RESUMO
Parotid gland pathology represents a web of differential diagnoses. There are many complex cases that require extensive diagnostic tests for a complete and correct final pathology diagnosis. Currently the official classification of parotid gland tumors extends over more than 40 subtypes. We performed a query of the PubMed database regarding the use of molecular biology tests in performing a better characterization of the tumors in specific cases. By using fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR) or next-generation sequencing, the team managing complex cases can offer a personalized therapeutic solution. We review the molecular differential diagnosis according to published articles in the last 5 years for many types of parotid gland tumors ranging from benign to borderline malign tumors to malign aggressive tumors. Mucoepidermoid carcinoma is a distinct subtype of parotid malignancy that was the subject of a consistent number of articles. However, the molecular biology diagnosis techniques helped more in excluding the diagnosis of mucoepidermoid carcinoma, and probably retrospectively limiting the number of cases with this final diagnosis. In Romania, the molecular biology diagnosis is available only in limited research facilities and should receive more consistent funding that will make it available on a larger scale. The novelty of this scoping review is that we propose an algorithm for molecular differential diagnosis of the tumors that could be encountered in the parotid gland.
Assuntos
Neoplasias Parotídeas , Humanos , Neoplasias Parotídeas/diagnóstico , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/patologia , Diagnóstico Diferencial , Técnicas de Diagnóstico Molecular/métodos , Biomarcadores Tumorais/genética , Hibridização in Situ Fluorescente/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodosAssuntos
Carcinoma de Células Acinares , Neoplasias Parotídeas , Humanos , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/genética , Carcinoma de Células Acinares/patologia , Carcinoma de Células Acinares/genética , Fatores de Transcrição/genética , Masculino , Proteínas Ativadoras de GTPase/genética , Feminino , Glândula Parótida/patologia , Proteínas de Fusão Oncogênica/genética , Pessoa de Meia-IdadeAssuntos
Variante 6 da Proteína do Fator de Translocação ETS , Rearranjo Gênico , Neoplasias Parotídeas , Receptor trkC , Humanos , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/diagnóstico , Masculino , Feminino , Proteínas de Fusão Oncogênica/genética , Pessoa de Meia-Idade , Carcinoma/genética , Carcinoma/patologiaRESUMO
Infarction has rarely been reported in some types of salivary gland tumors. In this study, we present the first case of infarction occurring in salivary basal cell adenoma. A 62-year-old male presented with swelling in the left parotid region. Histopathological examination revealed extensive central necrosis surrounded by a rim of viable tumor tissue showing the typical histology of basal cell adenoma. Nuclear ß-catenin expression and the CTNNB1 p.I35T (c.104 T > C) mutation were identified in the tumor. A diagnosis of basal cell adenoma with central necrosis was made, and the postoperative period was uneventful. In addition, we review the literature on CTNNB1 I35T mutations in basal cell neoplasms of the salivary glands. Awareness of the possible occurrence of infarction and the high frequency of the unique mutation in basal cell adenoma may help in the differential diagnosis of salivary gland tumors.
Assuntos
Adenoma , Neoplasia de Células Basais , Neoplasias Parotídeas , Neoplasias das Glândulas Salivares , Masculino , Humanos , Pessoa de Meia-Idade , Glândula Parótida/patologia , Biomarcadores Tumorais/metabolismo , Adenoma/genética , Neoplasias das Glândulas Salivares/patologia , Infarto , Necrose , Mutação , Neoplasias Parotídeas/genética , beta Catenina/genéticaRESUMO
We describe a case of a myoepithelial carcinoma of the superficial parotid gland in a 46-year-old male harboring a novel CTCF::NCOA2 gene fusion. To our knowledge, this novel gene fusion has not been described previously in myoepithelial carcinoma. A 46-year-old male patient presented with a mass involving the superficial left parotid gland with extension into the external auditory canal (EAC) and erosion of the conchal cartilage. Histologically, the neoplasm was composed of uniform spindled, epithelioid/ovoid cells arranged in cords and nests within hyalinized to myxoid stroma. On immunohistochemistry (IHC), the tumor cells demonstrated patchy and variable staining for low molecular weight cytokeratin (CAM5.2), pan-cytokeratin (OSCAR), and S-100. Overall, the morphological and immunohistochemical attributes supported a locally aggressive tumor of myoepithelial differentiation consistent with myoepithelial carcinoma. Molecular analysis using a custom 115-gene gene panel by targeted RNA sequencing, showed an in-frame CTCF::NCOA2 fusion. In addition to reporting this novel fusion in myoepithelial carcinoma, we also discuss relevant differential diagnosis, and provide a brief review of NCOA2 gene function in both normal and neoplastic contexts.
Assuntos
Carcinoma , Mioepitelioma , Neoplasias Parotídeas , Masculino , Humanos , Pessoa de Meia-Idade , Glândula Parótida/patologia , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/química , Neoplasias Parotídeas/diagnóstico , Carcinoma/genética , Mioepitelioma/genética , Mioepitelioma/patologia , Queratinas/genética , Coativador 2 de Receptor Nuclear/genéticaRESUMO
BACKGROUND/AIM: SMARCB1(INI1)-deficient cutaneous carcinomas are an emerging subset of rare tumors, with only a few cases reported, making its diagnosis challenging. CASE REPORT: A 84-year-old male with a history of prostate adenocarcinoma and skin squamous cell cancer presented with a rapidly growing upper neck mass. Computed tomography (CT) and positron emission tomography (PET)/CT scans were suspicious of a salivary gland neoplasm of the parotid glands. Needle core biopsy of the right parotid gland mass showed poorly differentiated carcinoma. The patient underwent bilateral superficial parotidectomies and neck lymph nodes dissection. Histologically, the tumor showed rhabdoid and plasmacytoid morphology with diffuse loss of SMARCB1, positive deltaNp63 (p40), focally positive synaptophysin, and 80% of Ki67 index. Retrospectively, SMARCB1 deficiency carcinoma with squamous and neuroendocrine differentiation was confirmed in the prior skin lesion of the right frontal scalp. The patient had a poor prognosis even though post-surgical radiation therapy was given. CONCLUSION: We present a unique case of metastatic SMARCB1-deficient cutaneous carcinoma in the parotid glands with both squamous and neuroendocrine differentiation. This entity should be considered in any difficult-to-classify skin carcinoma, as timely definitive diagnosis will be mandatory for optimizing therapy.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Parotídeas , Neoplasias das Glândulas Salivares , Neoplasias Cutâneas , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Humanos , Masculino , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/diagnóstico , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Estudos Retrospectivos , Proteína SMARCB1 , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
A 15-year-old old Japanese male with a 2-month history of swelling of his left subauricular area was admitted to our department. A thumb-sized, hard mass with mild tenderness was palpated on the left parotid gland. Ultrasonography revealed a well-circumscribed, hypoechoic mass exhibiting heterogeneity in the left parotid gland measuring 1.7 × 1.5 × 1.3 cm. Computed tomography scan revealed a well-circumscribed, solid mass exhibiting slight peripheral enhancement in the left parotid gland. Magnetic resonance imaging revealed a hypointense mass in the left parotid gland on both T1- and T2-weighted images. Clinicoradiologic findings suggested a benign or low-grade malignant parotid tumor. The patient underwent left superficial parotidectomy with adequate safety margins. The facial nerve was identified and preserved. Neither facial paralysis nor tumor recurrence was observed as of 1 year postoperatively. Histologically, the nodule consisted of a vaguely nodular arrangement of variably sized ducts and acini in a hyalinized fibrous background with focal myxoid changes. The ductal/acinar component exhibited a bilayered arrangement of cuboidal luminal and flattened abluminal cells exhibiting a variety of epithelial proliferative patterns, including micropapillary and cribriform. Areas of oncocyte-like changes with intracellular coarse eosinophilic granules, apocrine-like feature, foamy/vacuolated changes, and clear cells were noted in the proliferating epithelium. Immunohistologically, the luminal cells were positive for gross cystic disease fluid protein-15. The Ki-67 labeling index was 2-3%. The histologic features and immunohistologic profile were consistent with sclerosing polycystic adenosis. Targeted next-generation sequencing of 160 cancer-related genes using the surgical specimen revealed no mutations, including known significant mutations in PTEN, PIK3CA, or PIK3R1.
Assuntos
Neoplasias Parotídeas , Fosfatidilinositol 3-Quinases , Adolescente , Humanos , Hiperplasia/patologia , Imageamento por Ressonância Magnética , Masculino , Mutação , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologiaRESUMO
In the absence of clear pathologic differences, clinical history may differentiate potential primary parotid squamous cell carcinomas (SCC) from metastases. The presence of an ultraviolet (UV) signature can distinguish between tumors of cutaneous and non-cutaneous origin. This study aimed to investigate rates of UV signature mutations in squamous cell carcinomas of the parotid gland as well as differences in clinical features between tumors of cutaneous and non-cutaneous origin. Clinical and pathologic data were collected from 71 patients with SCC involving the parotid gland, of which 48 had cutaneous, 10 had mucosal, and 13 had no history of SCC. In 34 available cases, genomic DNA was isolated from formalin-fixed paraffin-embedded tissue specimens and sequenced using a targeted hybrid capture 1213 gene panel. Tumor mutational burden and COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signatures were calculated. Most (74%) were UV-positive. Patients with UV-positive tumors were significantly older, white, and had higher rates of sun exposure. Patients with UV-negative tumors had a significantly higher mortality rate and shorter time to death: 6 (67%) died of disease with a median time to death of 9 months compared to 5 (20%) UV-positive patients who died of disease with a median time to death of 32 months. Pathologic features did not significantly vary by clinical history or UV status. The presence of a UV-signature combined with clinical history can be used to determine the primary source of SCC involving the parotid gland. UV-positivity may reflect a less aggressive disease course in an older population.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Parotídeas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/patologia , Humanos , Mutação , Glândula Parótida/patologia , Neoplasias Parotídeas/genética , Prognóstico , Neoplasias Cutâneas/patologiaRESUMO
Myoepithelial carcinoma (MECA) is a rare salivary gland (SG) neoplasm (0.1-0.45% of all SG tumors) that often presents with bland cytomorphology and can be misclassified as cellular pleomorphic adenoma (PA) or myoepithelioma. This is particularly challenging in MECA ex-PA cases, especially if tumor shows minimal to no capsular invasion. We report a rare case of a 76-year-old female; history of left superficial parotidectomy with diagnosis (outside hospital) of cellular PA, who re-presented 9 months post surgery with enlarging left parotid mass, neck lymphadenopathy and facial nerve deficits. FNAB of parotid and neck lymph node revealed cellular aspirates with loosely cohesive clusters of myoepithelial cells with occasional chondromyxoid stroma. Prior resection slides were reviewed, and diagnosis of MECA ex-PA was made. Patient underwent left radical parotidectomy, selective neck dissection, with facial nerve sacrifice (due to extensive encasing by tumor). Histology showed a multinodular tumor with pushing borders, zonal arrangement comprising of a hypocellular, necrotic/myxoid center, and a peripheral rim of myoepithelial cells, confirmed by positive S100, and p63. Tumor extensively infiltrated peri parotid soft tissues with multiple foci of lymphovascular and perineural invasion; and metastatic neck lymph nodes. Next generation sequencing revealed a novel TERT promoter mutation (c.-124C > T), not usually described in SG neoplasms. Further, PD-L1 immunohistochemistry showed positive expression, making patient eligible for anti-PDL-1 immunotherapy. This case highlights importance of recognizing the subtle malignant features of MECA in distinguishing it from benign mimics like PA. In addition, presence of TERT mutation opens a new arena for future research to explore potential treatment targets.
Assuntos
Adenocarcinoma , Adenoma Pleomorfo , Carcinoma , Mioepitelioma , Neoplasias Parotídeas , Neoplasias das Glândulas Salivares , Telomerase , Adenoma Pleomorfo/diagnóstico , Adenoma Pleomorfo/genética , Adenoma Pleomorfo/patologia , Idoso , Antígeno B7-H1 , Carcinoma/patologia , Erros de Diagnóstico , Feminino , Humanos , Mutação , Mioepitelioma/diagnóstico , Mioepitelioma/genética , Mioepitelioma/patologia , Neoplasias Parotídeas/diagnóstico , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Telomerase/genéticaRESUMO
Sclerosing polycystic adenoma (SPA) is a rare salivary gland neoplasm originally thought to represent a non-neoplastic lesion. Recently we have encountered an index case of apocrine intraductal carcinoma of parotid gland of 62-year-old man with invasive salivary duct carcinoma component arising from SPA, a combination of tumor entities that has never been published so far. Here, we further explore the nature of SPA by evaluating 36 cases that were identified from the authors' consultation files. The patients were 25 females and 11 males aged 11 to 79 years (mean, 47.8 y). All tumors originated from the parotid gland. Their size ranged from 11 to 70 mm (mean, 28 mm). Histologically, all cases revealed characteristic features of SPA, such as lobulated well-circumscribed growth, focal hyalinized sclerosis, presence of large acinar cells with abundant brightly eosinophilic intracytoplasmic granules, and ductal components with variable cytomorphologic characteristics, including foamy, vacuolated, apocrine, mucous, clear/ballooned, squamous, columnar and oncocyte-like cells. In all cases, there were foci of intraluminal solid and cribriform intercalated duct-like epithelial proliferations with variable dysplasia which were positive for S100 protein and SOX10, and fully enveloped by an intact layer of myoepithelial cells. In addition, 14/36 cases (39%) had focal intraductal cribriform and micropapillary apocrine-type dysplastic epithelial structures composed of cells positive for androgen receptors and negative for S100/SOX10. The intraductal proliferations of both types showed focal mild to severe dysplasia in 17 cases (17/36; 47%). Two cases showed overt malignant morphology ranging from high-grade intraductal carcinoma to invasive carcinoma with an apocrine ductal phenotype. Next generation sequencing using ArcherDX panel targeting RNA of 36 pan-cancer-related genes and/or a TruSight Oncology 170/500 Kit targeting a selection of DNA from 523 genes and RNA from 55 genes was performed. Tumor tissue was available for molecular analysis in 11 cases, and 9 (9/11; 82%) of them harbored genetic alterations in the PI3K pathway. Targeted sequencing revealed HRAS mutations c.37G>C, p.(Gly13Arg) (2 cases) and c.182A>G, p.(Gln61Arg) (2 cases), and PIK3CA mutations c.3140A>G, p.(His1047Arg) (3 cases), c.1633G>A, p.(Glu545Lys) (1 case), and c.1624G>A, p.(Glu542Lys) (1 case). Moreover, mutations in AKT1 c.49G>A, p.(Glu17Lys) and c.51dup, p.(Tyr18ValfsTer15); c.49_50delinsAG, p.(Glu17Arg) (as a double hit) were found (2 cases). In addition, germinal and somatic mutation of PTEN c.1003C>T, p.(Arg335Ter); c.445C>T, p.(Gln149Ter), respectively, were detected. Gene fusions were absent in all cases. These prevalent molecular alterations converging on one major cancer-related pathway support the notion that SPA is a true neoplasm with a significant potential to develop intraluminal epithelial proliferation with apocrine and/or intercalated duct-like phenotype. The name SPA more correctly reflects the true neoplastic nature of this enigmatic lesion.
Assuntos
Adenoma/enzimologia , Biomarcadores Tumorais/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação , Neoplasias Císticas, Mucinosas e Serosas/enzimologia , Neoplasias Parotídeas/enzimologia , Proteínas Proto-Oncogênicas c-akt/genética , Adenoma/genética , Adenoma/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Criança , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/patologia , PTEN Fosfo-Hidrolase/genética , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Fenótipo , Proteínas Proto-Oncogênicas p21(ras)/genética , Esclerose , Adulto JovemRESUMO
BACKGROUND: Fusions of neurotrophic tropomyosin receptor kinase genes NTRK1, NTRK2 and NTRK3 with various partner genes occur in both common and rare tumours and are of paramount predictive value due to the availability of very effective pan-Trk inhibitors like Larotrectinib and Entrectinib. Detection of NTRK fusions is mainly performed by fluorescence in situ hybridization (FISH) and next generation sequencing (NGS). The case described here showed a very unusual, but highly significant FISH signal pattern with an NTRK3 break apart probe, indicative of a functional NTRK3 rearrangement. CASE PRESENTATION: We describe here the case of a male patient who was originally diagnosed with an adenocarcinoma of the parotid gland without evidence of metastases. After the development of multiple lung metastases, an extensive immunohistochemical and molecular examination of archived tumour tissue including analysis of NTRK was performed. NTRK expression was detected by immunohistochemistry (IHC) and then comprehensively analysed further by FISH, quantitative reverse transcription PCR (RT-qPCR), and NGS. NTRK3 break apart FISH showed multiple and very faint single 3' signals in addition to fusion signals. Quantitative reverse transcription PCR and NGS confirmed an ETV6:exon5-NTRK3:exon15 fusion. Diagnosis was therefore revised to metastatic secretory carcinoma of the salivary gland, and the patient subsequently treated with Larotrectinib, resulting in persisting partial remission. CONCLUSIONS: Our findings underline the importance to be aware of non-canonical signal patterns during FISH analysis for detection of NTRK rearrangements. Very faint single 3' signals can indicate a functional NTRK rearrangement and therefore be of high predictive value.
Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Rearranjo Gênico , Hibridização in Situ Fluorescente , Proteínas de Fusão Oncogênica/genética , Neoplasias Parotídeas/genética , Adenocarcinoma/diagnóstico , Adulto , Humanos , Masculino , Fusão Oncogênica , Neoplasias Parotídeas/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
This case series reports familial cases of nodular oncocytic hyperplasia (NOH) diagnosed in a mother and her son, 15 years apart. A 39-year-old man presented in 2003 with a lump below his left ear. Magnetic resonance imaging (MRI) performed showed multifocal parotid nodules and a diagnosis of NOH was histopathologically confirmed following left total parotidectomy. Two years later, he represented with similar symptoms on the right side. NOH was diagnosed following excision of his right parotid gland. In 2018, his 73-year-old mother presented with left ear pain and a lump below her left ear. An MRI scan showed multiple lesions within both parotid glands and bilateral NOH was once again diagnosed following a left superficial parotidectomy and right total parotidectomy. We believe that this is the first reported case of bilateral familial NOH.
Assuntos
Adenoma Oxífilo , Neoplasias Parotídeas , Adenoma Oxífilo/patologia , Idoso , Feminino , Humanos , Hiperplasia/diagnóstico por imagem , Hiperplasia/patologia , Masculino , Mães , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/cirurgiaRESUMO
Salivary duct carcinoma of the parotid gland is a highly aggressive epithelial malignancy morphologically resembling high-grade, invasive, and in situ breast carcinoma. It can occasionally present with variable morphology making it diagnostically challenging in cases with unusual morphological components. Ancillary testing, particularly androgen receptor (AR) positivity on immunohistochemistry, can be very helpful in cases that demonstrate extensive squamous morphology, since AR positivity is uncommon in both the primary salivary gland and metastatic squamous cell carcinomas to the parotid. In this report, we describe a case of salivary duct carcinoma that showed only a squamous cell carcinoma component on the initial primary tumor site biopsy, as well as in subsequent contralateral neck lymph node and skin metastases. Apart from the variable morphology, the typical salivary duct and squamous cell carcinoma tumor components also showed significant immunohistochemical differences, including differential staining of human epidermal growth factor receptor 2/neu. The associated diagnostic pitfalls, distinct immunoprofiles of the tumor components, helpful adjuncts for making the correct diagnosis, and associated therapeutic implications are discussed.
Assuntos
Carcinoma Ductal/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Complexas Mistas/diagnóstico , Glândula Parótida/patologia , Neoplasias Parotídeas/diagnóstico , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Biópsia , Carcinoma Ductal/genética , Carcinoma Ductal/patologia , Carcinoma Ductal/terapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Análise Mutacional de DNA , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Mutação , Neoplasias Complexas Mistas/genética , Neoplasias Complexas Mistas/patologia , Neoplasias Complexas Mistas/terapia , Cuidados Paliativos/métodos , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/terapiaRESUMO
INTRODUCTION: Standardized systemic treatment options are lacking for carcinoma ex pleomorphic adenoma, which is a rare and aggressive tumor primarily found in salivary glands.Here we report the case of a 63-year-old male with carcinoma ex pleomorphic adenoma of the left parotid and parapharyngeal space harboring a neurotrophic receptor tyrosine kinase (NTRK) 2 fusion who was treated with a small molecule inhibitor that targets the tropomyosin receptor kinase (TRK) proteins. To the best of our knowledge, no similar case has been described in the literature so far. PATIENT CONCERNS: After multiple surgical resections and radiotherapy for localized cancer disease over several years, our patient again developed an increasing swelling and pain around the left ear and numbness of the left half of the face. DIAGNOSIS: Magnetic resonance imaging and positron emission tomography/computed tomography scans showed tumor recurrence in the left parotid, below the left ear, and in the parapharyngeal space, as well as metastases of the lungs and cervical lymph nodes. As data on the efficacy of systemic therapies for inoperable carcinoma ex pleomorphic adenoma are scarce, we performed a next-generation sequencing that revealed the presence of a hitherto unknown NTRK2 fusion. INTERVENTIONS: Treatment with the TRK inhibitor larotrectinib was initiated, which induced rapid symptom improvement. However, part of the tumor had to be removed shortly afterwards due to local progression. Molecular testing did not demonstrate any alterations accounting for resistance to larotrectinib, with maintenance of the NTRK2 fusion. OUTCOMES: Three months later, imaging confirmed mixed response. While the reason for this remains unknown, the patient is in good condition and continues to receive larotrectinib. CONCLUSION: It remains unclear why our patient showed mixed response to larotrectinib and further studies are needed to explore other possible mechanisms of resistance.
Assuntos
Adenoma Pleomorfo/tratamento farmacológico , Neoplasias Parotídeas/tratamento farmacológico , Neoplasias Faríngeas/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adenoma Pleomorfo/genética , Adenoma Pleomorfo/cirurgia , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Glicoproteínas de Membrana , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Proteínas de Fusão Oncogênica/genética , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/cirurgia , Neoplasias Faríngeas/genética , Neoplasias Faríngeas/patologia , Receptor trkBRESUMO
Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare malignancy in the thyroid: only 56 cases with histologic descriptions are reported in the literature and fewer reports describe the cytomorphology. Given the rarity of SMECE, data on the cytomorphologic and molecular features are limited. We report a case of a 53-year-old woman with a 5 cm left thyroid mass. Fine-needle aspiration (FNA) revealed atypia of undetermined significance and pathology of left thyroid lobectomy specimen showed SMECE. Additionally, a left pre-auricular lump was noted and FNA followed by left superficial parotidectomy showed basal cell adenoma. Next-generation sequencing showed point mutations in NTRK3 and NF1. Unlike salivary gland mucoepidermoid carcinoma, MAML2 translocations are not present in SMECE. Even though it is a rare entity, awareness of SMECE of the thyroid is important. In this case report we review the cytomorphologic, histologic, and molecular features.
Assuntos
Adenoma/patologia , Carcinoma Mucoepidermoide/patologia , Eosinofilia/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Parotídeas/patologia , Neoplasias da Glândula Tireoide/patologia , Adenoma/genética , Carcinoma Mucoepidermoide/genética , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/genética , Neurofibromina 1/genética , Neoplasias Parotídeas/genética , Mutação Puntual , Receptor trkC/genética , Neoplasias da Glândula Tireoide/genéticaRESUMO
Epithelial-myoepithelial carcinoma (EMCa) is a rare low-grade salivary malignancy. It is rare for EMCa to occur as the carcinomatous component of carcinoma ex-pleomorphic adenoma (PA). We examined one additional case of EMCa ex-PA, immunohistochemically and genetically. The patient was an 83-year-old female, who suffered from swelling of the right parotid region. Histologically, the tumor contained a hyalinized nodule, which displayed elastosis. The main tumor exhibited a bi-layered structure, involving inner ductal cells and clear outer myoepithelial cells. Immunostaining indicated that the inner cells were positive for epithelial membrane antigen, whereas the outer cells were positive for p40. On the genetic level, the carcinoma harbored no HRAS gene mutations, whereas fluorescence in situ hybridization (FISH) of the Pleomorphic Adenoma Gene1 showed splitting signals in the carcinomatous component. We diagnosed this case as EMCa ex-PA. It is necessary to differentiate EMCa ex-PA from myoepithelial carcinoma and clear cell carcinoma, and FISH is useful for such purposes.
Assuntos
Adenoma Pleomorfo/diagnóstico , Proteínas de Ligação a DNA/genética , Mutação , Neoplasias Parotídeas/diagnóstico , Adenoma Pleomorfo/genética , Adenoma Pleomorfo/patologia , Idoso de 80 Anos ou mais , Povo Asiático , Feminino , Humanos , Hibridização in Situ Fluorescente , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Proteínas Proto-Oncogênicas p21(ras)RESUMO
Secretory carcinoma (SC) of the salivary gland is a relatively newly described disease, separate from acinic cell carcinoma (ACC), which frequently displays ETV6-NTRK3 gene fusion. However, the differences between SC and ACC remain unclear. Here, histological reevaluation of 12 formerly diagnosed ACC cases was performed, which yielded a new diagnosis of SC in four cases due to a lack of obvious acinar-like cells. Immunohistochemically, phosphorylated signal transducer and activator of transcription 5 (p-STAT5) was expressed in SC but not in ACC, whereas discovered on GIST-1 (DOG1) was expressed in ACC but not in SC. Molecular analysis was possible in three SC cases, of which two showed the ETV6-NTRK3 fusion transcript on reverse-transcription polymerase chain reaction, as well as breaks in the ETV6 gene on fluorescence in situ hybridization. However, the remaining SC cases did not show this fusion transcript. Recently, several reports have suggested that SC might not be adequately diagnosed if the focus is placed solely on the ETV6-NTRK3 fusion gene due to genetic diversity. In this regard, immunohistochemistry of p-STAT5 and DOG1 is expected to be a useful alternative diagnostic tool to discriminate SC from ACC.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Acinares/diagnóstico , Imuno-Histoquímica , Proteínas de Fusão Oncogênica/genética , Neoplasias Parotídeas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anoctamina-1/análise , Anoctamina-1/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/patologia , Erros de Diagnóstico , Feminino , Heterogeneidade Genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/metabolismo , Glândula Parótida/patologia , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Fator de Transcrição STAT5/análise , Fator de Transcrição STAT5/metabolismo , Adulto JovemRESUMO
Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.
Assuntos
Carcinoma Ductal/patologia , Linfonodos/patologia , Neoplasias Parotídeas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Neoplasias Parotídeas/genéticaRESUMO
Porocarcinoma (synonym: malignant eccrine poroma) is a rare aggressive carcinoma type with terminal sweat gland duct differentiation. The squamous variant of porocarcinoma is even less frequent and might be indistinguishable from conventional squamous cell carcinoma (SCC). We herein describe the first case of a carcinoma presenting as a primary parotid gland malignancy in a 24-year-old male without any other primary tumor. Total parotidectomy and neck dissection were performed followed by adjuvant chemoradiation. The patient remained alive and well 10 months after diagnosis. Histology showed keratinizing SCC infiltrating extensively the parotid gland with subtle poroid cell features. Oncogenic HPV infection was excluded by DNA-based testing. NGS analysis using the TruSight RNA fusion panel (Illumina) revealed a novel YAP1-MAML2 gene fusion. This gene fusion was reported recently in a subset of cutaneous porocarcinoma and poroma. This case of poroid SCC (or squamoid porocarcinoma) adds to the differential diagnosis of SCC presenting as parotid gland tumor and highlights the value of molecular testing in cases with unusual presentation.