Microcystic adnexal carcinoma

Microcystic adnexal carcinoma also called sclerosing sweat duct carcinoma, malignant syringoma, syringoid eccrine carcinoma, eccrine epithelioma, syringomatous carcinoma or sweat gland carcinoma with syringomatous features, is an uncommon, slow-growing, locally aggressive tumor of the eccrine sweat glands that typically extends far beyond the clinically evident lesion but has a low risk of regional or distant metastasis ¹. Sweat gland cancers, combining all types, are particularly rare, accounting for 0.005% of all malignant epithelial neoplasms ², with a total of ~350 cases currently described in the English literature. Clinically, microcystic adnexal carcinoma presents in the fourth to seventh decades of life, with no evident gender predilection although some literature lists a slight female predominance ³. However, microcystic adnexal carcinoma occasionally has occurred in children. It has been reported that the preferential location for the development of microcystic adnexal carcinoma is the head and neck region (85% of cases), demonstrating a preference for the periorbital skin and the centrofacial region ⁴.

Microcystic adnexal carcinoma or sclerosing sweat duct carcinoma is most common in Caucasians, but has been reported in African Americans, Spanish, Puerto Rican, Korean and Japanese patients ⁵. It also occurs in patients who previously received radiotherapy ⁶. Although extension to the muscle, vascular adventitia, perichondrium, periosteum and bone marrow has been reported, metastases are rare, occurring in approximately 2.1% of lesions ⁵. The estimated death rate is 0.2% ⁵.

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.

Microcystic adnexal carcinoma is commonly misdiagnosed about 27% of the time clinically and histologically, most commonly as desmoplastic trichoepithelioma ⁷, morpheaform basal cell carcinoma (BCC), or syringoma when superficial biopsy techniques are used ⁸. Less often, microcystic adnexal carcinoma is misdiagnosed as squamous cell carcinoma (SCC) because the superficial portion of microcystic adnexal carcinoma can have keratinaceous structures that resemble SCC ⁹.

Microcystic adnexal carcinoma is resistant to radiotherapy and chemotherapy, which may be predicted from its slow biological activity ¹⁰. The preferred treatment option is complete surgical excision; however, the true tumor-free margins are typically far beyond the intraoperative macroscopically established margins ¹¹. Mohs micrographic surgery may be regarded as the gold standard treatment option, with adjuvant radiotherapy and wide local excision offering comparable efficacy ¹². When performing adjuvant radiotherapy, a dose of >50 Gy should be administered with wide margins (3–5 cm), owing to the tendency of the lesion for perineural and deep invasion ¹³. Radiation may also be sought as treatment when standard surgical therapy may prove difficult and result in poor cosmetic outcome ¹⁴.

Figure 1. Microcystic adnexal carcinoma

Figure 2. Microcystic adnexal carcinoma

Footnote: Indurated plaque with a central crateriform depression and elevated pearly rolled out margins on the right side of upper lip.

[Source ¹⁵ ]

What are sweat glands?

There are two types of sweat glands: eccrine glands and apocrine glands. Eccrine and apocrine glands, hair follicles and sebaceous glands (which produce sebum) are often referred to as epidermal adnexal structures.

Sweat gland lesions generally have variable apocrine or eccrine differentiation. Traditionally these lesions have been categorized under either the apocrine or eccrine groups, but significant overlaps do exist.

Eccrine glands

Eccrine glands play an important role in the regulation of body temperature. They are distributed over the entire body skin but are highest in density on the palms and soles. Eccrine glands secrete a salty solution, which reaches the skin pores via an eccrine duct.

Eccrine sweat is a sterile electrolyte solution primarily containing sodium chloride, potassium and bicarbonate, with smaller quantities of various other components such as glucose and antimicrobial peptides. Sweat rate differs depending on the site on the body, the degree of thermal or physical stress, and between individuals. Under maximal stimulation, the body can produce 3 litres of eccrine sweat per hour.

Apocrine glands

In contrast, apocrine glands produce an oily fluid rich in triglycerides and fatty acids – subsequent colonization by anaerobic bacteria results in body odor.

Figure 3. Sweat glands

Microcystic adnexal carcinoma causes

The cause of microcystic adnexal carcinoma is not yet being fully understood, but it is believed to originate from pluripotent keratinocytes, which are capable of differentiation into hair follicles or sweat glands ¹⁶.

Risk factors for developing microcystic adnexal carcinoma

Risk factors have been identified for forming microcystic adnexal carcinoma:

• 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 ¹⁷. UV radiation is often implicated due to the fact that most lesions appear in sun-exposed areas and those with Fitzpatrick skin types 1 and 2.

Microcystic adnexal carcinoma has also been reported in younger individuals with a history of additional UV exposure, such as fighter pilots ¹⁸.

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

Microcystic adnexal carcinoma signs and symptoms

Microcystic adnexal carcinoma occurs as a slow growing, locally aggressive nodule, usually on the head or neck of an adult age 40 to 60 years ¹⁹. Typically, microcystic adnexal carcinoma appears as a solitary, smooth-surfaced, slow-growing, firm, non-ulcerated, asymptomatic skin-colored yellowish plaque, papule, nodule or cystic lesion ¹⁰. The lesion is most commonly located on the central face ⁵. Some studies have found microcystic adnexal carcinoma to be most often located on the left side of the face, possibly secondary to greater ultraviolet light exposure in cars ⁶. However, it has also been reported on the trunk ²⁰, extremities ²¹, genitals ²⁰, armpits ⁶ and scalp ²². Although usually asymptomatic, some lesions are associated with burning, pain, anesthesia or paresthesia, likely secondary to perineural invasion ²³.

It has been reported in the literature that certain microcystic adnexal carcinoma cases have presented with tumor histories as long as 17 and 27 years ²⁴. Notably, due to the asymptomatic presentation and extremely slow-growth of the tumors, all reported patients have been diagnosed at least 1 year after the initial appearance of the lesions.

Microcystic adnexal carcinoma 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.

Microcystic adnexal carcinoma diagnosis

Microcystic adnexal carcinoma often may be clinically indistinguishable from other skin-colored growths on the head and neck. microcystic adnexal carcinoma 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. The tumor largely lies within the deep dermis. A superficial biopsy can lead to an incorrect diagnosis. If microcystic adnexal carcinoma 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 microcystic adnexal carcinoma, 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 ²⁵.

Dermoscopy

Dermoscopy does not offer a definitive diagnosis of microcystic adnexal carcinoma. microcystic adnexal carcinoma 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 ²⁶. microcystic adnexal carcinoma can appear like a basal cell carcinoma due to the presence of arborizing vessels reported in case literature ²⁷.

Microcystic adnexal carcinoma histopathology

Microcystic adnexal carcinoma presents histologically as a deeply-infiltrative and poorly-circumscribed tumor, consisting of solid aggregates of tumor cells in the mid dermis, superficial keratinous cysts and elongated tubular structures in the deep aspect of the lesion. These cell nests are enveloped by dense, fibrous stroma ²⁸. Histologically, microcystic adnexal carcinoma can mimic infiltrative or 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 microcystic adnexal carcinoma from other tumors is a zone of separation between the epidermis and tumor. Additionally, the ductal structures distinguish microcystic adnexal carcinoma from desmoplastic trichoepithelioma and trichoadenoma.

Microcystic adnexal carcinoma is distinguished from morpheaform basal cell carcinoma and desmoplastic squamous cell carcinoma on the basis of ductal differentiation.

Immunohistochemistry

Immunohistochemistry (IHC) is utilized in the pathologic evaluation of microcystic adnexal carcinoma to help support the diagnosis. In particular, the carcinoembryonic antigen stain (CEA) is positive in approximately 50% of microcystic adnexal carcinoma cases. This helps distinguish microcystic adnexal carcinoma 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 microcystic adnexal carcinoma.

Microcystic adnexal carcinoma treatment

Mohs micrographic surgery is the treatment of choice, in order to obtain margins that are tumor-free with fewer procedures and therefore decrease the likelihood of recurrence ²⁹. In one study, the defect surface area after full extirpation following Mohs was a mean of 4 times that of the clinically apparent size, indicating that a margin cannot be safely predicted for conventional surgery; the recurrence rate was 1.98% per patient-year ²⁰. In another study of 44 cases treated by Mohs surgery, there was 1 case of recurrence in the 20 patients who completed the 5-year follow-up ³⁰.

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.

Local recurrence occurs in approximately 50% of cases treated with conventional excision, likely due to involvement of deep structures, such as skeletal muscle and perineural spaces ³¹. Although there has been a case report of success in treating a lower lip microcystic adnexal carcinoma with radiotherapy with 6 month follow-up, radiotherapy is not currently an indicated treatment, as it may induce conversion to a more clinically extensive and histologically aggressive tumor ³².

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

Microcystic adnexal carcinoma prognosis

The major prognostic concern for microcystic adnexal carcinoma is the recurrence of the tumor. The aggressive and locally invasive nature of microcystic adnexal carcinoma results in high recurrence rates ranging from 15–60% depending on the treatment modality, with lower rates of recurrence observed following Mohs micrographic surgery ³³. However, such data may be an overestimate, with misdiagnosis often occurring at the time of excision, and positive margins can occasionally be misread. Although extension to the muscle, vascular adventitia, perichondrium, periosteum and bone marrow has been reported, metastases are rare, occurring in approximately 2.1% of lesions ⁵. It has been reported that tumor recurrence may occur up to 30 years after the initial surgical excision ³⁴, highlighting the importance of regular, long-term follow-up.  According to the relevant literature, only one mortality has occurred as a result of microcystic adnexal carcinoma ³⁵. The estimated death rate is 0.2% ¹⁰.

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