NKX3.1 Expression and Molecular Characterization of Secretory Myoepithelial Carcinoma (SMCA): Advancing the Case for a Salivary Mucous Acinar Phenotype.

BACKGROUND: Secretory myoepithelial carcinomas (SMCA) are rare, mucinous, signet ring predominant tumors with primitive myoepithelial features. While many mucinous salivary gland tumors have now been molecularly characterized, key drivers in SMCA have yet to be elucidated. Recently, NKX3.1, a homeodomain transcription factor implicated in salivary mucous acinar development was also shown in a subset of salivary mucinous neoplasms, salivary intraductal papillary mucinous neoplasms (SG-IPMN). To date, NKX3.1 expression has not been characterized in other mucinous salivary lesions. Here, we report molecular and extended immunophenotypic findings in SMCA and NKX3.1 expression in the context of other head and neck lesions. METHODS: We retrieved 4 previously reported SMCA, performed additional immunohistochemical and targeted next-generation sequencing (NGS). We also investigated the use of NKX3.1 as a marker for SMCA in the context of its prevalence and extent (using H-score) in a mixed cohort of retrospectively and prospectively tested head and neck lesions (n = 223) and non-neoplastic tissues (n = 66). RESULTS: NKX3.1 positivity was confirmed in normal mucous acini as well as in mucous acinar class of lesions (5/6, mean H-score: 136.7), including mucinous adenocarcinomas (3/4), SG-IPMN (1/1), and microsecretory adenocarcinoma (MSA) (1/1). All SMCA were positive. Fluorescence in situ hybridization for SS18 rearrangements were negative in all successfully tested cases (0/3). NGS was successful in two cases (cases 3 and 4). Case 3 demonstrated a PTEN c.655C>T p.Q219* mutation and a SEC16A::NOTCH1 fusion while case 4 (clinically aggressive) showed a PTEN c.1026+1G>A p.K342 splice site variant, aTP53 c.524G>A p.R175H mutation and a higher tumor mutation burden (29 per Mb). PTEN immunohistochemical loss was confirmed in both cases and a subset of tumor cells showed strong (extreme) staining for P53 in Case 4. CONCLUSION: Despite a partial myoepithelial phenotype, SMCA, along with mucinous adenocarcinomas/SG-IPMN and MSA, provisionally constitute a mucous acinar class of tumors based on morphology and NKX3.1 expression. Like salivary mucinous adenocarcinomas/SG-IPMN, SMCA also show alterations of the PTEN/PI3K/AKT pathway and may show progressive molecular alterations. We document the first extramammary tumor with a SEC16A::NOTCH1 fusion.

An atypical presentation of a Respiratory Epithelial Adenomatoid Hamartoma, a case report.

INTRODUCTION: Respiratory Epithelial Adenomatoid Hamartoma (REAH) is a benign disease that can resemble other malignant entities. Thus, it is essential to diagnose it accurately as the treatment approach differs, from radical surgeries in malignant cases, to a simple excision in hamartoma. We present an unusual case of bilateral REAH that was misdiagnosed, and hence it was treated aggressively. CASE REPORT: A 57-year-old male patient presented with anosmia, 2-years history of bilateral nasal obstruction, and was accompanied with a moderate headache. An impression of olfactory neuroblastoma was made after history taking physical examination, and imaging studies. The patient underwent Functional Endoscopic Sinus Surgery (FESS), excisional biopsy of the cribriform plate mass bilaterally, and superior septectomy. Histopathologic examination of the bilateral masses showed sinonasal polyposis with crypting of surface mucosa and pseudoglandular formation. A diagnosis of sinonasal polyps with REAH was established. The patient's nasal obstruction improved, with no recurrence of sinusitis ±â€¯polyposis. However, he still complains of anosmia after 2-years follow-up. CONCLUSION: Although REAH is a benign disease, it is critical to reach the correct diagnosis, in order to avoid aggressive treatment. Unfortunately, the preoperative investigations were not consistent with REAH, thus it was misdiagnosed and treated aggressively.

Diffuse Neurofibroma in a Patient with Unknown History of NF1.

Malignant peripheral nerve sheath tumor (MPNST) is a rare disease in the parotid gland with a poor prognosis in most cases. The disease most often develops in the setting of neurofibromatosis type 1 (NF1) but can also occur sporadically. Herein, we report a rare case of MPNST in the parotid gland, in a patient with no previous history of NF1. Initial investigations of the patient, which consisted of laboratory investigations, ultrasound imaging of the swelling, fine-needle aspiration (FNA), computed tomography (CT) scan, and magnetic resonance imaging (MRI) of the neck and swelling, were compatible with a benign pleomorphic adenoma of the parotid gland. However, intraoperatively, the dissection was challenging as the tumor was adherent to the neighboring tissue. A diagnosis of MPNST arising from a diffuse neurofibroma was established based on clinicopathologic features of the disease. The patient, who exhibited clinical features compatible with (NF1), proceeded for radiotherapy following surgery to continue his treatment.

Necrotizing tonsillitis caused by group C beta-hemolytic streptococci.

Tonsillitis and pharyngitis are among the most common infections in the head and neck. Viral tonsillitis is usually caused by enterovirus, influenza, parainfluenza, adenovirus, rhinovirus and Epstein-Barr virus (causing infectious mononucleosis). Acute bacterial tonsillitis is most commonly caused by group A beta-hemolytic streptococci. On the other hand, pseudomembranous and necrotizing tonsillitis are usually caused by fusiform bacilli and spirochetes. Here we report what is, to our knowledge, the first case of necrotizing tonsillitis caused by group C beta-hemolytic streptococci.

A Subset of Sinonasal Non-Intestinal Type Adenocarcinomas are Truly Seromucinous Adenocarcinomas: A Morphologic and Immunophenotypic Assessment and Description of a Novel Pitfall.

While sinonasal intestinal type adenocarcinoma (ITAC) is defined by an intestinal phenotype, non-intestinal type adenocarcinoma (non-ITAC) is traditionally viewed as a diagnosis of exclusion, despite previous implication of a seromucinous phenotype and similarity to sinonasal seromucinous hamartomas (SSH). We performed a comparison of clinicopathologic and immunophenotypic features of ITAC, non-ITAC and SSH using traditional discriminatory markers and new markers of seromucinous differentiation. Twenty-three non-ITAC, 17 ITAC, and 5 SSH were retrieved (1987-2014). As expected, ITAC occurred predominantly in the nasal cavity in elderly patients (mean age 65 years) with a striking male predilection (15:2). Regardless of grade/subtype, all ITAC were invariably CK20 and CDX2 positive, and many (11/15) showed some CK7 positivity. Non-ITAC occurred in younger individuals (mean age 51 years) with a slight female predilection (male to female ratio: 10:13) and showed diverse morphologic patterns and grades, some with morphologic similarity to SSH. SSH occurred in younger individuals (mean age 33 years). Non-ITAC and SSH were invariably CK7 positive and CK20 negative, however, 4/22 non-ITAC and 2/5 SSH showed squamoid morular metaplasia that aberrantly expressed CDX2 and co-expressed nuclear ß-catenin. Markers of seromucinous differentiation (S100, DOG1, and SOX10) were essentially absent in ITAC, but present to varying degrees in the majority of non-ITAC and all SSH. Thus, the term 'seromucinous adenocarcinoma' is the more appropriate designation for non-ITAC. Squamoid morules in non-ITAC and SSH may be an immunophenotypic pitfall given the aberrant CDX2 expression.

Secretory myoepithelial carcinoma: a histologic and molecular survey and a proposed nomenclature for mucin producing signet ring tumors.

Signet ring cell (mucin producing) adenocarcinoma is a rare low grade salivary gland malignancy. While currently designated as an adenocarcinoma, myoepithelial differentiation has been implied in previously reported cases. We herein perform a survey of our cases of signet ring cell adenocarcinoma and review the literature in order to refine categorization of this rare tumor. Five cases were retrieved. One was reclassified as a mammary analogue secretory carcinoma, leaving four that fulfilled the criteria for signet ring cell adenocarcinoma: the presence of prominent signet ring or vacuolated cells arranged in islands, interconnecting strands, cords or sheets in a myxoid or hyaline stroma, or pools of mucin. An extensive panel of histochemical and immunohistochemical stains and fluorescence in situ hybridization (FISH) (modeled after common phenotypes and molecular alterations seen in signet ring and myoepithelial tumors at other sites) was performed. The male-to-female ratio was 3:1. The mean age was 56 years (range 18-81). Sites involved included buccal mucosa (2), soft palate (1) and deep parotid (1). Perineural and angiolymphatic invasion were present in three and two cases respectively. One patient was lost to follow up and the remainder were alive and without disease at time of last follow up (mean 38 months). All cases showed mucicarmine positive vacuolated/signet ring cells embedded in a myxoid stroma. Three cases showed at least focal p63 staining and two cases showed positivity for calponin. Membranous E-cadherin was retained in all cases. FISH was negative for ETV6, EWSR1, and ALK1 rearrangements in all four cases. Based on the current series and the previously reported cases, it is evident that signet ring adenocarcinomas have a dual secretory and myoepithelial phenotype and thus as a whole more appropriately designated as 'secretory myoepithelial carcinoma.' They behave in a fairly indolent fashion and do not share the major molecular alterations seen in other signet ring and myoepithelial tumor types.

Primary sclerosing paraganglioma of the thyroid gland: a case report.

OBJECTIVES: Paragangliomas are neuroendocrine tumors derived from extra-adrenal paraganglionic cells of the autonomic nervous system. Paragangliomas of the thyroid are rare, with only 28 cases reported in the literature. The sclerosing paraganglioma variant, characterized by marked stromal sclerosis and hyalinization, has scarcely been reported. METHODS: A 36-year-old woman with a history of a 1-cm vagal schwannoma followed with serial magnetic resonance imaging presented with a new solitary 2.5-cm enhancing soft tissue mass in the left thyroid. RESULTS: Ultrasound examination of the thyroid revealed a hypoechoic, hypervascular, malignant-appearing mass. Two fine-needle aspirations were insufficient for diagnosis, and the mass was deemed a lesion of undetermined significance with subsequent indeterminate molecular testing. A diagnostic left thyroid lobectomy was performed, and pathologic examination revealed a lesion consistent with a sclerosing paraganglioma. CONCLUSIONS: Sclerosing paragangliomas are rare tumors, and only 1 case involving a primary thyroid mass has been reported in the literature. Although the sclerosing variant has features suggestive of malignancy, the true incidence of malignancy is unknown, given the rarity of its presentation. However, given the overall benign nature of paragangliomas, the sclerosing variant is also likely benign, despite its malignant features on ultrasound and histopathologic examination.