Sclerosing Microcystic Adenocarcinoma Presenting as a Chronic Floor-of-Mouth Mass

Significance Statement

Sclerosing microcystic adenocarcinoma (SMA) is an exceedingly rare, locally aggressive, yet biologically indolent salivary gland carcinoma that was formally recognized as a distinct entity only in the 2022 WHO classification. Its rarity, historically inconsistent terminology, and striking histologic overlap with other entities pose significant diagnostic challenges, particularly in limited biopsy material. Heightened awareness among clinicians and pathologists is therefore crucial for accurate diagnosis and optimal patient management.

A 50-year-old man with chronic hepatitis B and a history of undifferentiated intrahepatic cholangiocarcinoma, status post left hepatic lobectomy (pT1N0Mx) 16 years earlier, presented with right-sided throat pain persisting for 3 years. He denied tobacco, betel nut, or alcohol use. Clinical examination revealed a firm indurated mass in the right floor of the mouth near the posterior tongue. He reported no weight loss, dysphagia, or dyspnea. Two punch biopsies were nondiagnostic, showing only a few atypical cytokeratin- and p63-positive cells. Due to the ambiguity of these initial small samples, a subsequent incisional biopsy was performed, which revealed invasive carcinoma but did not permit definitive classification. Immunohistochemistry showed CK7 positivity, focal CEA and p63 staining, diffuse GATA3 positivity, and rare equivocal CD117 staining; however, the limited depth and paucicellularity of the specimen again precluded definitive classification. Magnetic resonance imaging demonstrated a 3.3 × 1.3 × 2.6 cm contrast-enhancing mass involving the right tongue and mouth floor without regional lymph node metastasis (Figure 1). Positron emission tomography showed asymmetric hypermetabolism in the right tongue and mouth floor and focal uptake at the prior hepatic resection margin. Based on the clinical and radiologic features, which showed a slowly progressive, firm, contrast-enhancing mass involving the right tongue and floor of the mouth without regional lymphadenopathy, the differential diagnoses encompassed both primary salivary gland type malignancies and more common mucosal tumors. Minor salivary gland carcinomas, particularly SMA and adenoid cystic carcinoma, were considered because of the submucosal presentation and the CK7-positive, GATA3-expressing immunophenotype observed in the initial biopsies. Squamous cell carcinoma also remained a diagnostic consideration given its frequency in this anatomic region, although the CK7-dominant profile made this less typical. In view of the patient’s remote history of undifferentiated intrahepatic cholangiocarcinoma, metastatic disease was likewise included in the differential diagnosis, especially given the focal PET uptake at the previous hepatic resection site. Given that both punch and incisional biopsies were nondiagnostic and insufficient for definitive tumor classification, the primary operative goal was to achieve local control and obtain an adequate specimen for histopathological diagnosis. The patient therefore underwent wide excision of the right tongue and mouth floor tumor. Intraoperative frozen-section margin evaluations were all negative for malignancy. Because the excision created a soft-tissue defect of the floor of the mouth, reconstruction was performed using a fascia lata allograft to restore mucosal integrity and prevent tethering of the mobile tongue. Histopathologic evaluation revealed a highly infiltrative neoplasm extending deep into the skeletal muscle, characterized by prominent glandular and tubular structures composed of bland eosinophilic cuboidal cells positive for CK7 and outer myoepithelial cells showing p40 positivity on immunohistochemical staining, all embedded in a thick desmoplastic stroma (Figure 2). Numerous foci of perineural invasion were present. Surface dysplasia was absent; however, focal epithelial extension was present. Diffuse GATA3 positivity, focal p40/CK7 dual expression, HER2 negativity (score 0), and faint focal S100 staining in abluminal cells were observed. Laparoscopic biopsy of the hepatic site later revealed only fibrosis and chronic inflammation, excluding recurrent cholangiocarcinoma. Based on the morphology and immunohistochemical staining, a diagnosis of SMA was made. Because the surgical margins were involved, the patient subsequently underwent margin re-excision followed by adjuvant radiotherapy.

Figure 1.

Contrast-enhancing mass involving the right floor of the mouth and tongue on a coronal fat-suppressed T1-weighted image.

Figure 2.

(A) Pathological examination of SMA. The tumor is highly infiltrative, with neoplastic cells (arrows) embedded in desmoplastic stroma (yellow asterisks) and infiltrating in muscular tissue (black asterisk) (hematoxylin-eosin stain; original magnification ×100). (B) SMA shows a biphasic arrangement of bland flattened to cuboidal eosinophilic cells with well-defined outer myoepithelial and inner ductal layers (hematoxylin-eosin stain; original magnification ×100). Inset, Arrows highlight the inner ductal layers and arrowheads highlight outer myoepithelial cells (hematoxylin-eosin stain; original magnification ×400). (C) p40 positivity is present in outer myoepithelial cells (original magnification ×100). (D) CK7 shows denser staining in inner luminal cells (original magnification ×100). SMA, sclerosing microcystic adenocarcinoma.

SMA is a rare, low-grade malignant neoplasm primarily affecting the mucosal surfaces of the head and neck, presumed to originate from minor salivary glands.^1,2 It closely resembles microcystic adnexal carcinoma (MAC) of the skin histologically, characterized by narrow infiltrative cords, nests, and ductal structures of bland basaloid or cuboidal cells within a densely sclerotic or desmoplastic stroma, often with prominent perineural invasion.^2,3 In earlier literature, similar tumors involving the oral cavity or other mucosal regions of the head and neck were reported under a range of overlapping designations, such as MAC at extracutaneous locations, sclerosing sweat duct-like carcinoma, and syringomatous carcinoma. ⁴ In 2016, Mills et al. coined the term “sclerosing microcystic adenocarcinoma” to describe five MAC-like tumors arising in mucosal sites of the head and neck, which lacks the adnexal structures present in MAC.² Reported sites in the literature include the tongue, floor of the mouth, buccal mucosa, lip mucosa, nasopharynx, and, rarely, the parotid gland.^4,5 SMA is locally aggressive but indolent, with no reported locoregional recurrences or distant metastases in limited follow-up data.^4,6 Prior malignancies or immunosuppression status may play a role in SMA, as in our patient’s past history of cholangiocarcinoma, though no consistent risk factors are identified. ²

The decision-making surrounding cervical management warrants clarification. A therapeutic or elective neck dissection was not performed because SMA is recognized as a biologically indolent, low-grade malignant neoplasm with no documented cases of cervical lymph node metastasis in the published literature. Preoperative MRI and PET imaging in our patient also showed no radiologic evidence of nodal disease, supporting an observation approach. Importantly, at the time of the initial operation, a definitive diagnosis had not yet been established due to nondiagnostic biopsies; therefore, performing a prophylactic neck dissection without confirmed histology was not clinically justified. Once the final diagnosis of SMA was rendered, the absence of nodal involvement both on imaging and according to established disease biology supported proceeding without neck dissection.

Microscopically, SMA shows MAC-like low-power features with nests, cords, and tubules of bland tumor cells within dense desmoplastic stroma. It is biphasic, with ductal and peripheral myoepithelial cells, sometimes containing eosinophilic secretions. Collagenous stroma predominates; mitoses and high-grade features are absent, but perineural invasion is common. To date, no specific molecular alteration has been identified, and the immunohistochemical profile remains nonspecific. Diagnosis relies on histopathological evaluation and may be difficult in small biopsy specimens. ⁶ Margin assessment could also be particularly challenging due to the paucicellular nature of the tumor. ⁶ The differential diagnosis includes squamous cell carcinoma, adenoid cystic carcinoma, and hyalinizing clear-cell carcinoma, each of which may mimic components of SMA but typically demonstrates distinguishing features such as keratinization, cribriform architecture, or lack of biphasic differentiation. ⁴

SMA was not included in the 2017 World Health Organization (WHO) classification but was recognized as a distinct entity in the 2022 edition. ⁴ The rarity underscores the need for increased awareness among pathologists and clinicians to ensure accurate diagnosis and management, typically involving wide local excision with or without adjuvant radiation. ⁶