Eccrine Carcinoma

Etiology

Although the precise etiology of eccrine carcinoma has not been determined, it has been associated with ultraviolet radiation exposure and immunosuppression.[5][6]

Epidemiology

Eccrine carcinoma is an extremely rare cutaneous malignancy, accounting for less than 0.01% of all cutaneous malignancies, and typically presents in the fifth to eighth decades of life.[1][7]

Histopathology

Sweat gland tumors are classified as eccrine, apocrine, mixed origin (eccrine and apocrine), or unclassifiable. In practice, however, most sweat gland tumors have both eccrine and apocrine components. Some tumors even exhibit complexity, with other lines of differentiation, namely follicular and/or sebaceous.[8] This differentiation is possibly due to the close embryological relationship between apocrine glands and pilosebaceous units. Histopathologies closely associated with eccrine carcinoma include hidradenocarcinoma, spiradenocarcinoma, and porocarcinoma.[2] 

Some relatively important and common types of eccrine carcinoma include porocarcinoma, syringoid carcinoma, ductal carcinoma, adenoid cystic carcinoma, and mucinous carcinoma.[9] Porocarcinomas are typically solid, lobular neoplastic masses with cystic changes and necrosis. Two types of atypical cells are present in porocarcinomas: eosinophilic and clear cells. These tumor cells are usually positive for cytokeratin and periodic acid-Schiff (PAS) stain.

Syringoid carcinoma demonstrates a mix of tubules, keratinizing cystic structures, solid islands, cellular cords, and desmoplastic stroma, with features resembling syringomas to some extent. Ductal carcinomas are characterized by tubular structures mixed with variable amounts of cellular cords. The degree of differentiation ranges from well to poorly differentiated. Tumor cells are typically positive for PAS, diastase-resistant PAS (D-PAS), and cytokeratins.[10]

Adenoid cystic carcinomas are composed of basaloid, monomorphous cells that are moderately atypical, with hyperchromatic nuclei and inconspicuous cytoplasm. Tumor cells are typically arranged in cribriform masses, islands, and tubular structures. Mucinous carcinomas are composed of cells arranged in solid islands, cribriform masses, tubules, and small nests, all embedded in large mucin pools.[9]

Immunohistochemistry (IHC) and molecular genetics have only a limited role in the diagnosis of sweat gland tumors; however, they can be useful in excluding other possible entities. One relevant entity to exclude is cutaneous metastases from visceral primary adenocarcinomas.[3] When pathological complexity is evident, and the pathologist cannot fit the case into any established category, they should render a descriptive diagnosis of a benign or malignant tumor with sweat gland differentiation.[11]

History and Physical

Eccrine carcinoma presents as a brown, bluish, erythematous nodule, papule, or ulcerative lesion. Although lesions can occur anywhere on the body, they most commonly involve the lower extremities (35%), followed by the head and neck (24%) and upper extremities (14%).[2][12]

A detailed history of the skin lesion should be obtained, including its onset, duration, and any changes in appearance. Notably, determining whether the tumor appeared de novo or developed from a preexisting visible or palpable skin lesion is important. Any associated pain, bleeding, discharge, or lymphadenopathy should be noted.

The history should also assess risk factors for skin cancer, including lifetime and occupational sun exposure and a history of severe childhood sunburns. Prior skin cancers and previous cryotherapy for indeterminate skin lesions should be elicited. In addition, the patient's overall medical history should be reviewed, with particular attention to autoimmune diseases, immunosuppressive conditions, immunosuppressive medications, and prior radiation therapy.

Physical examination should begin with evaluation of the lesion's location, size, and appearance, as well as the presence of satellite lesions or local lymph nodes. Palpation of the lesion is important for determining thickness and mobility versus fixation to underlying structures. A complete skin examination should be performed to evaluate for concurrent worrisome skin lesions.

Evaluation

Biopsy is the diagnostic test of choice for eccrine carcinoma. Histopathologic examination shows an infiltrative, moderately to poorly differentiated neoplasm arranged in a nested-to-trabecular pattern. Nuclei are relatively uniform with notably prominent nucleoli. The specific morphology depends on the distinct eccrine carcinoma entity. Relatively common types of eccrine carcinoma include porocarcinoma, syringoid carcinoma, ductal carcinoma, adenoid cystic carcinoma, and mucinous carcinoma.[9] IHC may be helpful in some cases; however, it is inconsistent. Markers that can support a diagnosis of eccrine carcinoma include carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), estrogen receptors (ER), progesterone receptors (PR), cytokeratin 7 (CK7), and pancytokeratins.[13][14]

Treatment / Management

Surgical excision with clear surgical margins is the treatment of choice for eccrine carcinoma.[8] Traditionally, wide surgical margins were advocated because of the tumor's infiltrative growth pattern; however, Mohs micrographic surgery has emerged as the preferred surgical standard, particularly in aesthetically sensitive areas.[15][16] Chemotherapy and radiation therapy have been used for metastatic lesions and for locations where complete surgical excision is not possible.[1] Because eccrine carcinoma is an infrequent entity, no randomized controlled trials have examined management options.(B3)

Differential Diagnosis

Eccrine carcinoma can resemble a variety of benign and malignant cutaneous lesions; therefore, the following conditions should be considered in the differential diagnosis:

• Basal cell carcinoma: Basal cell carcinoma (BCC) is the most common malignancy of the skin and constitutes up to 80% of all skin cancers. BCC occurs more commonly on sun-exposed skin. A papule or a nodule is the most common presentation of BCC. Morphologically, BCC appears as basaloid cells with scant cytoplasm and elongated hyperchromatic nuclei. Positive stains that aid in confirming the diagnosis include BerEP4, 34betaE12, MNF 116, p53, BCL2, and p63. Negative stains include EMA, CEA, involucrin, and CK20.[17]
• Squamous cell carcinoma: Squamous cell carcinoma (SCC) is the second most common skin malignancy. SCC is graded based on the degree of differentiation and keratinization into well, moderately, and poorly differentiated. Common presentations of SCC include a thin plaque or an erythematous scaly papule. Positive stains that aid in confirming the diagnosis include 34betaE12, AE1/AE3, CK5/6, EMA, and p63. Negative stains include CAM5.2, BerEP4, S100, and SMA.[18]
• Amelanotic melanoma: a variant of melanoma that presents as white or reddish lesions. Similar to other common skin malignancies, amelanotic melanoma is more common on sun-exposed skin. As with malignant melanoma, the prognosis of amelanotic melanoma is determined by lesion thickness and the extent of invasion.
• Seborrheic keratosis: a benign skin lesion that primarily affects adults. Clinically, it presents as a sharply demarcated, pigmented, and greasy lesion that protrudes above the skin surface. On microscopic examination, the lesion appears as acanthotic proliferations of small cuboidal keratinocytes without any evidence of cytological atypia.[19]
• Cutaneous lymphoma
• Verruca vulgaris
• Metastatic carcinoma: Skin metastases from breast, lung, or kidney carcinoma should be considered in the differential diagnosis of eccrine carcinoma.[20]

Staging

Pathological TNM staging (pTNM) of eccrine carcinoma is as follows:

Primary Tumor (pT)

• pTX: Primary tumor not assessable
• pT0: No evidence of primary tumor
• pTis: Carcinoma in situ
• pT1: Tumor ≤2 cm in the largest dimension
  • pT1a: Limited to the dermis or ≤2 mm in thickness
  • pT1b: Limited to the dermis and >2 mm in thickness but not >6 mm in thickness
  • pT1c: Invading the subcutis and/or >6 mm in thickness

• pT2: Tumor >2 cm but not >5 cm in its greatest dimension
  • pT2a: Limited to the dermis or ≤2 mm in thickness
  • pT2b: Limited to the dermis and >2 mm in thickness but not >6 mm in thickness
  • pT2c: Invading the subcutis and/or >6 mm in thickness

• pT3: Tumor >5 cm in its greatest dimension
  • pT3a: Limited to the dermis or ≤2 mm in thickness
  • pT3b: Limited to the dermis and >2 mm in thickness but not >6 mm in thickness
  • pT3c: Invading the subcutis and/or >6 mm in thickness

• pT4: Tumor invades the deep extradermal tissue (eg, cartilage, skeletal muscle, or bone)
  • pT4a: ≤6 mm in thickness
  • pT4b: >6 mm in thickness [11]

Regional Lymph Nodes (pN)

• pNX: Regional lymph nodes not assessable
• pN0: No regional lymph node metastasis
• pN1: Regional lymph node metastasis

Distant Metastasis (pM)

• pMX: Presence of distant metastasis not assessable
• pM1: Distant metastasis

Prognosis

The prognosis varies greatly with the stage of disease. Early-stage disease (stages 1 and 2) is associated with the best prognosis, with 5-year survival ranging from 76% to 82%.[21] Distant metastases present a very grim prognosis, with 10-year survival rates dropping to 9%.[2][21]

Complications

Complications of eccrine carcinoma include local recurrence (up to 20%) and distant metastases.[4] Other complications depend on the site of the tumor itself and effects on surrounding structures potentially involved by the tumor or affected by treatment. Distortion of surrounding facial structures by surgical reconstruction (eyelids, nose, auricles, and lips) or by radiation exposure is a primary concern. Exposure of underlying tissue layers (muscles, tendons, and bones) due to wound dehiscence or breakdown can occur in any area of the body.