Sameera Husain, MD

The Diagnosis: Glomangiomyoma

The nail unit excision specimen showed collections of cuboidal cells and spindled cells within the corium that were consistent with a diagnosis of a glomangiomyoma, a rare glomus tumor variant (Figure). Glomus tumors are benign neoplasms comprising glomus bodies, which are arteriovenous anastomoses involved in thermoregulation.¹ They develop in areas densely populated by glomus bodies, including the fingers, toes, and subungual areas. Glomus tumors most commonly develop in middle-aged women.² Clinically, they manifest with a characteristic triad of intense pain, point tenderness, and cold sensitivity and may appear as reddish-pink or blue macules under the nail plate and/or longitudinal erythronychia.^2-6 The presence of multiple glomus tumors is associated with neurofibromatosis type 1.⁷ 

Advanced imaging including ultrasonography and magnetic resonance imaging (MRI) may help confirm the diagnosis but may not be cost effective, as excision with histopathology is needed to relieve symptoms and render a definitive diagnosis. Radiography is highly insensitive in identifying bone erosions associated with glomus tumors.⁸ With ultrasonography, glomus tumors appear hypoechoic; with Doppler ultrasonography, they appear hypervascular. With MRI, glomus tumors appear as well-defined nodular lesions with hypointense signal intensity on T1-weighted sequence and hyperintense signal intensity on T2-weighted sequence, with strong enhancement using gadolinium-based contrast.^9,10 On histopathology, a glomus tumor appears as a nodular tumor with sheets of oval-nucleated cells arranged in multicellular layers surrounding blood vessels and are immunoreactive for α-smooth muscle actin, muscle-specific actin, and type IV collagen.^11,12 

There are several glomus tumor variants. The most common is a solid glomus tumor, which predominantly is composed of glomus cells, followed by glomangioma, which mainly is composed of blood vessels. Glomangiomyoma, which mostly is composed of smooth muscle cells, is the rarest variant.¹³ 

While glomus tumors are common in the subungual areas, it is an uncommon location for glomangiomyomas, which have been reported in the nail unit in only 7 prior case reports identified through searches of PubMed and Google Scholar using the terms glomangiomyoma, glomangiomyoma nail, and subungual glomangiomyoma (Table).^13-19 Glomangiomyomas more commonly are described in solid organs, including the stomach, kidney, pancreas, and bladder.¹⁶ The mean age of patients with subungual glomangiomyomas, including our patient, was 40.4 years (range, 3-61 years), with the majority being female (75.0% [6/8]). Most patients presented with fingernail involvement (75.0% [6/8]), nail dystrophy (eg, nail plate thinning, longitudinal grooves, splinter hemorrhages, longitudinal erythronychia)(62.5% [5/8]), and intermittent pain and/or point tenderness in the affected nail (75.0% [6/8]).^13-19 Notably, only our patient had longitudinal erythronychia as a clinical feature, and only one other case described MRI findings, which included a lobulated mass with intense contrast and distal phalanx destruction.¹⁸ One patient was a 3-year-old girl with a family history of generalized multiple glomangiomyomas. Although subungual glomangiomyoma was not confirmed on histopathology, the diagnosis in this patient was presumed based on her family history.¹³ On histopathology, glomangiomyomas are composed of oval-nucleated cells surrounding blood vessels. These oval-nucleated cells then gradually transition to smooth muscle cells.²⁰ 

A myxoid cyst is composed of a pseudocyst, which lacks a cyst lining, and is a result of synovial fluid from the distal interphalangeal joint entering the pseudocyst space.² It typically manifests with a longitudinal groove in the nail plate. A flesh-colored nodule may be appreciated between the cuticle and the distal interphalangeal joint.² The depth of the longitudinal groove may vary depending on the volume of synovial fluid within the myxoid cyst.²¹ In a series of 35 cases of subungual myxoid cysts, none manifested with longitudinal erythronychia. Due to their composition, myxoid cysts can be distinguished easily from solid tumors of the nail unit via transillumination.²² Pain is a much less common with myxoid cysts vs glomus tumors, as the filling of the pseudocyst space with synovial fluid typically is gradual, allowing the surrounding tissue to accommodate and adapt over time.²¹ In equivocal cases, MRI or high-resolution ultrasonography may be used to distinguish myxoid cysts and glomus tumors.⁸ Histopathology shows accumulation of mucin in the dermis with surrounding fibrous stroma.²³

Subungual neuromas are painful benign tumors that develop due to disorganized neural proliferation following disruption to peripheral nerves secondary to trauma or surgery. In 3 case reports, subungual neuromas manifested as painful subungual nodules, with proximal nail plate ridging, or onycholysis.^24-26 Since neuromas have only rarely been described in the subungual region, reports of MRI and ultrasonography findings are unknown. Histopathology is needed to distinguish neuromas from glomus tumors. Histopathology shows an acapsular structure consisting of disorganized spindle-cell proliferation and nerve fibers arranged in a tangle of fascicles within fibrotic tissue.²⁵ On immunochemistry, spindle cells typically are positive for cellular antigen protein S100.²⁶ 

Leiomyomas are benign neoplasms derived from smooth muscle, typically localized to the uterus or gastrointestinal tract, and have been described rarely in the nail unit.^27,28 It is hypothesized that subungual leiomyomas originate from the vascular smooth muscle in the subcutaneous layer of the nail unit.²⁸ Like glomus tumors, leiomyomas of the subungual region often manifest with pain and longitudinal erythronychia.^27-30 Subungual leiomyomas may be distinguished from glomus tumors via advanced imaging techniques, including ultrasonography and MRI. Cutaneous leiomyomas have been described with mild to moderate internal low flow vascularity on Doppler ultrasonography, while glomus tumors typically reveal high internal vascularity.²⁸ Biopsy with histopathology is needed for definitive diagnosis. On histopathology, leiomyomas demonstrate bland-appearing spindle-shaped cells with elongated nuclei arranged in fascicles.²⁷ They typically are positive for α-smooth muscle actin and caldesmon on immunostaining. 

Eccrine spiradenomas are benign adnexal tumors likely of apocrine origin with limited case reports in the literature.^31,32 Clinically, eccrine spiradenomas involving the nail unit may manifest with longitudinal nail splitting of the nail or as a papule on the proximal nail fold, with associated tenderness.^31,32 In a report of a 50-year-old woman with a histopathologically confirmed eccrine spiradenoma manifesting with longitudinal splitting of the nail and pain in the proximal nail fold, the mass appeared hypoechoic on ultrasonography with increased intramass vascularity on Doppler, while MRI showed an intensely enhancing lesion.³¹ These imaging features, combined with a classically manifesting feature of pain, make eccrine spiradenomas difficult to distinguish from glomus tumors; therefore, histopathologic examination can provide a definitive diagnosis, and surgical excision is used for treatment.³¹ On histopathology, these tumors are well circumscribed and composed of both small dark basaloid cells with peripheral compact nuclei and larger cells with central pale nuclei, which may be arranged in tubules.^31,32

The Diagnosis: Glomangiomyoma

The nail unit excision specimen showed collections of cuboidal cells and spindled cells within the corium that were consistent with a diagnosis of a glomangiomyoma, a rare glomus tumor variant (Figure). Glomus tumors are benign neoplasms comprising glomus bodies, which are arteriovenous anastomoses involved in thermoregulation.¹ They develop in areas densely populated by glomus bodies, including the fingers, toes, and subungual areas. Glomus tumors most commonly develop in middle-aged women.² Clinically, they manifest with a characteristic triad of intense pain, point tenderness, and cold sensitivity and may appear as reddish-pink or blue macules under the nail plate and/or longitudinal erythronychia.^2-6 The presence of multiple glomus tumors is associated with neurofibromatosis type 1.⁷ 

Advanced imaging including ultrasonography and magnetic resonance imaging (MRI) may help confirm the diagnosis but may not be cost effective, as excision with histopathology is needed to relieve symptoms and render a definitive diagnosis. Radiography is highly insensitive in identifying bone erosions associated with glomus tumors.⁸ With ultrasonography, glomus tumors appear hypoechoic; with Doppler ultrasonography, they appear hypervascular. With MRI, glomus tumors appear as well-defined nodular lesions with hypointense signal intensity on T1-weighted sequence and hyperintense signal intensity on T2-weighted sequence, with strong enhancement using gadolinium-based contrast.^9,10 On histopathology, a glomus tumor appears as a nodular tumor with sheets of oval-nucleated cells arranged in multicellular layers surrounding blood vessels and are immunoreactive for α-smooth muscle actin, muscle-specific actin, and type IV collagen.^11,12 

There are several glomus tumor variants. The most common is a solid glomus tumor, which predominantly is composed of glomus cells, followed by glomangioma, which mainly is composed of blood vessels. Glomangiomyoma, which mostly is composed of smooth muscle cells, is the rarest variant.¹³ 

While glomus tumors are common in the subungual areas, it is an uncommon location for glomangiomyomas, which have been reported in the nail unit in only 7 prior case reports identified through searches of PubMed and Google Scholar using the terms glomangiomyoma, glomangiomyoma nail, and subungual glomangiomyoma (Table).^13-19 Glomangiomyomas more commonly are described in solid organs, including the stomach, kidney, pancreas, and bladder.¹⁶ The mean age of patients with subungual glomangiomyomas, including our patient, was 40.4 years (range, 3-61 years), with the majority being female (75.0% [6/8]). Most patients presented with fingernail involvement (75.0% [6/8]), nail dystrophy (eg, nail plate thinning, longitudinal grooves, splinter hemorrhages, longitudinal erythronychia)(62.5% [5/8]), and intermittent pain and/or point tenderness in the affected nail (75.0% [6/8]).^13-19 Notably, only our patient had longitudinal erythronychia as a clinical feature, and only one other case described MRI findings, which included a lobulated mass with intense contrast and distal phalanx destruction.¹⁸ One patient was a 3-year-old girl with a family history of generalized multiple glomangiomyomas. Although subungual glomangiomyoma was not confirmed on histopathology, the diagnosis in this patient was presumed based on her family history.¹³ On histopathology, glomangiomyomas are composed of oval-nucleated cells surrounding blood vessels. These oval-nucleated cells then gradually transition to smooth muscle cells.²⁰ 

A myxoid cyst is composed of a pseudocyst, which lacks a cyst lining, and is a result of synovial fluid from the distal interphalangeal joint entering the pseudocyst space.² It typically manifests with a longitudinal groove in the nail plate. A flesh-colored nodule may be appreciated between the cuticle and the distal interphalangeal joint.² The depth of the longitudinal groove may vary depending on the volume of synovial fluid within the myxoid cyst.²¹ In a series of 35 cases of subungual myxoid cysts, none manifested with longitudinal erythronychia. Due to their composition, myxoid cysts can be distinguished easily from solid tumors of the nail unit via transillumination.²² Pain is a much less common with myxoid cysts vs glomus tumors, as the filling of the pseudocyst space with synovial fluid typically is gradual, allowing the surrounding tissue to accommodate and adapt over time.²¹ In equivocal cases, MRI or high-resolution ultrasonography may be used to distinguish myxoid cysts and glomus tumors.⁸ Histopathology shows accumulation of mucin in the dermis with surrounding fibrous stroma.²³

Subungual neuromas are painful benign tumors that develop due to disorganized neural proliferation following disruption to peripheral nerves secondary to trauma or surgery. In 3 case reports, subungual neuromas manifested as painful subungual nodules, with proximal nail plate ridging, or onycholysis.^24-26 Since neuromas have only rarely been described in the subungual region, reports of MRI and ultrasonography findings are unknown. Histopathology is needed to distinguish neuromas from glomus tumors. Histopathology shows an acapsular structure consisting of disorganized spindle-cell proliferation and nerve fibers arranged in a tangle of fascicles within fibrotic tissue.²⁵ On immunochemistry, spindle cells typically are positive for cellular antigen protein S100.²⁶ 

Leiomyomas are benign neoplasms derived from smooth muscle, typically localized to the uterus or gastrointestinal tract, and have been described rarely in the nail unit.^27,28 It is hypothesized that subungual leiomyomas originate from the vascular smooth muscle in the subcutaneous layer of the nail unit.²⁸ Like glomus tumors, leiomyomas of the subungual region often manifest with pain and longitudinal erythronychia.^27-30 Subungual leiomyomas may be distinguished from glomus tumors via advanced imaging techniques, including ultrasonography and MRI. Cutaneous leiomyomas have been described with mild to moderate internal low flow vascularity on Doppler ultrasonography, while glomus tumors typically reveal high internal vascularity.²⁸ Biopsy with histopathology is needed for definitive diagnosis. On histopathology, leiomyomas demonstrate bland-appearing spindle-shaped cells with elongated nuclei arranged in fascicles.²⁷ They typically are positive for α-smooth muscle actin and caldesmon on immunostaining. 

Eccrine spiradenomas are benign adnexal tumors likely of apocrine origin with limited case reports in the literature.^31,32 Clinically, eccrine spiradenomas involving the nail unit may manifest with longitudinal nail splitting of the nail or as a papule on the proximal nail fold, with associated tenderness.^31,32 In a report of a 50-year-old woman with a histopathologically confirmed eccrine spiradenoma manifesting with longitudinal splitting of the nail and pain in the proximal nail fold, the mass appeared hypoechoic on ultrasonography with increased intramass vascularity on Doppler, while MRI showed an intensely enhancing lesion.³¹ These imaging features, combined with a classically manifesting feature of pain, make eccrine spiradenomas difficult to distinguish from glomus tumors; therefore, histopathologic examination can provide a definitive diagnosis, and surgical excision is used for treatment.³¹ On histopathology, these tumors are well circumscribed and composed of both small dark basaloid cells with peripheral compact nuclei and larger cells with central pale nuclei, which may be arranged in tubules.^31,32

The Diagnosis: Glomangiomyoma

The nail unit excision specimen showed collections of cuboidal cells and spindled cells within the corium that were consistent with a diagnosis of a glomangiomyoma, a rare glomus tumor variant (Figure). Glomus tumors are benign neoplasms comprising glomus bodies, which are arteriovenous anastomoses involved in thermoregulation.¹ They develop in areas densely populated by glomus bodies, including the fingers, toes, and subungual areas. Glomus tumors most commonly develop in middle-aged women.² Clinically, they manifest with a characteristic triad of intense pain, point tenderness, and cold sensitivity and may appear as reddish-pink or blue macules under the nail plate and/or longitudinal erythronychia.^2-6 The presence of multiple glomus tumors is associated with neurofibromatosis type 1.⁷ 

Advanced imaging including ultrasonography and magnetic resonance imaging (MRI) may help confirm the diagnosis but may not be cost effective, as excision with histopathology is needed to relieve symptoms and render a definitive diagnosis. Radiography is highly insensitive in identifying bone erosions associated with glomus tumors.⁸ With ultrasonography, glomus tumors appear hypoechoic; with Doppler ultrasonography, they appear hypervascular. With MRI, glomus tumors appear as well-defined nodular lesions with hypointense signal intensity on T1-weighted sequence and hyperintense signal intensity on T2-weighted sequence, with strong enhancement using gadolinium-based contrast.^9,10 On histopathology, a glomus tumor appears as a nodular tumor with sheets of oval-nucleated cells arranged in multicellular layers surrounding blood vessels and are immunoreactive for α-smooth muscle actin, muscle-specific actin, and type IV collagen.^11,12 

There are several glomus tumor variants. The most common is a solid glomus tumor, which predominantly is composed of glomus cells, followed by glomangioma, which mainly is composed of blood vessels. Glomangiomyoma, which mostly is composed of smooth muscle cells, is the rarest variant.¹³ 

While glomus tumors are common in the subungual areas, it is an uncommon location for glomangiomyomas, which have been reported in the nail unit in only 7 prior case reports identified through searches of PubMed and Google Scholar using the terms glomangiomyoma, glomangiomyoma nail, and subungual glomangiomyoma (Table).^13-19 Glomangiomyomas more commonly are described in solid organs, including the stomach, kidney, pancreas, and bladder.¹⁶ The mean age of patients with subungual glomangiomyomas, including our patient, was 40.4 years (range, 3-61 years), with the majority being female (75.0% [6/8]). Most patients presented with fingernail involvement (75.0% [6/8]), nail dystrophy (eg, nail plate thinning, longitudinal grooves, splinter hemorrhages, longitudinal erythronychia)(62.5% [5/8]), and intermittent pain and/or point tenderness in the affected nail (75.0% [6/8]).^13-19 Notably, only our patient had longitudinal erythronychia as a clinical feature, and only one other case described MRI findings, which included a lobulated mass with intense contrast and distal phalanx destruction.¹⁸ One patient was a 3-year-old girl with a family history of generalized multiple glomangiomyomas. Although subungual glomangiomyoma was not confirmed on histopathology, the diagnosis in this patient was presumed based on her family history.¹³ On histopathology, glomangiomyomas are composed of oval-nucleated cells surrounding blood vessels. These oval-nucleated cells then gradually transition to smooth muscle cells.²⁰ 

A myxoid cyst is composed of a pseudocyst, which lacks a cyst lining, and is a result of synovial fluid from the distal interphalangeal joint entering the pseudocyst space.² It typically manifests with a longitudinal groove in the nail plate. A flesh-colored nodule may be appreciated between the cuticle and the distal interphalangeal joint.² The depth of the longitudinal groove may vary depending on the volume of synovial fluid within the myxoid cyst.²¹ In a series of 35 cases of subungual myxoid cysts, none manifested with longitudinal erythronychia. Due to their composition, myxoid cysts can be distinguished easily from solid tumors of the nail unit via transillumination.²² Pain is a much less common with myxoid cysts vs glomus tumors, as the filling of the pseudocyst space with synovial fluid typically is gradual, allowing the surrounding tissue to accommodate and adapt over time.²¹ In equivocal cases, MRI or high-resolution ultrasonography may be used to distinguish myxoid cysts and glomus tumors.⁸ Histopathology shows accumulation of mucin in the dermis with surrounding fibrous stroma.²³

Subungual neuromas are painful benign tumors that develop due to disorganized neural proliferation following disruption to peripheral nerves secondary to trauma or surgery. In 3 case reports, subungual neuromas manifested as painful subungual nodules, with proximal nail plate ridging, or onycholysis.^24-26 Since neuromas have only rarely been described in the subungual region, reports of MRI and ultrasonography findings are unknown. Histopathology is needed to distinguish neuromas from glomus tumors. Histopathology shows an acapsular structure consisting of disorganized spindle-cell proliferation and nerve fibers arranged in a tangle of fascicles within fibrotic tissue.²⁵ On immunochemistry, spindle cells typically are positive for cellular antigen protein S100.²⁶ 

Leiomyomas are benign neoplasms derived from smooth muscle, typically localized to the uterus or gastrointestinal tract, and have been described rarely in the nail unit.^27,28 It is hypothesized that subungual leiomyomas originate from the vascular smooth muscle in the subcutaneous layer of the nail unit.²⁸ Like glomus tumors, leiomyomas of the subungual region often manifest with pain and longitudinal erythronychia.^27-30 Subungual leiomyomas may be distinguished from glomus tumors via advanced imaging techniques, including ultrasonography and MRI. Cutaneous leiomyomas have been described with mild to moderate internal low flow vascularity on Doppler ultrasonography, while glomus tumors typically reveal high internal vascularity.²⁸ Biopsy with histopathology is needed for definitive diagnosis. On histopathology, leiomyomas demonstrate bland-appearing spindle-shaped cells with elongated nuclei arranged in fascicles.²⁷ They typically are positive for α-smooth muscle actin and caldesmon on immunostaining. 

Eccrine spiradenomas are benign adnexal tumors likely of apocrine origin with limited case reports in the literature.^31,32 Clinically, eccrine spiradenomas involving the nail unit may manifest with longitudinal nail splitting of the nail or as a papule on the proximal nail fold, with associated tenderness.^31,32 In a report of a 50-year-old woman with a histopathologically confirmed eccrine spiradenoma manifesting with longitudinal splitting of the nail and pain in the proximal nail fold, the mass appeared hypoechoic on ultrasonography with increased intramass vascularity on Doppler, while MRI showed an intensely enhancing lesion.³¹ These imaging features, combined with a classically manifesting feature of pain, make eccrine spiradenomas difficult to distinguish from glomus tumors; therefore, histopathologic examination can provide a definitive diagnosis, and surgical excision is used for treatment.³¹ On histopathology, these tumors are well circumscribed and composed of both small dark basaloid cells with peripheral compact nuclei and larger cells with central pale nuclei, which may be arranged in tubules.^31,32

The Diagnosis: Nodular Hidradenoma

Nodular hidradenomas (NHs) are rare benign cutaneous adnexal neoplasms first described in 1949 as clear cell papillary carcinomas.¹ Since then, various terms have been used to describe this entity, such as eccrine acrospiroma, solid-cystic hidradenoma, and clear cell hidradenoma.² Review of the literature revealed a female predominance (2:1 ratio) and a mean age at presentation of 37.2 years.^3,4 Nodular hidradenoma presents as an asymptomatic, solitary, mobile, firm nodule with intact overlying skin. Rarely, multiple nodules may occur.³ Some tumors display ulceration and serous fluid leakage.⁵ They occur most commonly on the scalp, face, and upper extremities with an average size of 2 cm.³ Rapid growth of the tumor may signal a malignant change.⁶

Histopathology reveals a lobulated, circumscribed, symmetrical tumor with dermal nests of epithelial cells that are polygonal with eosinophilic cytoplasm forming ductlike spaces (Figure). However, clear cell changes and squamous differentiation may be prominent features. Cystic spaces may result from tumor cell degeneration. Most tumors are encased by collagenous fibrous tissue and rarely have epidermal attachments.³

Anastomosing aggregates of squamous cells forming ductlike spaces were viewed on low-power magnification (A)(H&E, original magnification ×10). On higher power there were ductlike spaces and eosinophilic hyalinized stroma entrapped by the bland-appearing squamous proliferation (B)(H&E, original magnification ×20).

Nodular hidradenoma traditionally has been considered to be of eccrine origin, but more recent literature indicates that the majority of NHs are of apocrine origin. Histologically, apocrine tumors display eosinophilic secretion, mucinous epithelium, squamous or sebaceous differentiation, and decapitation secretion, whereas eccrine tumors are identified by their lack of specific features.³

Nodular hidradenoma may recur after excision. Malignant transformation is rare. In one review, 6.7% (6/89) of NHs were malignant, characterized by abnormal mitoses, nuclear atypia, and necrosis.⁴ Malignant NH or nodular hidradenocarcinoma behaves aggressively with up to an 86% local recurrence and 60% rate of metastasis within 2 years.⁶ Survival time is inversely proportional to the size of the tumor and is generally poor, with a 5-year disease-free survival of less than 30%.^6,7

Treatment of NH is achieved through primary excision or Mohs micrographic surgery; however, treatment of nodular hidradenocarcinoma is controversial and typically begins with wide local excision but may involve lymph node dissection if necessary. Use of adjuvant chemotherapy and radiation therapy for metastases warrants more clinical studies, as it is a rare occurrence.⁶ Our patient planned to undergo a total excision of the benign nodule once she healed from the biopsy; however, she was lost to follow-up, as she moved out of state.

The Diagnosis: Nodular Hidradenoma

Nodular hidradenomas (NHs) are rare benign cutaneous adnexal neoplasms first described in 1949 as clear cell papillary carcinomas.¹ Since then, various terms have been used to describe this entity, such as eccrine acrospiroma, solid-cystic hidradenoma, and clear cell hidradenoma.² Review of the literature revealed a female predominance (2:1 ratio) and a mean age at presentation of 37.2 years.^3,4 Nodular hidradenoma presents as an asymptomatic, solitary, mobile, firm nodule with intact overlying skin. Rarely, multiple nodules may occur.³ Some tumors display ulceration and serous fluid leakage.⁵ They occur most commonly on the scalp, face, and upper extremities with an average size of 2 cm.³ Rapid growth of the tumor may signal a malignant change.⁶

Histopathology reveals a lobulated, circumscribed, symmetrical tumor with dermal nests of epithelial cells that are polygonal with eosinophilic cytoplasm forming ductlike spaces (Figure). However, clear cell changes and squamous differentiation may be prominent features. Cystic spaces may result from tumor cell degeneration. Most tumors are encased by collagenous fibrous tissue and rarely have epidermal attachments.³

Anastomosing aggregates of squamous cells forming ductlike spaces were viewed on low-power magnification (A)(H&E, original magnification ×10). On higher power there were ductlike spaces and eosinophilic hyalinized stroma entrapped by the bland-appearing squamous proliferation (B)(H&E, original magnification ×20).

Nodular hidradenoma traditionally has been considered to be of eccrine origin, but more recent literature indicates that the majority of NHs are of apocrine origin. Histologically, apocrine tumors display eosinophilic secretion, mucinous epithelium, squamous or sebaceous differentiation, and decapitation secretion, whereas eccrine tumors are identified by their lack of specific features.³

Nodular hidradenoma may recur after excision. Malignant transformation is rare. In one review, 6.7% (6/89) of NHs were malignant, characterized by abnormal mitoses, nuclear atypia, and necrosis.⁴ Malignant NH or nodular hidradenocarcinoma behaves aggressively with up to an 86% local recurrence and 60% rate of metastasis within 2 years.⁶ Survival time is inversely proportional to the size of the tumor and is generally poor, with a 5-year disease-free survival of less than 30%.^6,7

Treatment of NH is achieved through primary excision or Mohs micrographic surgery; however, treatment of nodular hidradenocarcinoma is controversial and typically begins with wide local excision but may involve lymph node dissection if necessary. Use of adjuvant chemotherapy and radiation therapy for metastases warrants more clinical studies, as it is a rare occurrence.⁶ Our patient planned to undergo a total excision of the benign nodule once she healed from the biopsy; however, she was lost to follow-up, as she moved out of state.

The Diagnosis: Nodular Hidradenoma

Nodular hidradenomas (NHs) are rare benign cutaneous adnexal neoplasms first described in 1949 as clear cell papillary carcinomas.¹ Since then, various terms have been used to describe this entity, such as eccrine acrospiroma, solid-cystic hidradenoma, and clear cell hidradenoma.² Review of the literature revealed a female predominance (2:1 ratio) and a mean age at presentation of 37.2 years.^3,4 Nodular hidradenoma presents as an asymptomatic, solitary, mobile, firm nodule with intact overlying skin. Rarely, multiple nodules may occur.³ Some tumors display ulceration and serous fluid leakage.⁵ They occur most commonly on the scalp, face, and upper extremities with an average size of 2 cm.³ Rapid growth of the tumor may signal a malignant change.⁶

Histopathology reveals a lobulated, circumscribed, symmetrical tumor with dermal nests of epithelial cells that are polygonal with eosinophilic cytoplasm forming ductlike spaces (Figure). However, clear cell changes and squamous differentiation may be prominent features. Cystic spaces may result from tumor cell degeneration. Most tumors are encased by collagenous fibrous tissue and rarely have epidermal attachments.³

Anastomosing aggregates of squamous cells forming ductlike spaces were viewed on low-power magnification (A)(H&E, original magnification ×10). On higher power there were ductlike spaces and eosinophilic hyalinized stroma entrapped by the bland-appearing squamous proliferation (B)(H&E, original magnification ×20).

Nodular hidradenoma traditionally has been considered to be of eccrine origin, but more recent literature indicates that the majority of NHs are of apocrine origin. Histologically, apocrine tumors display eosinophilic secretion, mucinous epithelium, squamous or sebaceous differentiation, and decapitation secretion, whereas eccrine tumors are identified by their lack of specific features.³

Nodular hidradenoma may recur after excision. Malignant transformation is rare. In one review, 6.7% (6/89) of NHs were malignant, characterized by abnormal mitoses, nuclear atypia, and necrosis.⁴ Malignant NH or nodular hidradenocarcinoma behaves aggressively with up to an 86% local recurrence and 60% rate of metastasis within 2 years.⁶ Survival time is inversely proportional to the size of the tumor and is generally poor, with a 5-year disease-free survival of less than 30%.^6,7

Treatment of NH is achieved through primary excision or Mohs micrographic surgery; however, treatment of nodular hidradenocarcinoma is controversial and typically begins with wide local excision but may involve lymph node dissection if necessary. Use of adjuvant chemotherapy and radiation therapy for metastases warrants more clinical studies, as it is a rare occurrence.⁶ Our patient planned to undergo a total excision of the benign nodule once she healed from the biopsy; however, she was lost to follow-up, as she moved out of state.

The Diagnosis: Mycobacterium chelonae Arising Within a Tattoo

A 3-mm punch biopsy specimen was obtained from one of the plaques. Histopathology revealed an unremarkable epidermis with granulomatous collections of epithelioid histiocytes in association with neutrophils and lymphocytes in the dermis (Figure 1). Periodic acid–Schiff stain was negative for fungal organisms. Gram stain was negative for bacteria. Fite stain was positive for acid-fast bacilli (Figure 2). Clinical and histopathologic findings led to the initial diagnosis of a mycobacterial infection within the tattoo. The patient was empirically started on oral doxycycline 100 mg twice daily and oral clarithromycin 500 mg twice daily with mild improvement of the lesions over the next month. After 6 weeks the mycobacterial cultures were persistently negative and high-performance liquid chromatography was performed verifying the presence of Mycobacterium chelonae. Clarithromycin was continued and the doxycycline was replaced with oral trimethoprim-sulfamethoxazole (double strength) twice daily due to resistance. The patient was referred to an infectious disease specialist who concurred with the treatment regimen for a duration of 6 months to a year. A chest radiograph also was performed to rule out disseminated disease. Several months later the patient’s close friend presented with a similar infection that was acquired on the same day as our patient at the same tattoo parlor. The New York City Department of Health and Mental Hygiene was notified about these cases and informed us of other cases in New York State linked to contaminated tattoo ink.

Figure 1. Granulomatous collections of epithelioid histiocytes with neutrophilic and lymphocytic infiltrates in the dermis (H&E, original magnification ×4). Figure 2. Acid-fast organisms in the dermis (Fite, original magnification ×100).

Mycobacterium chelonae is a rapidly growing nontuberculous mycobacteria (Runyon group IV) that is found in nature and contaminated sources such as soil, lakes, sewage, and tap water.¹ Inoculation ofM chelonae through contaminated instruments leads to the formation of painful lesions, abscesses, fistulas, and granulomas that are extremely difficult to treat.² In our patient, M chelonae was most likely transmitted via contaminated tap water that was used to dilute the black tattoo ink to yield a gray color. Alternative sources are the ink itself or the container used to mix the ink.³Mycobacterium chelonae can cause infections in the skin, lungs, joints, bones, and eyes.⁴ With the exception of lung disease, trauma is the usual inciting factor. Disseminated infections are almost exclusively found in immunosuppressed individuals. Mycobacterium chelonae is typically found to grow on culture within 7 days. However, in our case there was no growth after 6 weeks of incubation. High-performance liquid chromatography analysis of mycolic acid is an alternative method of identifying mycobacteria. This technique verified the presence of M chelonae in our case when cultures were persistently negative.⁵

Mycobacterium chelonae is difficult to treat. The most common antibiotics used for treatment are clarithromycin, azithromycin, doxycycline, and linezolid.⁶ Studies of various antibiotics have shown that clarithromycin is the most effective macrolide against M chelonae.⁷ Tetracyclines also were studied in their effectiveness at treating nontuberculous mycobacteria infections but were found to have increased resistance to M chelonae.⁸ Although treatment regimens vary, the highest success rates are achieved with a minimum of 6 months of therapy using at least 2 drugs. Longer treatment is recommended for immunocompromised individuals.⁹

The case we present is important from a public health perspective. The tattoo industry and ink manufacturers should bemade aware of the risks of various infections from nonsterile techniques. Tattoo parlor employees should be advised of the risks of using nonsterile water for ink dilution and cleaning tattoo equipment. They also should be continuously educated on aseptic techniques.

The Diagnosis: Mycobacterium chelonae Arising Within a Tattoo

A 3-mm punch biopsy specimen was obtained from one of the plaques. Histopathology revealed an unremarkable epidermis with granulomatous collections of epithelioid histiocytes in association with neutrophils and lymphocytes in the dermis (Figure 1). Periodic acid–Schiff stain was negative for fungal organisms. Gram stain was negative for bacteria. Fite stain was positive for acid-fast bacilli (Figure 2). Clinical and histopathologic findings led to the initial diagnosis of a mycobacterial infection within the tattoo. The patient was empirically started on oral doxycycline 100 mg twice daily and oral clarithromycin 500 mg twice daily with mild improvement of the lesions over the next month. After 6 weeks the mycobacterial cultures were persistently negative and high-performance liquid chromatography was performed verifying the presence of Mycobacterium chelonae. Clarithromycin was continued and the doxycycline was replaced with oral trimethoprim-sulfamethoxazole (double strength) twice daily due to resistance. The patient was referred to an infectious disease specialist who concurred with the treatment regimen for a duration of 6 months to a year. A chest radiograph also was performed to rule out disseminated disease. Several months later the patient’s close friend presented with a similar infection that was acquired on the same day as our patient at the same tattoo parlor. The New York City Department of Health and Mental Hygiene was notified about these cases and informed us of other cases in New York State linked to contaminated tattoo ink.

Figure 1. Granulomatous collections of epithelioid histiocytes with neutrophilic and lymphocytic infiltrates in the dermis (H&E, original magnification ×4). Figure 2. Acid-fast organisms in the dermis (Fite, original magnification ×100).

Mycobacterium chelonae is a rapidly growing nontuberculous mycobacteria (Runyon group IV) that is found in nature and contaminated sources such as soil, lakes, sewage, and tap water.¹ Inoculation ofM chelonae through contaminated instruments leads to the formation of painful lesions, abscesses, fistulas, and granulomas that are extremely difficult to treat.² In our patient, M chelonae was most likely transmitted via contaminated tap water that was used to dilute the black tattoo ink to yield a gray color. Alternative sources are the ink itself or the container used to mix the ink.³Mycobacterium chelonae can cause infections in the skin, lungs, joints, bones, and eyes.⁴ With the exception of lung disease, trauma is the usual inciting factor. Disseminated infections are almost exclusively found in immunosuppressed individuals. Mycobacterium chelonae is typically found to grow on culture within 7 days. However, in our case there was no growth after 6 weeks of incubation. High-performance liquid chromatography analysis of mycolic acid is an alternative method of identifying mycobacteria. This technique verified the presence of M chelonae in our case when cultures were persistently negative.⁵

Mycobacterium chelonae is difficult to treat. The most common antibiotics used for treatment are clarithromycin, azithromycin, doxycycline, and linezolid.⁶ Studies of various antibiotics have shown that clarithromycin is the most effective macrolide against M chelonae.⁷ Tetracyclines also were studied in their effectiveness at treating nontuberculous mycobacteria infections but were found to have increased resistance to M chelonae.⁸ Although treatment regimens vary, the highest success rates are achieved with a minimum of 6 months of therapy using at least 2 drugs. Longer treatment is recommended for immunocompromised individuals.⁹

The case we present is important from a public health perspective. The tattoo industry and ink manufacturers should bemade aware of the risks of various infections from nonsterile techniques. Tattoo parlor employees should be advised of the risks of using nonsterile water for ink dilution and cleaning tattoo equipment. They also should be continuously educated on aseptic techniques.

The Diagnosis: Mycobacterium chelonae Arising Within a Tattoo

A 3-mm punch biopsy specimen was obtained from one of the plaques. Histopathology revealed an unremarkable epidermis with granulomatous collections of epithelioid histiocytes in association with neutrophils and lymphocytes in the dermis (Figure 1). Periodic acid–Schiff stain was negative for fungal organisms. Gram stain was negative for bacteria. Fite stain was positive for acid-fast bacilli (Figure 2). Clinical and histopathologic findings led to the initial diagnosis of a mycobacterial infection within the tattoo. The patient was empirically started on oral doxycycline 100 mg twice daily and oral clarithromycin 500 mg twice daily with mild improvement of the lesions over the next month. After 6 weeks the mycobacterial cultures were persistently negative and high-performance liquid chromatography was performed verifying the presence of Mycobacterium chelonae. Clarithromycin was continued and the doxycycline was replaced with oral trimethoprim-sulfamethoxazole (double strength) twice daily due to resistance. The patient was referred to an infectious disease specialist who concurred with the treatment regimen for a duration of 6 months to a year. A chest radiograph also was performed to rule out disseminated disease. Several months later the patient’s close friend presented with a similar infection that was acquired on the same day as our patient at the same tattoo parlor. The New York City Department of Health and Mental Hygiene was notified about these cases and informed us of other cases in New York State linked to contaminated tattoo ink.

Figure 1. Granulomatous collections of epithelioid histiocytes with neutrophilic and lymphocytic infiltrates in the dermis (H&E, original magnification ×4). Figure 2. Acid-fast organisms in the dermis (Fite, original magnification ×100).

Mycobacterium chelonae is a rapidly growing nontuberculous mycobacteria (Runyon group IV) that is found in nature and contaminated sources such as soil, lakes, sewage, and tap water.¹ Inoculation ofM chelonae through contaminated instruments leads to the formation of painful lesions, abscesses, fistulas, and granulomas that are extremely difficult to treat.² In our patient, M chelonae was most likely transmitted via contaminated tap water that was used to dilute the black tattoo ink to yield a gray color. Alternative sources are the ink itself or the container used to mix the ink.³Mycobacterium chelonae can cause infections in the skin, lungs, joints, bones, and eyes.⁴ With the exception of lung disease, trauma is the usual inciting factor. Disseminated infections are almost exclusively found in immunosuppressed individuals. Mycobacterium chelonae is typically found to grow on culture within 7 days. However, in our case there was no growth after 6 weeks of incubation. High-performance liquid chromatography analysis of mycolic acid is an alternative method of identifying mycobacteria. This technique verified the presence of M chelonae in our case when cultures were persistently negative.⁵

Mycobacterium chelonae is difficult to treat. The most common antibiotics used for treatment are clarithromycin, azithromycin, doxycycline, and linezolid.⁶ Studies of various antibiotics have shown that clarithromycin is the most effective macrolide against M chelonae.⁷ Tetracyclines also were studied in their effectiveness at treating nontuberculous mycobacteria infections but were found to have increased resistance to M chelonae.⁸ Although treatment regimens vary, the highest success rates are achieved with a minimum of 6 months of therapy using at least 2 drugs. Longer treatment is recommended for immunocompromised individuals.⁹

The case we present is important from a public health perspective. The tattoo industry and ink manufacturers should bemade aware of the risks of various infections from nonsterile techniques. Tattoo parlor employees should be advised of the risks of using nonsterile water for ink dilution and cleaning tattoo equipment. They also should be continuously educated on aseptic techniques.