A Case Report of a Primary Cutaneous Adenoid Carcinoma: A Diagnostic and Management Challenge

Adenoid cystic carcinoma (ACC) is a slow growing, usually asymptomatic neoplasm most commonly associated with secretory glands. Rarely is it observed as a primary tumor on the skin. It is unclear whether PCACC is of eccrine or apocrine origin. Salivary gland ACC rarely metastasizes to skin. However, ACC is also observed in the lungs, breasts, prostate and cervix and identification of cutaneous ACC should prompt investigations for metastasis or direct extension from salivary glands adjacent to the skin. Further, the median age for developing PCACC is 61 years old with equal disease incidence in men and women. Primary neoplastic sites include the head and neck (46%), followed by upper limbs (17%), trunk (15%) and lower limbs (13%). We report a case of PCACC that presents both as a diagnostic and management challenge. A 52 year old female presented to an outpatient dermatology clinic with an asymptomatic 5 mm skin colored, subcutaneous papule on the left mid back resembling a cyst. Given the clinical resemblance to a cystic lesion, it was treated with intralesional triamcinolone. Despite treatment, the lesion persisted and a biopsy was performed. Histologic examination showed a dermal nodular proliferation of basaloid islands and cords separated by spaces with an amorphous PAS material. Initial pathology was interpreted as a benign sweat duct tumor, demonstrating the diagnostic challenges with these lesions. Cognizant that malignant sweat gland tumors can be misread as benign lesions, a second opinion from a more experienced dermatopathologist was sought. On second opinion the diagnosis was of a malignant, low-grade, sweat duct tumor. Staining of areas of ductal ABSTRACT

Adenoid cystic carcinoma (ACC) is a slow growing, usually asymptomatic neoplasm most commonly associated with secretory glands. Rarely is it observed as a primary tumor on the skin. 1 It is unclear whether PCACC is of eccrine or apocrine origin. 2 Salivary gland ACC rarely metastasizes to skin. 3 However, ACC is also observed in the lungs, breasts, prostate and cervix and identification of cutaneous ACC should prompt investigations for metastasis or direct extension from salivary glands adjacent to the skin. 1 Further, the median age for developing PCACC is 61 years old with equal disease incidence in men and women. Primary neoplastic sites include the head and neck (46%), followed by upper limbs (17%), trunk (15%) and lower limbs (13%). 1,4 We report a case of PCACC that presents both as a diagnostic and management challenge.
A 52 year old female presented to an outpatient dermatology clinic with an asymptomatic 5 mm skin colored, subcutaneous papule on the left mid back resembling a cyst. Given the clinical resemblance to a cystic lesion, it was treated with intralesional triamcinolone. Despite treatment, the lesion persisted and a biopsy was performed. Histologic examination showed a dermal nodular proliferation of basaloid islands and cords separated by spaces with an amorphous PAS + material. Initial pathology was interpreted as a benign sweat duct tumor, demonstrating the diagnostic challenges with these lesions. Cognizant that malignant sweat gland tumors can be misread as benign lesions, a second opinion from a more experienced dermatopathologist was sought. On second opinion the diagnosis was of a malignant, low-grade, sweat duct tumor. Staining of areas of ductal differentiation showed CEA + , EMA + , S100+ and LMWCK + and c-Kit + (cd117) favoring the diagnosis of an ACC (Figure 1). The lesion was excised by wide local excision with 1.0 cm tumor free margins. A complete lymph node examination did not show any lymphadenopathy. Whole body PET-CT did not show metastasis suggesting local, regional disease.
Management of ACC remains a challenge since there is a high incidence of recurrence especially if there is perineural invasion. 5 Recurrence following surgical resection is around 44% with an average follow-up time of 58 months. 3,5 There is no consensus on the optimal treatment of PCACC. Surgical excision with adjuvant radiotherapy is routinely used for PCACC with skin-limited disease, although comparative studies have not conclusively demonstrated that adjuvant radiotherapy is superior to surgery alone. 6 Reported surgical modalities include local excisions, wide local excision (WLE) with 1.0 -2.0 cm safety margins and Mohs surgery. 2,5,7 Perineural invasion and local recurrence has been reported in 76% and 44%, respectively with traditional surgical excision. 5  Staging of PCACC should include routine lymph node examination with whole body imaging to assess for extracutaneous involvement. Lymph node dissection is suggested for nodal involvement 5 . Whole body imaging should include the head and neck since primary ACC accounts for 10% of salivary glands neoplasms. The most common areas for metastasis include the lungs, bone and liver. Since primary ACC can arise from breast and in the DISCUSSION genitourinary tract, an age appropriate mammogram, PAP smear and/or prostate examination should be included in the workup. 2 Chemotherapy is first line for advanced, metastatic ACC, albeit this is not standardized. 8 Classical chemotherapy agents including cisplatin, 5-fluorouracil, or a combination of cisplatin, doxorubicin and cyclophosphamide are utilized for metastatic disease. Several studies have shown that drugs targeting epidermal growth factor receptor or the downstream tyrosine kinases has shown some promise in treating advanced ACC in a cohort of patients. 8 More molecular, genetic and clinical studies are needed to identify therapeutic agents specifically targeting ACC.
There are no standard guidelines for followup of patients with PCACC. PCACC follows an indolent course and the reported time to recurrence following surgical excision ranges from 1 month to 35 years. 3 A review of fifty cases in the literature showed that on average the cases recurred within 58 months. 3 Follow-up frequency may also vary depending on the presence of any metastatic disease. Therefore, there is insufficient evidence to support any definitive recommendations for follow-up and this should be done on a case-by-case basis.
PCACC can be diagnostically challenging owing to its indolent growth and its ability to mimic benign entities. Although there is no consensus regarding management of PCACC, we suggest WLE of at least 1.0 cm margins, full lymph node examination and imaging to elucidate the etiology. Routine follow-up with imaging is suggested given the high incidence of recurrence.