Microcystic Adnexal Carcinoma

Etiology

Risk factors have been identified for forming MAC:

• Ultraviolet (UV) radiation
• Previous radiation therapy
• Immunosuppressive medications

The estimate for the link to therapeutic radiation ranges from 19% to 50%, with an average latent period of 30 to 40 years. UV radiation is often implicated because most lesions appear in sun-exposed areas and those with Fitzpatrick skin types I and II.

Microcystic adnexal carcinoma has also been reported in younger individuals with a history of additional UV exposure, such as fighter pilots.[2]

The effect of immunosuppression on the risk for the development of MAC is unclear at this time, although immunosuppression increases the risk of basal cell carcinoma and squamous cell carcinoma.

Epidemiology

MAC tends to occur in adults 55 to 60 years old. However, it occasionally has occurred in children. Microcystic adnexal carcinoma arises equally in males and females although some literature lists a slight female predominance.[3]

Pathophysiology

Microcystic adnexal carcinoma often grows slowly and will present as a white to pink plaque located on the face. Often, it has been overlooked or ignored. Often it is confused with a basal cell carcinoma clinically. In such an instance, a shave biopsy is usually performed. However, in the case of microcystic adnexal carcinoma, the pathology lies deeper than a superficial shave biopsy will show. Thus, making the diagnosis more difficult. If suspected, a punch biopsy should be performed.

Histopathology

Histologically, MAC can mimic infiltrative/morpheaform basal cell carcinoma, desmoplastic squamous cell carcinoma, desmoplastic trichoepithelioma, trichoadenoma, and syringoma. 

Histopathological examination reveals small basaloid cells/keratocysts on the top, hence the term “microcystic.” This is a key feature. On higher power, one can see cords and strands of basaloid epitheloid cells displaying ductal lumina that invade the dermis and subdermis. There is also fibrotic stroma. A key feature in distinguishing MAC from other tumors is a zone of separation between the epidermis and tumor. Additionally, the ductal structures distinguish MAC from desmoplastic trichoepithelioma and trichoadenoma.

MAC is distinguished from morpheaform basal cell carcinoma and desmoplastic squamous cell carcinoma based on ductal differentiation.

Immunohistochemistry

• Immunohistochemistry (IHC) is utilized in the pathologic evaluation of MAC to help support the diagnosis. In particular, the carcinoembryonic antigen stain (CEA) is positive in approximately 50% of MAC cases. This helps distinguish MAC from basal cell carcinoma and squamous cell carcinoma, where CEA is negative.

Stains

• Hematoxylin and eosin (H&E) stain is the standard stain used in the diagnosis of MAC.

History and Physical

Microcystic adnexal carcinoma is a solitary white to pink plaque located on the face or trunk. In the case of early tumors, the appearance may be slightly elevated; however, a more nodular appearance tends to develop with time.

Evaluation

MAC often may be clinically indistinguishable from other skin-colored growths on the head and neck. MAC may have perineural spread where patients can complain of numbness, tingling, pain, burning, and itching sensations. The key to

diagnosis is taking an appropriate pathology specimen is needed, and the key to diagnosis. The tumor largely lies within the deep dermis. A superficial biopsy can lead to an incorrect diagnosis. If MAC is suspected, avoid a superficial shave biopsy.

An incisional biopsy is recommended in the evaluation. However, punch biopsies and excisional biopsies are options in evaluation.

Full Skin Examination

• If a biopsy results in a diagnosis of MAC, a full-body skin examination should take place.

Lymph Nodes

• Lymph node examination should be performed to assess for regional metastases, albeit rare.
• Fine needle aspiration (FNA) or excisional biopsy of enlarged lymph nodes should be performed if detected on examination.

Imaging

Consider the need for imaging (CT or MRI) or fat-suppression MRI protocol for perineural invasion or intraorbital tumors.[4]

Dermoscopy

Dermoscopy does not offer a definitive diagnosis of MAC. MAC is a rare tumor, so dermoscopic findings are limited to case reports with the most characteristic finding appears to be the presence of whitish clods of variable size. These whitish clods likely representing keratinous cyst.[5][6][7] MAC can appear like a basal cell carcinoma due to the presence of arborizing vessels reported in case literature.[8]

Treatment / Management

MAC is managed surgically by simple excision or Mohs micrographic surgery (MMS). Complication rates between MMS and simple excision are similar. When utilizing MMS, clear margins were obtained in fewer procedures and resulted in fewer office visits.[9](B2)

In the event that Mohs micrographic surgery is not an option due to lack of procedure availability or tumor extent, intraoperative frozen sections may be useful for guiding conventional surgical excision.

Patients should be followed every six to twelve months following diagnosis and management for full-body skin examination and lymph node examination.

Differential Diagnosis

MAC presents often on the face as a papule or plaque. The differential can be large. However, the differential diagnosis where MAC must be distinguished from is morpheaform basal cell carcinoma, desmoplastic squamous cell carcinoma, desmoplastic trichoepithelioma, trichoadenoma, and syringoma.[3]

Surgical Oncology

• Sentinel lymph node biopsy (SLNB) is not recommended for the staging of MAC as per the current evidence-based clinical practice guidelines.[4]
• Evidence is lacking that supports neck dissection for a positive lymph node at presentation.
• Node positive and metastatic disease should be treated surgically as per the local disease.[2]

Radiation Oncology

The role of radiation therapy for microcystic adnexal carcinoma remains unclear. Monotherapy with radiotherapy is not recommended. According to the latest evidence-based clinical practice guidelines for MAC, adjuvant radiotherapy can be considered for MAC when there is peripheral nerve involvement, when margins and unable to be cleared surgically, or when there is a tumor present at the margins. Although, there have been reports of chemoradiation with carboplatin/paclitaxel combination used in a patient refusing surgical management that remained tumor-free for six years.[10]

Prophylactic radiotherapy of the sentinel node base is not supported by current evidence.[4]

Prognosis

The major prognostic concern for MAC is the recurrence of the tumor. Recurrence is generally seen within two to three years; however, it may occur even decades later.[11] MAC is a locally aggressive tumor whereas metastases are generally rare. Death may result from the invasion of vital structures.

Complications

Complications of untreated tumors are locally aggressive invasion. Depending on location, complications can result from the invasion of vital structures. In some instances, death has resulted.