Continuing Education Activity

Eccrine carcinoma (EC) is a rare carcinoma that originates from the eccrine sweat glands of the skin and accounts for less than 0.01% of diagnosed cutaneous malignancies. Sweat gland tumors have been traditionally subdivided into four large groups: Eccrine, apocrine, mixed origin (eccrine and apocrine), and other un-classifiable sweat gland tumors. Eccrine tumors are divided into benign and malignant. This activity reviews the evaluation, differential, and treatment of sweat gland tumors and highlights the role of the interprofessional team in treating patients with this condition.

Objectives:

• Review the risk factors for sweat gland tumors.
• Describe the presentation of a patient with a sweat gland tumor.
• Summarize the treatment options for sweat gland tumors.
• Explain the importance of improving care coordination amongst the interprofessional team to enhance the delivery of care for patients with sweat gland tumors.

Introduction

Eccrine carcinoma (EC) is a rare carcinoma that originates from the eccrine sweat glands of the skin and accounts for less than 0.01% of diagnosed cutaneous malignancies.[1] Sweat gland tumors have traditionally subdivided into four broad groups: eccrine, apocrine, mixed origin (eccrine and apocrine), and other unclassifiable sweat gland tumors. Eccrine tumors further divide into benign and malignant. Benign entities include poroma, hidradenoma, spiradenoma, cylindroma, syringometaplasia, syringoma, syringofibroadenoma, and chondroid syringoma. Malignant eccrine carcinoma entities include porocarcinoma, hidradenocarcinoma, malignant spiradenoma carcinoma, malignant cylindroma, syringoid eccrine carcinoma, microcystic adnexal carcinoma, mucinous carcinoma, adenoid cystic carcinoma, and ductal papillary adenocarcinoma. Other un-classifiable sweat gland tumors include eccrine ductal carcinoma, basaloid eccrine carcinoma, clear cell eccrine carcinoma, and non-specified sweat gland carcinomas.

Malignant sweat gland tumors are heterogeneous neoplasms of different biological behavior.[2] The principal characteristic of these tumors is that they are locally aggressive and show a high rate of recurrence. Separation of eccrine carcinoma has traditionally been according to their behavior into low grade and high grade malignant.[3] Proper identification of eccrine carcinoma is sometimes challenging due to the morphological similarity to other common tumors and the lack of consistent immunohistochemical markers. 

Etiology

Research has not uncovered a clear etiology.

Epidemiology

Eccrine carcinoma is an extremely rare cutaneous malignancy that accounts for less than 0.01% of diagnosed cutaneous malignancies.[1]

Histopathology

Sweat gland tumors divide into eccrine, apocrine, mixed origin (eccrine and apocrine), and other un-classifiable sweat gland tumors. In real practice, most sweat gland tumors have both eccrine and apocrine components. Some even show complexity such as showing other lines of differentiation, namely follicular and/or sebaceous.[4] 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 porocarcinomas, syringoid carcinoma, ductal carcinomas, adenoid cystic carcinomas, and mucinous carcinomas.[5] Porocarcinomas are characteristically solid neoplastic lobular 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 PAS. Syringoid carcinoma shows a mix of tubules, keratinizing cystic structures, solid islands, cellular cords, and desmoplastic stroma, resembling syringomas to some extent. Ductal carcinomas characteristically demonstrate by the presence of tubular structures mixed with variable amounts of cellular cords. The degree of differentiation range from well to poorly differentiated. Tumor cells are positive for PAS, D-PAS and, cytokeratins.[6] Adenoid cystic carcinomas are morphologically composed of basaloid and monomorphous cells; moderately atypical with hyperchromatic nuclei and inconspicuous cytoplasm. Tumor cells typically arrange in cribriform masses, islands, and tubular structures. Mucinous carcinomas are morphologically composed of cells, arranged in solid islands, cribriform masses, tubules, and small nests embedded in large mucin pools.[5]

Immunohistochemistry and molecular genetics play only a minor role in the diagnosis of sweat gland tumors, however, 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 to any established category, they should render a descriptive diagnosis of benign/malignant tumor with sweat gland differentiation.[7]

History and Physical

EC presents as a brown, bluish, erythematous nodule, papule, or ulcerative lesion. Lesions can present anywhere in the body. However, the lower extremities (35%), head and neck (24%), and upper extremities (14%) are common regions.[2][8]

Evaluation

The test of choice in the diagnosis of eccrine carcinoma is a skin biopsy. The biopsy will show infiltrative, moderately to poorly differentiated neoplasm in a nested to the 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 porocarcinomas, syringoid carcinoma, ductal carcinomas, adenoid cystic carcinomas, and mucinous carcinomas.[5] Immunohistochemistry (IHC) may be helpful in some cases; however, it is inconsistent. Markers that can support an EC diagnosis include carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), estrogen receptors (ER), progesterone receptors (PR), cytokeratin 7 (CK-7), and pancytokeratins.[9][10]

Treatment / Management

Wide surgical excision with the goal of clear margins is the treatment of choice of EC.[4] Chemotherapy and radiation therapy have been used for metastatic lesions.[1] Because EC is an infrequent entity, no randomized control trials exist that examine the management options.

Differential Diagnosis

• Basal cell carcinoma (BCC): BCC is the most common malignancy of skin and approximately constitutes up to 80% of all skin cancers. BCC occurs more commonly in the sun-exposed skin. The most common presentation of BCC is in the form of a papule or a nodule. 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.
• Squamous cell carcinoma (SCC): SCC is the second most malignancy of skin. 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 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.
• Amelanotic melanoma: Amelanotic melanoma is a variant of melanoma that presents as white or reddish lesions. Similar to other common skin malignancies amelanotic melanoma is more common in sun-exposed skin. Similar to malignant melanoma, Amelanotic melanoma prognosis is determined by two important factors that include lesion thickness and lesion degree of invasion.
• Seborrheic keratosis: These are benign skin lesions affecting primarily adult patients. The lesion presents as a sharply demarcated pigmented greasy lesion that elevates above the surface of the skin. On microscopic examination, the lesion appears as an acanthotic proliferations of small cuboidal keratinocytes without any evidence of cytological atypia.
• Cutaneous lymphoma.
• Verruca vulgaris.
• Metastatic carcinoma: Skin metastases from breast, lung, or kidney carcinoma should be kept in the differential of eccrine carcinoma.

Staging

Eccrine carcinoma pathologically stages (pTNM) as follows:

Primary Tumor (pT)

• pTX: Primary tumor not assessable
• pT0: No evidence of primary tumor
• pTis: Carcinoma in situ
• pT1: Tumor 2 cm or less in the largest dimension
  • pT1a: Limited to the dermis or 2 mm or less in thickness
  • pT1b: Limited to the dermis and more than 2 mm in thickness, but not more than 6 mm in thickness
  • pT1c: Invading the subcutis and/or more than 6 mm in thickness
• pT2: Tumor greater than 2 cm but not more than 5 cm in its greatest dimension
  • pT2a: Limited to the dermis or 2 mm or less in thickness
  • pT2b: Limited to the dermis and more than 2 mm in thickness but not more than 6 mm in thickness
  • pT2c: Invading the subcutis and/or more than 6 mm in thickness
• pT3: Tumor over 5 cm in its greatest dimension
  • pT3a: Limited to the dermis or 2 mm or less in thickness
  • pT3b: Limited to the dermis and more than 2 mm in thickness, but not more than 6 mm in thickness
  • pT3c: Invading the subcutis and/or more than 6 mm in thickness
• pT4: Tumor invades the deep extradermal tissue (e.g., cartilage, skeletal muscle, bone)
  • pT4a: 6 mm or less in thickness
  • pT4b: More than 6 mm in thickness

Regional Lymph Nodes (pN)

• pNX: Regional lymph nodes not
• assessablepN0: No regional lymph node metastasis
• pN1: Regional lymph node metastasis

Distant Metastasis (pM)

• pMX: Presence of distant metastasis not
• assessablepM1: Distant metastasis

Prognosis

Metastatic disease shows a poor prognosis. The relative mortality rate is 80%, and the 10-year disease overall survival rate is 9%.[2]

Complications

Eccrine carcinoma complications include metastases and/or adverse effects related to surgical intervention.

Deterrence and Patient Education

Patients should receive education regarding the prognosis and the possible adverse side effects of surgical intervention before beginning treatment.

Enhancing Healthcare Team Outcomes

Eccrine carcinoma is an extremely rare cutaneous malignancy. The prognosis is overall favorable in localized early lesions, however an unfavorable prognosis in metastatic lesions.[1] Eccrine carcinoma needs an interprofessional management approach with a medical oncologist, surgeon, dermatologist, dermatopathologist, pharmacist, and oncology nurse all playing a role in the management of the condition and working collaboratively to bring about optimal patient treatment and outcomes. [Level 5]