of hyperpigmentation or characteristic cornlike elevations of the palm were not present to implicate arsenic exposure. Extensive sun damage to the face, neck, forearms, and dorsal aspect of the hands was noted. Epitrochlear lymphadenopathy or lymphangitic streaking were not appreciated. Routine hematologic parameters including leukocyte count were normal, except for chronic thrombocytopenia. Computerized tomography of the abdomen demonstrated no hepatosplenomegaly or enlarged lymph nodes. Hematoxylin and eosin staining of biopsy specimens from the right thumb showed irregular squamous epithelial hyperplasia with an impetiginized scale crust and pustular tissue reaction, including suppurative abscess formation in the dermis (Figure 2). Initial acid-fast staining performed on the biopsy from the right thumb was negative for microorganisms. Given the concerning histologic features indicating infection, a tissue culture was performed. Subsequent growth on Lowenstein-Jensen culture medium confirmed infection with Mycobacterium avium complex (MAC). The patient was started on clarithromycin 500 mg twice daily in accordance with laboratory susceptibilities, and the cutaneous nodules improved. Unfortunately, the patient died 6 months later secondary to cardiac arrest.

Comment

The genus Mycobacterium comprises more than 130 described bacteria, including the precipitants of tuberculosis and leprosy. Mycobacterium avium complex--an umbrella term for M avium, Mycobacterium intracellulare, and other close relatives--is a member of the genus that maintains a low pathogenicity for healthy individuals.^1,2 Nonetheless, MAC accounts for more than 70% of cases of nontuberculous mycobacterial disease in the United States.³Mycobacterium avium complex typically acts as a respiratory pathogen, but infection may manifest with lymphadenitis, osteomyelitis, hepatosplenomegaly, or skin involvement. Disseminated MAC infection can occur in patients with defective immune systems, including those with conditions such as AIDS or hairy cell leukemia and those undergoing immunosuppressive therapy.^1,4 Although uncommon, cutaneous infection with MAC occurs via 3 possible mechanisms: (1) primary inoculation, (2) lymphogenous extension, or (3) hematologic dissemination.⁴ According to a PubMed search of articles indexed for MEDLINE using the terms primary cutaneous Mycobacterium avium complex and MAC skin infection, only 11 known cases of primary cutaneous MAC infection have been reported in the English-language literature,^4-14  the most recent being a report by Landriscina et al.¹¹

A Runyon group III bacillus, MAC is a slow-growing nonchromogen that is ubiquitous in nature.¹⁵ It has been isolated from soil, water, house dust, vegetables, eggs, and milk. According to Reed et al,³ occupational exposure to soil is an independent risk factor for MAC infection, with individuals reporting more than 6 years of cumulative participation in lawn and landscaping services, farming, or other occupations involving substantial exposure to dirt or dust most likely to be MAC-positive. Cutaneous MAC infection may be associated with water exposure, as Sugita et al² described one familial outbreak of cutaneous MAC infection linked to use of a circulating, constantly heated bathwater system. With respect to US geography, individuals living in rural areas of the South seem most prone to MAC infection.³

Primary cutaneous infection with MAC occurs after a breach in the skin surface, though this fact may not be elicited by history. Modes of entry include minor abrasions after falling,¹ small wounds,² traumatic inoculation,¹⁵ and intramuscular injection.¹⁶ Clinically, cutaneous lesions of MAC are protean. In the literature, clinical presentation is described as a polymorphous appearance with scaling plaques, verrucous nodules, crusted ulcers, inflammatory nodules, dermatitis, panniculitis, draining sinuses, ecthymatous lesions, sporotrichoid growth patterns, or rosacealike papulopustules.^1,15,17 Lesions may affect the arms and legs, trunk, buttocks, and face.¹⁸

The differential diagnosis of MAC infection includes lupus vulgaris, Mycobacterium marinum infection (also known as swimming pool granuloma), sporotrichosis, nocardiosis, sarcoidosis, neutrophilic dermatosis, pyoderma gangrenosum, and cutaneous blastomycosis. Given its rarity and variability, diagnosis of MAC infection requires a high index of suspicion. Cutaneous MAC infection should be considered if a nodule, plaque, or ulcer fails to respond to conventional treatment, especially in patients with a history of environmental exposure and possible injury to the skin.

We report a rare case of primary cutaneous MAC infection arising in SCC excision sites in a patient without known immune deficiency. This presentation may have occurred for several reasons. First, the surgical excision sites coupled with the substantial occupational and recreational exposure to soil experienced by our patient may have served as portals for infection. Although SCCs are common on the hands, Mohs micrographic surgery is not always performed for excision; in our patient's case, this approach allowed for maximum tissue conservation and preserved manual function given the number and location of the lesions. Second, despite an overtly intact immune system, our patient may have harbored an occult immune deficiency, predisposing him to dermatologic infection with a microorganism of low intrinsic virulence and recurrent malignant neoplasms. This presentation may have been the first clinical indication of subtle immune compromise. For example, inadequate proinflammatory cytokines may contribute to both mycobacterial and malignant disease. A potential risk of inhibition of tumor necrosis factor α is the unmasking of tuberculosis or lymphoma.^19,20 Likewise, IFN-γ is vital in suppressing mycobacteria and malignancy. Yonekura et al²¹ found that IFN-γ induces apoptosis in oral SCC lines. It follows that a paucity of IFN-γ could allow neoplastic growth. Normal function of IFN-γ prompts microbicidal activity in macrophages and stimulates granuloma formation, both of which combat mycobacterial infection.¹⁹ A final postulation is that a simmering cutaneous MAC infection precipitated neoplastic degeneration into SCC, much the same way that the human papillomavirus has been correlated in the carcinogenesis of cervical cancer. As an intracellular microbe, MAC could cause the genetic machinery of skin cells to go awry. Kullavanijaya et al¹⁸ described a patient with cutaneous MAC in association with cervical cancer.

Conclusion

This association of primary cutaneous MAC infection and cutaneous malignancy in a reportedly immunocompetent patient is rare. Cancer patients, as noted by Feld et al,²² are 3 times more likely to develop infections with mycobacteria, with SCC, lymphoma, and leukemia being most commonly indicated. A specific immune deficit in the IFN-γ receptor is known to confer a selective predisposition to mycobacterial infection.^23,24 Toyoda et al²⁵ outlined the case of a pediatric patient with IFN-γ receptor 2 deficiency who presented with disseminated MAC infection and later succumbed to multiple SCCs of the hands and face. The authors' assertion was that inherited disorders of IFN-γ-mediated immunity may be associated with SCCs.²⁵ Unfortunately, our patient died before more specific immunological testing could be conducted. This case highlights the remarkable singularity of primary cutaneous MAC infection in association with multiple SCCs with seemingly intact immune status and offers some intriguing hypotheses regarding its occurrence.

Case Report

A 78-year-old man presented for evaluation of 4 painful keratotic nodules that had appeared on the dorsal aspect of the right thumb, the first web space of the right hand, and the first web space of the left hand. The nodules developed in pericicatricial skin following Mohs micrographic surgery to the affected areas for treatment of invasive squamous cell carcinomas (SCCs) 2 months prior. The patient had worked in lawn maintenance for decades and continued to garden on an avocational basis. He denied exposure to angling or aquariums.

On physical examination the lesions appeared as firm, dusky-violaceous, crusted nodules (Figure 1). Brown patches of hyperpigmentation or characteristic cornlike elevations of the palm were not present to implicate arsenic exposure. Extensive sun damage to the face, neck, forearms, and dorsal aspect of the hands was noted. Epitrochlear lymphadenopathy or lymphangitic streaking were not appreciated. Routine hematologic parameters including leukocyte count were normal, except for chronic thrombocytopenia. Computerized tomography of the abdomen demonstrated no hepatosplenomegaly or enlarged lymph nodes. Hematoxylin and eosin staining of biopsy specimens from the right thumb showed irregular squamous epithelial hyperplasia with an impetiginized scale crust and pustular tissue reaction, including suppurative abscess formation in the dermis (Figure 2). Initial acid-fast staining performed on the biopsy from the right thumb was negative for microorganisms. Given the concerning histologic features indicating infection, a tissue culture was performed. Subsequent growth on Lowenstein-Jensen culture medium confirmed infection with Mycobacterium avium complex (MAC). The patient was started on clarithromycin 500 mg twice daily in accordance with laboratory susceptibilities, and the cutaneous nodules improved. Unfortunately, the patient died 6 months later secondary to cardiac arrest.

Comment

The genus Mycobacterium comprises more than 130 described bacteria, including the precipitants of tuberculosis and leprosy. Mycobacterium avium complex--an umbrella term for M avium, Mycobacterium intracellulare, and other close relatives--is a member of the genus that maintains a low pathogenicity for healthy individuals.^1,2 Nonetheless, MAC accounts for more than 70% of cases of nontuberculous mycobacterial disease in the United States.³Mycobacterium avium complex typically acts as a respiratory pathogen, but infection may manifest with lymphadenitis, osteomyelitis, hepatosplenomegaly, or skin involvement. Disseminated MAC infection can occur in patients with defective immune systems, including those with conditions such as AIDS or hairy cell leukemia and those undergoing immunosuppressive therapy.^1,4 Although uncommon, cutaneous infection with MAC occurs via 3 possible mechanisms: (1) primary inoculation, (2) lymphogenous extension, or (3) hematologic dissemination.⁴ According to a PubMed search of articles indexed for MEDLINE using the terms primary cutaneous Mycobacterium avium complex and MAC skin infection, only 11 known cases of primary cutaneous MAC infection have been reported in the English-language literature,^4-14  the most recent being a report by Landriscina et al.¹¹

A Runyon group III bacillus, MAC is a slow-growing nonchromogen that is ubiquitous in nature.¹⁵ It has been isolated from soil, water, house dust, vegetables, eggs, and milk. According to Reed et al,³ occupational exposure to soil is an independent risk factor for MAC infection, with individuals reporting more than 6 years of cumulative participation in lawn and landscaping services, farming, or other occupations involving substantial exposure to dirt or dust most likely to be MAC-positive. Cutaneous MAC infection may be associated with water exposure, as Sugita et al² described one familial outbreak of cutaneous MAC infection linked to use of a circulating, constantly heated bathwater system. With respect to US geography, individuals living in rural areas of the South seem most prone to MAC infection.³

Primary cutaneous infection with MAC occurs after a breach in the skin surface, though this fact may not be elicited by history. Modes of entry include minor abrasions after falling,¹ small wounds,² traumatic inoculation,¹⁵ and intramuscular injection.¹⁶ Clinically, cutaneous lesions of MAC are protean. In the literature, clinical presentation is described as a polymorphous appearance with scaling plaques, verrucous nodules, crusted ulcers, inflammatory nodules, dermatitis, panniculitis, draining sinuses, ecthymatous lesions, sporotrichoid growth patterns, or rosacealike papulopustules.^1,15,17 Lesions may affect the arms and legs, trunk, buttocks, and face.¹⁸

The differential diagnosis of MAC infection includes lupus vulgaris, Mycobacterium marinum infection (also known as swimming pool granuloma), sporotrichosis, nocardiosis, sarcoidosis, neutrophilic dermatosis, pyoderma gangrenosum, and cutaneous blastomycosis. Given its rarity and variability, diagnosis of MAC infection requires a high index of suspicion. Cutaneous MAC infection should be considered if a nodule, plaque, or ulcer fails to respond to conventional treatment, especially in patients with a history of environmental exposure and possible injury to the skin.

We report a rare case of primary cutaneous MAC infection arising in SCC excision sites in a patient without known immune deficiency. This presentation may have occurred for several reasons. First, the surgical excision sites coupled with the substantial occupational and recreational exposure to soil experienced by our patient may have served as portals for infection. Although SCCs are common on the hands, Mohs micrographic surgery is not always performed for excision; in our patient's case, this approach allowed for maximum tissue conservation and preserved manual function given the number and location of the lesions. Second, despite an overtly intact immune system, our patient may have harbored an occult immune deficiency, predisposing him to dermatologic infection with a microorganism of low intrinsic virulence and recurrent malignant neoplasms. This presentation may have been the first clinical indication of subtle immune compromise. For example, inadequate proinflammatory cytokines may contribute to both mycobacterial and malignant disease. A potential risk of inhibition of tumor necrosis factor α is the unmasking of tuberculosis or lymphoma.^19,20 Likewise, IFN-γ is vital in suppressing mycobacteria and malignancy. Yonekura et al²¹ found that IFN-γ induces apoptosis in oral SCC lines. It follows that a paucity of IFN-γ could allow neoplastic growth. Normal function of IFN-γ prompts microbicidal activity in macrophages and stimulates granuloma formation, both of which combat mycobacterial infection.¹⁹ A final postulation is that a simmering cutaneous MAC infection precipitated neoplastic degeneration into SCC, much the same way that the human papillomavirus has been correlated in the carcinogenesis of cervical cancer. As an intracellular microbe, MAC could cause the genetic machinery of skin cells to go awry. Kullavanijaya et al¹⁸ described a patient with cutaneous MAC in association with cervical cancer.

Conclusion

This association of primary cutaneous MAC infection and cutaneous malignancy in a reportedly immunocompetent patient is rare. Cancer patients, as noted by Feld et al,²² are 3 times more likely to develop infections with mycobacteria, with SCC, lymphoma, and leukemia being most commonly indicated. A specific immune deficit in the IFN-γ receptor is known to confer a selective predisposition to mycobacterial infection.^23,24 Toyoda et al²⁵ outlined the case of a pediatric patient with IFN-γ receptor 2 deficiency who presented with disseminated MAC infection and later succumbed to multiple SCCs of the hands and face. The authors' assertion was that inherited disorders of IFN-γ-mediated immunity may be associated with SCCs.²⁵ Unfortunately, our patient died before more specific immunological testing could be conducted. This case highlights the remarkable singularity of primary cutaneous MAC infection in association with multiple SCCs with seemingly intact immune status and offers some intriguing hypotheses regarding its occurrence.