Distant Metastatic Microcystic Adnexal Carcinoma

Abstract

Microcystic adnexal carcinoma (MAC) is a rare malignant neoplasm of ductal origin. MAC is a clinically aggressive, locally destructive tumor with a high rate of recurrence, but distant metastasis is rare. A 55-year-old male who had been taking immunosuppressants for 2 years after a liver transplantation due to hepatocellular carcinoma presented with a dermal nodule on the sole. He visited the clinic because the nodule, discovered 3 months ago, continued to increase in size. The histopathologic findings from the lesion were consistent with MAC. The patient underwent wide local excision and confirmed a histologically negative margin. After 11 months, the patient revisited with multiple skin nodules on the buttock, back, and right forearm that were distant from the primary tumor site. The lesions were histologically confirmed as MAC. We report a rare case of MAC with distant metastasis.

INTRODUCTION

Microcystic adnexal carcinoma (MAC) is an unusual and locally aggressive neoplasm of ductal origin with preponderance for local recurrence. Most often these neoplasms present as solitary flesh-colored indurated plaques on the upper lip¹. Possible triggers include UV exposure, immunosuppression, and radiotherapy had been suggested¹. A large primary tumor size is associated with the risk factor for recurrence¹. However, distant metastasis is extremely rare¹, and the associated risk factors are not known yet. The following presentation is a rare case of metastatic MAC with a review of literature reports of distant metastases.

CASE REPORT

A 55-year-old male presented with an asymptomatic dermal nodule on the right heel that was recognized 3 months ago. The patient had a medical history of high blood pressuere, diabetes, chronic kidney disease stage 3, non-ST-elevation myocardial infarction (NSTEMI) and liver transplantation due to hepatocellular carcinoma (HCC) 2 years ago and had been taking immunosuppressant, tacrolimus 2 mg daily. Patient did not report any other dermatologic history of photo damage, radiotherapy, melanoma and non-melanoma skin cancer. We received the patient’s consent form about publishing all photographic materials. Physical examination revealed a 9 mm-sized, hyperkeratotic dermal nodule on the right heel (Fig. 1A). A 4-mm punch biopsy revealed diffuse infiltration of ductal structures between hyalinized stroma (Fig. 1B). Immunohistochemical examination was positive for cytokeratin (CK) 7, epithelial membrane antigen (EMA), and negative for CK20 (Fig. 1C~E). As thyroid transcription factor 1 and glypican-3 were also negative, metastatic HCC and lung adenocarcinoma could be excluded. The nodule was diagnosed as MAC based on the clinical and histological findings. The patient underwent wide local excision with a 1-cm margin including the entire dermis. Histologically, malignant cells were not seen within 8 mm from the tissue edge and 2.6 mm from the deep margin, however, there was a perineural invasion.

Fig. 1. (A) A solitary 9-mm-sized, dermal nodule on the right heel. (B) A skin biopsy showed diffuse infiltration of tumor cells into the dermis and a nest of dysplastic epithelial cells in the desmoplastic stroma (H&E, ×100). Immunohistochemical staining that was (C) CK7 positive (×100), (D) EMA positive (×100), and (E) CK20 negative (×100).

After 11 months, the patient revisited our clinic and presented with multiple pale-pink nodules on the buttock, back and right forearm (Fig. 2A). A punch biopsy was performed on the right forearm and showed the identical findings as previous biopsy (Fig. 2B). Immunohistochemical examination was positive for CK7, EMA and negative for CK20 (Fig. 2C~E). Additional bone scan and Positron emission tomography-computed tomography (PET-CT) performed and revealed that multiple increased uptakes in both arms, buttock, and both lower legs, and multiple bones (Fig. 3). No lymph node metastasis was detected. The patient was referred to a tertiary hospital and died of heart failure 2 months later after single cycle of chemotherapy.

Fig. 2. (A) A pale-pink nodule on the right forearm. (B) A skin biopsy showed diffuse infiltration of tumor cells into the dermis and a nest of dysplastic epithelial cells in the desmoplastic stroma (H&E, ×100). Immunohistochemical staining that was (C) CK7 positive (×100), (D) EMA positive (×100), and (E) CK20 negative (×100).

Fig. 3. (A) Additional bone scan and (B) positron emission tomography-computed tomography (PET-CT) performed and revealed that multiple increased uptakes in both arms, buttock, and both lower legs, and multiple bones (arrows).

DISCUSSION

MAC is an uncommon cutaneous malignant neoplasm that is associated with significant morbidity in light of its propensity for local invasion². Although the pathophysiology is unclear, possible causes include ultraviolet radiation, prior radiation therapy, and immunocompromised states¹. Histopathologically, it is characterized by diffuse infiltrating syringomatous ductal differentiation. Differential diagnoses include desmoplastic trichoepithelioma (DTE) and morpheaform basal cell carcinoma (mBCC). Immunostaining is useful to differentiate² MAC from both disease. Carcinoembryonic antigen, EMA, CK20 is useful to rule out DTE and Ber-ep4 is useful to rule out mBCC¹.

MAC is locally invasive tumor that frequently extends into deep tissues including subcutaneous fat, muscle and bone, even beyond the clinical margin². However, despite of the locally invasive nature, distant metastasis is very rare. Only five cases of metastasis have been reported to date²,³,⁴,⁵,⁶. Of these, the location of the primary tumor was the face in three cases, the scalp in one case and the hand in one case. The time to diagnosis of distant metastasis was more than 20 years for two cases, 5 to 10 years for one case and less than 5 years for two cases. For the cases of distant metastasis that were diagnosed within 5 years, one was in an immunocompromised patient, and the other was in a patient with a primary tumor in the extremity (Table 1).

Table 1. Distant metastatic microcystic adnexal carcinoma: a summary of cases.

No.	Authors, year	Age (yr)	Sex	Underlying disease	Primary site	Primary treatment	Time to metastasis/site	Prognosis
1	Bier-Laning et al.2 (1995)	46	F	None	Right upper lip & Medial cheek	Excision and adjuvant radiotherapy	22 years/contralateral suprahyoid neck lymph node	Repeated local recurrence for 10 years despite excision, radiotherapy, and chemotherapy
2	Carroll et al.3 (2000)	86	M	CLL	Scalp	Mohs micrographic surgery	5 months/scalp, distant to primary site	Metastatic lesions were treated with radiotherapy and surgery
								Expired after 7 months due to CLL aggravation
3	Ohta et al.4 (2004)	53	F	None	Left eyebrow	Partial excision and palliative therapies	20 years/bone (left clavicle, bilateral 12th rib) Liver	Metastasis confirmed at autopsy
4	Gabillot-Carré et al.5 (2006)	62	M	None	Nasolabial fold	Excision	8 years/both upper lobes of lung	A lobectomy was performed on both lobe nodules
								Alive with slowly progressive local recurrence for 67 months
5	Chen and Laber6 (2017)	68	M	None	Left thumb	Excision and adjuvant radiotherapy	3 years/liver, spleen, lung	The disease progressed even after chemotherapy (carboplatin +paclitaxel) for 9 months

CLL: chronic lymphocytic leukemia, F: female, M: male.

In this case, the primary tumor was in the right sole and the patient had a history of taking immunosuppressive agent. It is known that non-melanoma skin cancers in organ transplant patients show an increased risk of incidence and aggressive subclinical extension⁷. It is also known that cutaneous adnexal tumor is more likely to occur in organ transplant patients⁸. In cutaneous adnexal tumor, poor prognostic factors for overall survival include increasing age, node and distant metastasis, high tumor stage and untreated cases⁹. The study conducted on adnexal tumors showing eccrine differentiation reported that the higher the stage and poorer tumor differentiation, the poorer overall survival¹⁰. MAC reports that large tumor size increases secondary morbidity, but there is no report on factors related to tumor aggressiveness¹. Well-designed cohort or prospective studies are needed to clarify the risk factors for MAC aggressiveness.