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Year : 2022  |  Volume : 65  |  Issue : 2  |  Page : 459-461
Primary cutaneous adenoid cystic carcinoma – An onerous task for clinicians and pathologists

1 Department of Pathoogy, Navodaya Medical College, Raichur, Karnataka, India
2 Department of Pathoogy, Kannur Medical College, Kannur, Kerala, India

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Date of Submission23-Sep-2020
Date of Decision14-Feb-2021
Date of Acceptance06-Oct-2021
Date of Web Publication14-Apr-2022


Adenoid cystic carcinoma (ACC) is an uncommon malignant neoplasm usually confined to the salivary glands, lungs, and breasts. Primary cutaneous adenoid cystic carcinoma (PCACC) is an extremely rare entity with solitary cases reported at sites away from the scalp and chest. Hence, one must follow the multidisciplinary approach to exclude any primary ACC elsewhere in the body. We report a rare case of PCACC arising from the skin of the left lower limb in a 55-year-old woman with a history of recurrent swelling, clinically diagnosed as a metastatic tumor.

Keywords: Adenoid cystic carcinoma, primary, skin

How to cite this article:
Yaranal PJ, Bithun B K, Anand A S. Primary cutaneous adenoid cystic carcinoma – An onerous task for clinicians and pathologists. Indian J Pathol Microbiol 2022;65:459-61

How to cite this URL:
Yaranal PJ, Bithun B K, Anand A S. Primary cutaneous adenoid cystic carcinoma – An onerous task for clinicians and pathologists. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Dec 4];65:459-61. Available from:

   Introduction Top

Adenoid cystic carcinoma (ACC), a well-recognized malignant neoplasm, is usually confined to the minor and major salivary glands, where it carries a poor prognosis. It can occasionally occur as a primary neoplasm at the extra salivary gland tissue too. Commonly noted extra salivary primary ACC is in the breasts, lungs, vulva, and skin. Primary adenoid cystic carcinoma (PACC) of the skin is extremely rare and they are locally aggressive mimicking their salivary counterpart with a recurrence rate of 51%.[1] Baggio (1975) was the first to describe it,[2] and less than 70 cases of PCACC cases have been reported in English literature.[3] Seab and Graham reported the first case of PCACC on the thigh,[1] and the present case is assumed to have the credential of the second case report of PCACC arising on the lower extremity. We report a rare case of PACC involving the skin of the left lower limb.

   Case Report Top

Clinical history

A 55-year-old woman was referred from the surgical outpatient department with a small recurrent swelling on the left leg of a 1-year duration. Clinically, she presented with a single firm to a hard and tender nodule of 1.5 × 1.0 cm over the medial malleolus of the left leg and was subjected to Fine needle aspiration cytology (FNAC). Past surgical history was significant with similar swelling at the same location 3 years ago, reported as metastatic adenocarcinoma of the skin and advised to look for the primary tumor. Subsequently, when investigated by ultrasonography (USG), mammography, whole-body positron emission tomography–computed tomography (PET–CT) scans, and bone scintigraphy, the primary tumor was not localized.

Cytological findings

Smears showed moderate cellularity with neoplastic cells arranged in variable-sized three-dimensional clusters and singles. The cells were round to oval showing moderate eosinophilic cytoplasm, pleomorphic nuclei with increased nucleocytoplasmic ratio and prominent nucleoli, and a background with cell debris. The differential diagnosis of, clear cell sarcoma, epithelioid synovial sarcoma, and amelanotic melanoma were considered and further advised for excision biopsy [Figure 1]a and [Figure 1]b.
Figure 1: (a). Cellular aspirate showing neoplastic cells arranged in clusters (PAP ×100). (b). Variable-sized, three-dimensional clusters and singles with hyaline globules (PAP ×400). (c). Skin ellipse with a central nodule measuring 1.5 × 1 × 1 cm. The cut section of the nodule is gray–white

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Gross pathology

A wide excision biopsy specimen was received measuring 3.2 × 2 × 1.2 cm with an attached elliptical piece of skin on one side. The cut section showed a gray–white nodule measuring 1.5 cm × 1 cm with a depth of 0.9 cm; the deep resected margin was 0.3 cm away from the tumor [Figure 1]c.

Histopathological findings

Sections showed an infiltrating tumor composed of islands of basaloid cells in cords, nests, cribriform, and tubular arrangements localized in the reticular dermis and subcutis with no involvement of the epidermis. Tumor cells were mildly pleomorphic with moderate eosinophilic cytoplasm, vesicular nuclei, and occasional prominent nucleoli. Few hyaline globules were noted, and the tumor was embedded in abundant fibromyxoid stroma. Resected margins were free of tumor, and diagnosis of malignant adnexal tumor, suggestive of ACC was offered [Figure 2]a and [Figure 2]b.
Figure 2: (a) Skin with dermal tumor showing a predominant cribriform pattern (H&E ×200). (b). Nests of basaloid cells with cribriform and tubular patterns and abundant mucin in cysts and between cells (H&E ×400). (c). Immunohistochemical staining showing strong expression of EMA in ductal component and (d) S100 in myoepithelial component (×200)

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A retrospective review of FNAC smears revealed an occasional gland-like arrangement of cells with a few hyaline globules [Figure 1]a and [Figure 1]b. One of the FNAC smears was destained and forwarded to Periodic acid–Schiff (PAS) stain, which showed positivity for hyaline globules. On further evaluation by immunohistochemistry, Epiththelial membrane antigen (EMA) and vimentin highlighted the ductal component of the tumor, [Figure 2]c and the myoepithelial component was positive for S100 and cytokeratin [Figure 2]d. The tumor was Negative for thyroid transcription factor-1 (TTF-1), carcinoembryonic antigen (CEA) and thyroglobulin.

Finally, the case was reported as PCACC of the left lower limb. No local recurrence or distant metastasis was seen a year after the initial diagnosis.

   Discussion Top

Primary cutaneous adenoid cystic carcinoma (PCACC) is an extremely rare entity, but very few solitary cases are reported at sites away from the scalp and chest,[4] where the scalp accounts for 41%,[5] whereas it is sparsely distributed in other locations such as the chest wall, abdomen, back, eyelids, and perineum.

It usually affects the middle-aged and elderly population with a female preponderance.[6] PCACC presents clinically as a firm, poorly circumscribed, slow-growing intradermal or subcutaneous nodule with an average tumor size of 3.5 cm.[5]

Morphologically, the cutaneous variant of ACC is indistinguishable from ACC occurring at other sites. PCACC characteristically is a mid-to-deep reticular dermal tumor consisting of basophilic cells in adenoid or cribriform pattern with a true lumina surrounded by modified myoepithelial cells and prominent basement membrane material.[5]

The histomorphologic differential diagnosis of PCACC includes metastatic adenocarcinoma, cylindroma, adenoid basal cell carcinoma, mucinous apocrine carcinoma, apocrine mixed tumor of the skin, and cutaneous metastasis of ACC. It is mandatory to exclude all these histological mimics before arriving at this particular diagnosis.[5]

ACC is currently regarded to have an apocrine histogenesis[6] because of its immunohistochemical staining properties. In addition to cytokeratin and S100 protein positivity of cutaneous ACC, a few tumors were CEA positive (ductal epithelial differentiation), whereas others were SMA positive (myoepithelial differentiation).[2]

PCACC is strongly EMA positive; however, CEA positivity is variable, whereas extracutaneous ACC is consistently CEA positive. S-100 and cytokeratin positivity is a common feature of both PCACC and extracutaneous ACC, whereas adenoid basal cell carcinoma does not express EMA.[5]

In general, the prognosis of PCACC is better and they exceptionally metastasize, compared to those occurring at other sites.[2],[7] Metastatic disease to the skin is a much more common entity and has a grave prognosis. Due to its nature, the pathologist needs to exclude a primary tumor elsewhere in all cutaneous ACCs. Because the morphological features of PCACC are indistinguishable from that of a metastatic ACC,[2] it becomes all the more challenging to arrive at a diagnosis of PCACC without ancillary testing and a detailed workup of the patient.

To conclude, the definitive diagnosis of PCACC primarily relies on histomorphology with additional advantages using special stains such as PAS or Alcian blue and a carefully chosen immunohistochemical panel. Exclusion of the metastatic malignancy is mandatory before considering the diagnosis of PCACC. According to the literature, as there are very small numbers of cases documented, there is a vast scope for further research on PCACC. Hence, this must be followed by a multidisciplinary approach to exclude any primary ACC elsewhere in the body.[2],[8]

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.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Seab JA, Graham JH. Primary cutaneous adenoid cystic carcinoma. J Am Acad Dermatol 1987;17:113-8.  Back to cited text no. 1
Ramakrishnan R, Chaudhry IH, Ramdial P, Lazar AJ, McMenamin ME, Kazakov D, et al. Primary cutaneous adenoid cystic carcinoma: A clinicopathologic and immunohistochemical study of 27 cases. Am J Surg Pathol 2013;37:1603-11.  Back to cited text no. 2
Mauritz A, Vandendriessche A, Thiessen F, Tondu T, Wetzels K, Mangodt E, et al. Primary cutaneous adenoid cystic carcinoma of the lower limb: Rare tumor in a rare location. A case report and brief review of literature. Ann Case Report 2020;14:567.  Back to cited text no. 3
Koh BK, Choi JM, Yi JY, Park CJ, Lee HW, Kang SH. Recurrent primary cutaneous adenoid cystic carcinoma of the scrotum. Int J Dermatol 2001;40:724-5.  Back to cited text no. 4
Naylor E, Sarkar P, Perlis CS, Giri D, Gnepp DR, Robinson BL. Primary cutaneous adenoid cystic carcinoma. J Am Acad Dermatol 2008;58:636-41.  Back to cited text no. 5
Kato N, Yasukawa K, Onozuka T. Primary cutaneous adenoid cystic carcinoma with lymph node metastasis. Am J Dermatopathol 1998;20:571-7.  Back to cited text no. 6
Singh A, Ramesh V. Primary cutaneous adenoid cystic carcinoma with distant metastasis: A case report and brief literature review. Ind J Dermatol Venereol Leprol 2010;76:176-9.  Back to cited text no. 7
Meyrick Thomas RH, Lowe DG, Munro DD. Primary adenoid cystic carcinoma of the skin. Clin Exp Dermatol 1987;12:378-80.  Back to cited text no. 8

Correspondence Address:
Parasappa Joteppa Yaranal
Professor of Pathoogy, Navodaya Medical College, Raichur-584103, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_1162_20

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