RESUMO
Adenoid cystic carcinoma is a malignant salivary gland neoplasm, commonly involving the major and minor salivary glands. Adenoid cystic carcinoma arising in the skull base region is considerably less common and is characterized by aggressive clinical behavior, perineural invasion, and intracranial extension. Classically, these tumors are composed of ductal and myoepithelial cells, arranged as tubules and cribriform structures, as well as in a solid pattern when higher in grade. The distinctive molecular findings in this tumor are the gene fusions involving the MYB/MYBL1 and NFIB genes. Squamous differentiation, trabecular, and macrocystic growth patterns are exceedingly rare in these tumors and when present can cause significant diagnostic challenges. Squamous differentiation, in particular, is considered by many to be an exclusion criterion for adenoid cystic carcinoma outside of cases with high-grade transformation. In addition, a similar-appearing tumor with squamous differentiation, namely human papillomavirus-related multiphenotypic sinonasal carcinoma, has recently been defined, further complicating this differential diagnosis. Recently, we have come across 3 cases of adenoid cystic carcinomas involving the sinonasal tract and skull base having extensive interconnecting trabecular growth, macrocysts, and squamous differentiation, yet demonstrating the signature fusions involving MYB-NFIB and MYBL1-NFIB by RNA sequencing. In this article, we describe the clinical, histomorphologic, and imaging findings of these cases and propose the appellation "metatypical adenoid cystic carcinoma" for this uncommon variant morphology.
Assuntos
Carcinoma Adenoide Cístico , Carcinoma de Células Escamosas , Seios Paranasais , Neoplasias das Glândulas Salivares , Carcinoma Adenoide Cístico/patologia , Humanos , Seios Paranasais/patologia , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Base do Crânio/patologiaRESUMO
Intraductal carcinoma of the salivary gland is a rare tumor characterized by intracystic proliferations of papillary, cribriform, and solid architecture of small uniform epithelial cells, reminiscent of ductal carcinoma in situ of the breast. Recent literature has identified 4 distinctive subtypes: the intercalated duct type, apocrine type, mixed/hybrid type, and oncocytic type, all with corresponding immunohistochemical and molecular findings. Although these tumors are typically in situ, as evidenced by a retained myoepithelial layer, they can demonstrate minimal invasion or, rarely, widespread invasive growth. Their overall prognosis is favorable, with few reported cases of recurrences and nodal metastases but no evidence of distant metastases.
Assuntos
Carcinoma in Situ/patologia , Carcinoma Intraductal não Infiltrante/patologia , Neoplasias das Glândulas Salivares/patologia , Carcinoma in Situ/classificação , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/genética , Carcinoma Intraductal não Infiltrante/classificação , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/genética , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases/genética , Proteínas de Ligação a DNA/genética , Diagnóstico Diferencial , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Mutação , Proteínas Nucleares/genética , Prognóstico , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias das Glândulas Salivares/classificação , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/genéticaRESUMO
Next-Generation Sequencing (NGS) is being utilized with increasing frequency in the characterization of salivary gland tumours. The potential scenarios which may be encountered by using this technique in routine practice will be outlined in further text by drawing from our own clinical experience. These include oncocytic mucoepidermoid carcinomas with unusual variant morphology (and negative MAML2 fluorescent in-situ hybridization results), a diagnosis of ameloblastoma changed to adenoid cystic carcinoma (due to MYBL1 fusion presence), a salivary duct carcinoma with an ETV6-NTRK3 fusion (otherwise seen in secretory carcinomas) and novel fusion partners such as EWSR1-BEND2 (otherwise seen in pancreatic neuroendocrine carcinomas). As NGS continues to develop and more widespread clinical implementation increases, we must be cognisant of the need for proper interpretation and in some cases verification using a secondary technique, the limitations of this technique, and the ethical dilemmas one faces when encountering a novel fusion.
Assuntos
Carcinoma Mucoepidermoide/diagnóstico , Proteínas de Fusão Oncogênica/genética , Neoplasias Parotídeas/diagnóstico , Transativadores/genética , Fatores de Transcrição/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Mucoepidermoide/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Hibridização in Situ Fluorescente/métodos , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/análise , Neoplasias Parotídeas/genética , Análise de Sequência de DNARESUMO
Primary squamous cell carcinomas (SCCs) of the middle ear and temporal bone are rare and usually keratinizing by morphology. Nonkeratinizing, basaloid SCCs arising in this area are exceedingly rare, and, due to the anatomic proximity to the skull base, nasopharynx, and nasal sinuses, the differential diagnosis is broad. Most tumors with squamous differentiation arising in these subsites are either viral-induced (human papillomavirus/Epstein-Barr virus) or rarely may have specific molecular alterations (BRD4-NUT, EWSR1-FLI translocations). Occasional tumors are negative for these findings, and their pathogenesis is unknown. A recently discovered DEK-AFF2 fusion was clinically detected in a series of 2 cases known to the authors. This fusion has been previously reported in the literature in a patient with a base of skull tumor who was an exceptional responder to programmed cell death protein 1 inhibitor therapy. We examine here the histomorphologic and molecular findings of 2 additional cases of an emerging entity. Two male patients were identified. Each had a primary middle ear/temporal bone mass with locally advanced disease. The histology was reviewed, and immunohistochemistry was performed. RNA-based next-generation sequencing was performed for clinical detection of diagnostic or actionable fusions. Both patients had basaloid/nonkeratinizing tumors on biopsy. They were positive for markers of squamous differentiation (HMWK, CK5, and p40). By RNA sequencing, they demonstrated the presence of a DEK-AFF2 fusion and were negative for EWSR1 and NUT translocations. The DEK-AFF2 fusion may define a novel diagnostic category of middle ear and temporal bone nonkeratinizing/basaloid SCCs. This fusion also may represent a potential avenue for immunotherapy in these patients. Further studies are needed to fully explore whether this fusion defines a location-specific clinicopathologic entity.
Assuntos
Biomarcadores Tumorais/genética , Proteínas Cromossômicas não Histona/genética , Neoplasias da Orelha/genética , Orelha Média , Fusão Gênica , Neoplasias de Cabeça e Pescoço/genética , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Neoplasias Cranianas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Osso Temporal , Neoplasias da Orelha/patologia , Neoplasias da Orelha/cirurgia , Orelha Média/patologia , Orelha Média/cirurgia , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Neoplasias Cranianas/patologia , Neoplasias Cranianas/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Osso Temporal/patologia , Osso Temporal/cirurgiaRESUMO
Sclerosing odontogenic carcinoma is a rare locally destructive neoplasm with many histologic mimics. Here the diagnostic challenges are presented of a case of sclerosing odontogenic carcinoma with variable histologic features, including unusual and unexpected negative immunostaining for CK19.
Assuntos
Carcinoma/patologia , Neoplasias Maxilares/patologia , Segunda Neoplasia Primária/patologia , Tumores Odontogênicos/patologia , Carcinoma/terapia , Carcinoma Hepatocelular , Humanos , Neoplasias Hepáticas , Masculino , Neoplasias Maxilares/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Segunda Neoplasia Primária/terapia , Tumores Odontogênicos/terapiaRESUMO
BACKGROUND: The objective of this study was to evaluate the influence of papillary features on risk of malignancy (ROM) within the Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance (AUS-FLUS) Bethesda System for Reporting Thyroid Cytopathology (BSRTC) diagnostic category. METHODS: A Retrospective review of cases with an AUS-FLUS diagnosis that underwent a thyroidectomy was carried out, and cases were subcategorized based upon the presence of papillary features. RESULTS: For the entire study population there were 93 (22%) of 427 FNAB specimens that had an AUS-FLUS diagnosis, and a 32% associated ROM. Papillary features were identified in 44 FNAB specimens (47% of the AUS-FLUS cases or 10% of the entire study population), and when present had a 45% ROM. The 49 FNAB specimens (53%) that did not exhibit papillary features had a significantly lower ROM (20%) than those that did have papillary features (pâ¯=â¯0.0069). CONCLUSIONS: The presence of papillary features in a thyroid FNAB with an AUS-FLUS diagnosis is common, and is associated with a higher ROM than is currently suggested by the BSRTC.
Assuntos
Carcinoma Papilar, Variante Folicular/patologia , Lesões Pré-Cancerosas/patologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adulto , Colúmbia Britânica , Carcinoma Papilar, Variante Folicular/cirurgia , Citodiagnóstico , Feminino , Humanos , Masculino , Lesões Pré-Cancerosas/cirurgia , Estudos Retrospectivos , Medição de Risco , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
BACKGROUND: The objective of this study was to determine if patient age and/or gender significantly alter the risk of thyroid malignancy in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) diagnostic categories. METHODS: A retrospective review of 291 sequential patients that underwent thyroid nodule fine needle aspiration biopsy (FNAB) and subsequent surgery at a single center was carried out. Cases were grouped according to age (55 years and older versus younger than 55 years) and gender. The cancer risk was calculated for each BSRTC diagnostic group. A p-value <0.05 was not considered statistically significant. RESULTS: The study population was composed of 291 patients (227 females and 64 males). Histopathology diagnosed cancer in 113 cases (39%). The cancer risk was significantly increased in cases with a BSRTC diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in patients younger than 55 years of age (36.8% vs 7.4%, p=0.0082). CONCLUSIONS: Though thyroid cancer was significantly more common in males (p=0.021), gender did not significantly influence specific BRSTC diagnostic category cancer risk estimation. A BSRTC AUS/FLUS diagnosis is associated with an increased cancer risk in younger patients.