Unsuspecting Plaque on the Forearm: A Diagnostic Challenge

Abstract

Microcystic adnexal carcinoma (MAC) is a rare, slow-growing, locally aggressive malignant, and recurring appendageal tumor. Prolonged UV exposure, immunosuppression, and radiotherapy are a few frequently associated risk factors. MAC classically presents as an asymptomatic skin coloured plaque on the face. The key to diagnosis is a deep-sectioned biopsy. Surgical modalities are the first line of treatment.

Introduction

Appendageal tumors are neoplasms that develop from the pilosebaceous, apocrine, or eccrine sweat gland apparatus. Because of the abundance of these structures, they are most commonly found in the head and neck region. Clinical diagnosis is typically challenging because most of them appear as asymptomatic papules or nodules. The classical anatomical site, distribution, and number of lesions, provide vital clues, but histology is the gold standard in confirming the diagnosis. The majority of these tumors are benign. We discuss a case of a rare appendageal tumor found at an unusual site.[1]

Case Report

A 45 year old male patient, a chef by occupation, with no comorbidities presented with a single raised asymptomatic lesion over the right forearm for 20 years. The lesion was initially pea sized which gradually increased to the current size. There was no history of similar complaints in past or in the family. Examination revealed a solitary, well-defined, firm to hard, non-tender, indurated plaque of 5cm diameter over the right forearm. The lesion was freely mobile over the underlying structures with a positive finger insinuation sign [Figure 1]. There was no local rise in temperature and no regional lymphadenopathy. Basidiobolomycosis, sarcoidosis, and leishmaniasis were considered as differential diagnoses, and an incisional biopsy was done and sent for histopathological examination. The pathologist’s initial report was suggestive of syringoma, however, this did not correlate with the clinical presentation, further revaluation of the slide was done and a final diagnosis of MAC was concluded. Histopathology showed a dermal neoplasm arranged in ducts-like structures and cords. These cells were small and monomorphic with finely granular chromatin, prominent nucleoli, and moderate eosinophilic cytoplasm. Small keratin cysts were noted [Figures 2-4]. Immunohistochemistry showed S100 positivity [Figure 5].

Figure 1.

A solitary, well-defined, firm to hard plaque of 5cm diameter over right forearm with a positive finger insinuation sign

Figure 2.

Dermal tumor with neoplastic epithelial tadpole-shaped ducts with eosinophilic secretions giving a ‘paisley tie appearance’ (H and E Scanner view)

Figure 4.

Neoplastic epithelial tadpole-shaped ducts (H&E, 400x)

Figure 5.

Immunohistochemistry showing S100 positivity

Figure 3.

Keratin cyst in upper dermis (H&E, 400x)

Discussion

Microcystic adnexal carcinoma (MAC) is a rare, slow growing, locally aggressive malignant and recurring appendageal tumor, first described in 1982 by Goldstein et al.[2] One thousand nine hundred sixty eight cases of MAC have been reported in literature.[3] In a study done in the United States on 708 MAC cases, 48 were present on upper limbs.[4] It is also referred to as sweat gland carcinoma with syringomatous features, malignant syringoma, sclerosing sweat duct carcinoma, and syringomatous carcinoma. It is commonly seen in Caucasians. Prolonged UV exposure, immunosuppression, and radiotherapy are a few frequently associated risk factors. MAC classically presents as an asymptomatic skin coloured plaque on the face but is commonly ignored.[5,6,7] The lesions can also be seen in axilla, extremities, trunk and groin but it is very rare.[8] There may be peri-neural involvement which presents as numbness, tingling, itching, or pain.[5,6,7]

The key to diagnosis is a deep-sectioned biopsy. Histopathology will show a deeply infiltrative, poorly circumscribed, asymmetric tumor. It has two components—the upper dermis, which usually contains keratin horn cysts and nests of basaloid cells with follicular differentiation, and the deeper dermis which contains neoplastic epithelial tadpole-shaped ducts with eosinophilic secretions giving a paisley tie appearance. These ductal structures are surrounded by a deep pink sclerotic stroma which is often fibrotic and commonly shows perineural and intramuscular invasion. Misdiagnosis is common due to inadequate sampling and little cytologic atypia.[6,9]

Several immunohistochemical stains have been utilized to differentiate MAC from infiltrative BCC, desmoplastic trichoepithelioma, and other mimics. Unfortunately, MAC does not have a distinct immunohistochemical profile, and inconsistent results have been observed. The carcinoembryonic antigen stain, which is positive in 50% of all MACs, is very useful in distinguishing MAC from BCC and SCC. In addition, some investigations have found that Ber-EP4 is negative in MAC but positive in BCC. Over the past decade, many stains such as Ki67, AE14, CK7, CK15, CK17, CK19, CK20, and PHLDA1 have been studied to differentiate MAC from desmoplastic trichoepitheliomas and infiltrative/morpheaform BCC. However, none of them have proven to be completely reliable.[8,9]

Differential diagnosis

Syringoma, trichoadenoma, desmoplastic trichoepithelioma, osteoma cutis, squamous cell carcinoma, morpheaform basal cell carcinoma, and metastatic breast carcinoma. While both syringomas and MAC have ductal structures, syringomas are distinguished due to their lack of prominent horn cyst formation. Desmoplastic trichoepithelioma and trichoadenoma lack ductal structures but may have horn cysts like MAC.[5,9,10] Adenoid cystic carcinoma (ACC) is also a close differential diagnosis to MAC. It is an epithelial tumor that usually originates from the oral and maxillofacial salivary glands. ACC has a slow growth and is locally aggressive similar to MAC. ACC has a higher prevalence of perineural invasion (76%) making pain a common symptom. Histopathological examination shows basaloid cells and myoepithelial cells in nests with a cribriform (Swiss cheese) pattern whereas microcystic adnexal carcinoma shows a paisley tie appearance. The nests often have a central, hyaline-like zone surrounded by a more cellular periphery which is not seen in our case. There are no specific IHC markers to differentiate between the two.[11,12]

Table 1 depicts the difference between histological mimickers.[13,14]

Table 1.

Histopathological differential diagnosis of MAC

Characteristics	MAC	Syringoma	Desmoplastic trichoepithelioma	Morpheaform Basal cell carcinoma
Stroma	Red, sclerotic	Red, sclerotic	Red, sclerotic	Red, sclerotic, may have mucin
Paisley tie pattern	Present	Present	Present	Superficially present sometimes
Horn cyst	Commonly seen	Occasionally seen	Commonly seen	Occasionally seen
Calcification	Rare	Rare	Common	Rare
Perineural invasion	Present	No	No	Sometimes present
Central dell	No	No	Yes	No
Deeply invasive	Yes	No	No	Can be
Immunohistochemistry	No specific marker CK15, CK19 - Positive BerEP 4 – Negative	CEA- Positive CK20 –negative	CK20, BerEP4, PHLDA1, CK15 – Positive	BerEP4, AR – Positive PHLDA1, CK15 , CK20 - Negative

Management

Surgical modalities are the first line of treatment. Mohs micrographic surgery or complete circumferential peripheral and deep margin assessment is recommended. Wide local excision can be performed in resource-poor settings, with 2 cm margins and deep margins up to the fascia. Radiotherapy is preferred if any contraindications to surgery. A fractionated dose of greater than 60 Gy at 2 Gy per fraction is given.

Chemotherapy regimens, with platinum-based agents like taxane or with 5-fluorouracil, have been tried. Cetuximab in combination with cisplatin and paclitaxel or sorafenib monotherapy, has been reported for metastatic disease which is very rare. The majority of irradiated tumors have recurred, making this malignancy largely radioresistant. The literature is limited; however, it shows an overall high MAC recurrence rate of 47% following standard excisional surgery. The margins reported for primary tumor excision ranged from a few millimeters to large resections with 3- to 5-cm margins. The majority of recurrences have occurred within a median of 3 years, but MAC reoccurring as late as 30 years following treatment has been documented, underlining the necessity for continuous follow-up. Perineural invasion is linked to recurrence. Following treatment recurrence rates vary between 40% and 60% for wide local excision and 0–12% for Mohs micrographic surgery.

A regular follow-up is imperative since the rate of recurrence is high. Patients should also be taught about self-examination and the need for follow-up annually for a minimum period of 5 years should be stressed upon, where a complete skin and lymph node examination may need to be done.[3,15,16]

Conclusion

We would like to highlight the atypical site of presentation of microcystic adnexal carcinoma which is typically seen on the face. Therefore, solitary asymptomatic lesions can have an array of differential diagnosis and appendageal tumors though rare may be considered as one of them. Histopathological examination can clinch the diagnosis in these cases. Also early diagnosis and prompt treatment is necessary due to the risk of metastasis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.