Perithyroidal Salivary Gland Acinic Cell Carcinoma: Morphological and Molecular Attributes of a Unique Lesion

Head and Neck Pathology https://doi.org/10.1007/s12105-020-01187-3 CASE REPORTS Perithyroidal Salivary Gland Acinic Cell Carcinoma: Morphological and Molecular Attributes of a Unique Lesion C. Christofer Juhlin1,2 · Sylvia L. Asa3 · Kenbugul Jatta2 · Homeyra Naserhojati Rodsari2 · Ivan Shabo4,5 · Felix Haglund1,2 · Brett Delahunt6 · Hemamali Samaratunga7 · Lars Egevad1,2 · Anders Höög1,2 · Jan Zedenius4,5 Received: 22 May 2020 / Accepted: 31 May 2020 © The Author(s) 2020 Abstract Rarely, salivary gland tumors such as mucoepidermoid carcinoma, mammary analogue secretory carcinoma and mucinous carcinoma arise as primary tumors from ectopic or metaplastic salivary gland tissue adjacent to or within the thyroid gland. We report for the frst time a case of primary salivary acinic cell carcinoma (AcCC) adjacent to the thyroid gland in a 71-year-old female patient with Crohns disease and a previous history of malignant melanoma. Following the development of a nodule adjacent to the left thyroid lobe, a fne-needle aspiration biopsy was reported as consistent with a follicular lesion of undetermined signifcance (Bethesda III). A left-sided hemithyroidectomy was performed. A circumscribed lesion measuring 33 mm was noted adjacent to the thyroid and trapping parathyroid, it was composed of solid nests and glands with microcystic and follicular patterns. The tumor was negative for thyroid, parathyroid and paraganglioma markers, but positive for pan-cytokeratins, CK7, CD10, CD117, androgen receptor and HNF-beta. A metastasis of a thyroid-like renal cell carcinoma was suspected but ruled out, and the patient had no evident lesions on extensive radiology of the urogenital, pulmonary and GI tracts. Based on the morphology, a diagnosis of AcCC was suggested, and confrmed with DOG1 and PAS-diastase staining. Molecular analyses pinpointed a constitutional ASXL1 variant of uncertain signifcance, but no fusion events. The patient had no radiological or clinical evidence of parotid, submandibular or sublingual tumors postoperatively, and the excised lesion was therefore assumed to be a primary tumor. We here detail the morphological and immunopheno- typic profle of this previously undescribed perithyroidal tumor. Keywords Acinic cell carcinoma · Thyroid · Mutation · Gene fusion Introduction * C. Christofer Juhlin Although the bulk of thyroid tumors are derived from the [email protected] follicular epithelium, a number of unusual lesions from stromal or ectopic tissue components have been reported, 1 Department of Oncology-Pathology, Karolinska Institutet, including angiosarcoma, parathyroid tumors, paragangli- Stockholm, Sweden oma, peripheral nerve sheath tumors, solitary fbrous tumors 2 Department of Pathology and Cytology, Karolinska and thymomas, to name a few [1]. Moreover, rare cases of University Hospital, Stockholm, Sweden salivary gland tumors have also been described within or 3 University Hospitals Cleveland Medical Center, Case adjacent to the thyroid gland, including mucoepidermoid Western Reserve University, Cleveland, Ohio, USA carcinoma, sclerosing mucoepidermoid carcinoma with 4 Department of Breast, Endocrine Tumors and Sarcoma, eosinophilia, mammary analogue secretory carcinoma and Karolinska University Hospital, Stockholm, Sweden mucinous carcinoma [1–7]. These malignant epithelial neo- 5 Department of Molecular Medicine and Surgery, Karolinska plasms are thought to arise in ectopic salivary gland tissue Institutet, Stockholm, Sweden and are histologically identical to those arising in salivary 6 Department of Pathology and Molecular Medicine, glands, but often display focal expression of thyroid-related University of Otago, Wellington, New Zealand markers such as TTF1, PAX8 and thyroglobulin [1]. From 7 Department of Molecular and Cellular Pathology, University a prognostic perspective, these tumors are often associated of Queensland, Brisbane, Australia Vol.:(0123456789)1 3 Head and Neck Pathology with poor patient outcome due to the development of histological, immunohistochemical and molecular land- regional and distant metastases [1, 8]. scape of this rather unique manifestation. Acinic cell carcinoma (AcCC) is a low-grade malignant neoplasm that almost exclusively occurs in the major salivary glands, especially the parotid gland, and is usually diagnosed on cytological examination following a fne nee- Case report dle aspiration biopsy (FNAB) [9]. Besides being primarily known as a salivary gland tumor, AcCC also occurs in the The patient was a 71-year-old female of Swedish ethnicity. pancreas where it derives from pancreatic acinar cells. Sali- She had a medical history of insulin-treated type 2 diabe- vary-type AcCCs have also been described in the lung, stom- tes, salazopyrine-treated Crohn’s disease and pelvospon- ach, prostate and breast [9–13]. The tumor is predominantly dylitis. She was previously administered infiximab, but found in women, and the usual age at diagnosis is > 50 years this was later changed to rituximab. In 2008, she was diag- [9, 14]. Previous radiation exposure has been described as nosed with a R0 resected amelanotic malignant melanoma a risk factor, and a hereditary link has also been suggested of the left forearm, Breslow’s depth 3 mm, Clark level IV, for small subsets of cases [15, 16]. Although slow growing, with no synchronous metastases. As part of the clinical AcCCs carry potential for metastatic spread, and long-term follow-up procedures, the patient was screened for relapses follow-up is recommended for most tumors following surgi- by various imaging techniques, and in July 2019, a com- cal excision. Histologically, AcCCs usually display a solid, puterized tomography (CT) of the thorax and abdomen micro-cystic, papillary or follicular growth pattern, and displayed an incidentally discovered 24 mm nodule that often display immunoreactivity for broad-spectrum keratins, was assumed to be a lymph node adjacent to the caudal DOG1 and CD117 (c-Kit) [17–22]. Moreover, cytoplasmic aspect of left thyroid lobe (Fig. 1). Shortly afterwards, the droplets of mucin visualized through a Periodic acid-Shif patient was referred to our hospital. An ultrasonography- stain with diastase (PAS-D) have also been described as guided fne needle aspiration biopsy (FNAB) of this mass diagnostic [18, 23]. was performed, and the cytology report described hyper- Given the rarity of AcCC, the underlying genetics driv- plastic follicular thyroid epithelium in groups of varying ing the development of these tumors have only partly been sizes, consistent with a follicular lesion of undetermined deciphered. Distinct cytogenetic aberrancies have been signifcance (Bethesda III) (Fig. 2). A separate FNAB of described, including deletions covering the short arm of the superior aspect of the lobe was consistent with fol- chromosome 6 [24]. Moreover, dysregulation of Rb-medi- licular nodular disease. When the patient was seen at the ated growth suppression has also been suggested as a con- endocrine surgery department, she was clinically and bio- tributing event [25]. To add on this, a recent study observed chemically euthyroid. A decision was made for a diagnos- HTN3-MSANTD3 fusions in a subset of salivary gland tic left-sided hemithyroidectomy, which was performed AcCCs with an indolent clinical course [26]. two weeks later, in which the mass and thyroid lobe were In this report, we report a case of AcCC clinically removed en bloc. The operation time was 50 min, and the presenting as a thyroid mass, and portray the clinical, procedure was complication-free. Fig. 1 Preoperative computerized tomography (CT) scan of the supe- VI. The image on the right is taken caudal to that on the left and rior thoracic inlet. The thyroid gland is marked by a white arrowhead, highlights the maximum diameter of the mass, reaching the superior and the white arrow designates the adjacent 24 mm lesion originally thoracic aperture believed to constitute an enlarged perithyroidal lymph node in level 1 3 Head and Neck Pathology the lobe, frmly attached to the thyroid, there was a well circumscribed tumor that measured 33 × 33 × 25 mm and was macroscopically demarcated from the adjacent thyroid tissue and displayed a pale yellow, homogenous cut surface. The thyroid lobe exhibited a variegated cut surface suggestive of follicular nodular disease with hemorrhage. Microscopi- cally, the well-delineated, partially encapsulated tumor was separate from the adjacent thyroid tissue (Fig. 3). Focally, normal parathyroid tissue was seen at the tumor periphery entrapped in the tumor capsule. The tumor was composed of solid nests and glandular formations with micro-cystic and follicular patterns, and the tumor cells displayed monomor- phic nuclei and abundant eosinophilic cytoplasm, which was granulated and vacuolated (Fig. 3). A PAS diastase (PAS-D) stain confrmed the presence of small cytoplasmic PAS-D positive droplets (Fig. 4), which were not evident by routine hematoxylin and eosin (H&E) staining. Immunohistochemical analyses (Fig. 4) confrmed the tumor as derived from non-thyroidal tissues, as no immunoreactivity was noted for TTF1, PAX8, thyroglobulin, chro- mogranin A, calcitonin and CEA. Parathyroid diferentiation was also excluded, as the tumor was negative for PTH and GATA3, while retained immunoreactivity was noted within the surrounding parathyroid cells. The tumor stained for pan-cytokeratins (CKMNF) and CK7, but not CK20, and there was focal EMA positivity. Synaptophysin and AFP yielded equivocal immunoreactivity. Negativity

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