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INTRODUCTION: Superficial non-ampullary duodenal epithelial tumors (SNADETs) include low-grade adenoma (LGA) and high-grade adenoma or carcinoma (HGA/Ca) and are classified into two different epithelial subtypes, gastric-type (G-type) and intestinal-type (I-type). We attempted to distinguish them by endoscopic characteristics including magnifying endoscopy with narrow-band imaging (M-NBI). METHODS: Various endoscopic and M-NBI findings of 286 SNADETs were retrospectively reviewed and compared between G- and I-types and histological grades. M-NBI findings were divided into four patterns based on the following vascular patterns; absent, network, intrastructural vascular (ISV), and unclassified. Lesions displaying a single pattern were classified as mono-pattern and those displaying multiple patterns as mixed-pattern. Lesions showing CDX2 positivity were categorized as I-types and those showing MUC5AC or MUC6 positivity were categorized as G-types based on immunohistochemistry. RESULTS: Among 286 lesions, 23 (8%) were G-type and 243 (85%) were I-type. More G-type lesions were located oral to papilla (91.3 vs. 45.6%, p < 0.001), and had protruding morphology compared to those of I-types (65.2 vs. 14.4%, p < 0.001). The major M-NBI pattern was ISV in G-type (78.2 vs. 26.3%, p < 0.001), and absent for I-type (0 vs. 34.5%, p = 0.003). Three endoscopic characteristics; location oral to papilla, protruding morphology, and major M-NBI pattern (ISV) were independent predictors for G-type. Mixed-pattern was more common in HGA/Ca than LGA for I-type (77.0 vs. 58.8%, p = 0.01); however, there was no difference for those in G-type. CONCLUSION: Endoscopic findings including M-NBI are useful to differentiate epithelial subtypes.
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INTRODUCTION: Recently, detection of superficial non-ampullary duodenal epithelial tumors (SNADETs) including adenomas and superficial duodenal carcinomas has increased. Various endoscopic treatment methods have also been reported for SNADETs, but there are few reports on the natural history. The aim of this study was to analyze factors related to tumor growth and determine the characteristics of SNADETs which need early therapeutic intervention. METHODS: A single-center, retrospective study was performed on medical records of 309 patients with SNADETs who underwent endoscopic or surgical resection between January 2010 and May 2021. Of these, 41 patients who were followed up for more than one year by endoscopy were analyzed. The primary outcome was analysis of the tumor growth speed. Secondary outcomes were the relationship between the tumor growth speed and mucin phenotype, tumor size and findings of magnifying endoscopy with narrow-band imaging (M-NBI). RESULTS: The observation period was 24 months (13-182). Tumor growth speed was 1.1 mm/year (0-21.6). Tumor diameter >10 mm at first detection (P=0.004; Odds ratio 19.5(2.03-186.96)) and mixed-type by M-NBI (p=0.036; Odds ratio 9.69(1.05-89.88)) were identified as risk factors of tumors growing at a rate of >3 mm/year. There was no statistically significant difference in the speed of tumor growth between the different mucin immunohistochemical phenotype. CONCLUSION: Initial tumor size and findings of M-NBI are useful to predict tumor growth and consider early intervention.
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Salivary gland tumors (SGT) display morphological diversity and pose diagnostic challenges. Preoperative fine needle aspiration cytology (FNAC) is a minimally invasive and efficient diagnostic test. However, due to the limited sample size, the final diagnosis may not be established based on FNAC alone. Although cytomorphology and architecture are usually preserved on FNAC, morphologic changes specific to FNAC can complicate the diagnosis. The Milan System for Reporting Salivary Gland Cytopathology categorizes complex FNAC interpretations. Because the cytological diagnosis is closely linked to the histological diagnosis, a multidimensional approach considering the possibility of several differential diagnoses is necessary. From the standpoint of treatment, distinguishing high-grade malignancy from low-grade malignancy is more important than distinguishing malignancy from benign tumors.
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Neoplasias das Glândulas Salivares , Humanos , Biópsia por Agulha Fina , Citodiagnóstico/métodos , Diagnóstico Diferencial , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Glândulas Salivares/patologiaRESUMO
The differential diagnosis of salivary gland lesions with epithelial components and lymphoid stroma is often challenging. Salivary gland carcinoma with tumor-associated lymphoid proliferation, tumors composed of both epithelial and lymphoid components, lymphoid neoplasms in the salivary gland, and inflammatory lesions are all included in this category. It encompasses inflammatory lesions and neoplastic lesions. With the exception of Warthin tumors, these lesions are rare, making them more difficult to diagnose. Carcinoma showing thymus-like elements has recently been reported in the salivary gland. Similar to thymic carcinoma, tumor cells are positive for CD5 and are accompanied by T lymphocytes.
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Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Diagnóstico Diferencial , Glândulas Salivares/patologia , Adenolinfoma/patologia , Adenolinfoma/diagnósticoRESUMO
High-grade carcinomas of the salivary glands are a group of several tumor entities with highly malignant histologic appearances, and have an aggressive biological behavior accompanied by poor a prognosis. In general, they require more intensive treatment than low- or intermediate-grade carcinomas. High-grade salivary carcinomas are rare and the microscopic features often overlap between different tumor types, making an appropriate diagnosis challenging in daily practice settings. However, with recent rapid advances in molecular pathology and molecular-targeted therapy in this field, there is a growing need to properly classify tumors, rather than just diagnosing the cases as "high-grade carcinomas". This leads to specific treatment strategies. In this article, we review representative high-grade salivary gland carcinomas, including salivary duct carcinoma and its histologic subtypes, high-grade mucoepidermoid carcinoma, solid-type adenoid cystic carcinoma, and high-grade transformation of low- or intermediate-grade carcinomas, and discuss their differential diagnoses and clinical implications. Other rare entities, such as neuroendocrine carcinoma, NUT carcinoma, and metastatic carcinoma, should also be considered before diagnosing high-grade carcinoma, NOS. Of these tumors, salivary duct carcinoma has received the most attention because of its strong association with androgen deprivation and anti-HER2 therapies. Other tumor-type-specific treatments include anti-TRK therapy for high-grade transformation of secretory carcinoma, but further therapeutic options are expected to be developed in the future. It should be emphasized that detailed histological evaluation with adequate sampling, in addition to the effective use of molecular ancillary tests, is of the utmost importance for a suitable diagnosis.
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Tomada de Decisão Clínica , Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/terapia , Gradação de Tumores , Carcinoma/patologia , Carcinoma/diagnóstico , Carcinoma/terapia , Diagnóstico DiferencialRESUMO
Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.
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Branchioma is a rare benign neoplasm occurring in the lower neck. Occurrence of malignant neoplasms arising in branchioma is extremely rare. Here, we report a case of adenocarcinoma arising in branchioma. A 62-year-old man had a right supraclavicular mass measuring 7.5 cm in diameter. The tumor contained an adenocarcinoma component encapsulated in a benign branchioma component. The adenocarcinoma component consisted of high- and low-grade components, with the former accounting for 80% of the adenocarcinoma. The high-grade component was immunohistochemically characterized by diffuse strong p53 expression, while the low-grade component and branchioma component were negative for p53. Targeted sequencing analysis for the branchioma and adenocarcinoma components revealed that the adenocarcinoma component harbored pathogenic mutations in KRAS and TP53. No definitive oncogenic drivers were detected in the branchioma component. Based on these immunohistochemical and molecular findings, we suggest that the KRAS mutation contributed to the pathogenesis of the adenocarcinoma, and the TP53 mutation played a key role in the transition from low-grade to high-grade adenocarcinoma.
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Adenocarcinoma , Branquioma , Masculino , Humanos , Pessoa de Meia-Idade , Branquioma/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/patologia , MutaçãoRESUMO
BACKGROUND: Polymorphous adenocarcinoma is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of polymorphous adenocarcinoma-associated genes, such as PRKD1/2/3, ARID1A, and DDX3X, in a large cohort of Japanese patients with polymorphous adenocarcinoma. METHODS: We examined the cases of 36 Japanese patients with salivary gland polymorphous adenocarcinoma and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for polymorphous adenocarcinoma-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations. RESULTS: This study revealed the indolent clinical course of polymorphous adenocarcinoma with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (23.3%). Twenty cases (55.6%) of polymorphous adenocarcinoma (but none of the mimics) exhibited alterations in at least one polymorphous adenocarcinoma-associated gene. Rearrangement of polymorphous adenocarcinoma-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (p = 0.0005), the presence of prominent nucleoli (p = 0.0003), and ARID1A split positivity (p = 0.004) were independent risk factors for disease-free survival. CONCLUSION: Japanese patients with polymorphous adenocarcinoma showed clinicopathological features similar to those reported in Western countries. This study disclosed that polymorphous adenocarcinoma-associated genetic alterations were common and specific findings in polymorphous adenocarcinomas. The diagnostic role and possible prognostic significance of polymorphous adenocarcinoma-associated genetic alterations in polymorphous adenocarcinomas were suggested.
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Adenocarcinoma , Neoplasias das Glândulas Salivares , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Humanos , Hibridização in Situ Fluorescente , Japão , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologiaRESUMO
Non-sebaceous lymphadenoma is a rare benign salivary gland tumor comprised of non-sebaceous epithelial cells and lymphoid tissue. Although its clinicopathological features have been described, its histogenesis and genetic background have not yet been elucidated. MAML2 rearrangement and the resultant CRTC1/3-MAML2 fusion gene are well-known specific genetic changes in mucoepidermoid carcinoma. Here, we present a case of lymphoepithelial tumor characterized by histomorphology of the non-sebaceous lymphadenoma and CRTC1-MAML2 fusion gene. The patient was an 83-year-old woman with an 8-year history of a solid, well-circumscribed tumor in the parotid gland. Histologically, the tumor was surrounded by thin fibrous connective tissue and was composed of tubular-cystic and solid nests of epithelial cells equally distributed in the lymphoid tissue. The histological features were suggestive of non-sebaceous lymphadenoma. Although the histomorphology was not consistent with mucoepidermoid carcinoma, a diagnosis of non-sebaceous lymphadenoma-like mucoepidermoid carcinoma was made based on the presence of the CRTC1-MAML2 fusion gene. The histological features alone could not establish the diagnosis, and ancillary molecular analysis was required.
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Carcinoma Mucoepidermoide , Neoplasias das Glândulas Salivares , Idoso de 80 Anos ou mais , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/patologia , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Proteínas Nucleares/genética , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Transativadores/genéticaRESUMO
Microsatellite instability (MSI)-high status is associated with good responsiveness to immune checkpoint inhibitors. Although MSI-high status has been actively investigated in pediatric brain tumors, studies of other pediatric solid tumors are lacking. Among 334 consecutive pediatric patients with solid tumors, we retrospectively analyzed formalin-fixed paraffin-embedded tumor tissues of 36 of 74 patients (49%) who died of disease. We assessed the MSI status in these tissues using five multiplexed markers. The results revealed that none of the patients had an MSI-high status. These results indicate that MSI-high status is a rare event in pediatric patients with refractory/relapsed solid tumors.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1998266.
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Instabilidade de Microssatélites , Neoplasias , Criança , Reparo de Erro de Pareamento de DNA , Humanos , Neoplasias/genética , Estudos RetrospectivosRESUMO
Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the "solid tumor component" has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease-free, and distant metastasis-free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease-free or distant metastasis-free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC.
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Carcinoma Adenoide Cístico/diagnóstico , Neoplasias das Glândulas Salivares/diagnóstico , Glândulas Salivares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Glândulas Salivares/cirurgia , Adulto JovemRESUMO
AIMS: Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4-RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27-RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC. METHODS AND RESULTS: Six IDCs with oncocytic changes were retrieved from the authors' archives, from three men and three women ranging in age from 45 to 75 years (mean, 63 years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1-23 months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33-RET in two of six cases, NCOA4-RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations. CONCLUSIONS: Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.
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Carcinoma Intraductal não Infiltrante , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias das Glândulas Salivares , Fatores de Transcrição/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Ductal/diagnóstico , Carcinoma Ductal/genética , Carcinoma Ductal/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mutação , Fusão Oncogênica , Células Oxífilas/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia , Análise de Sequência de RNARESUMO
The gastrointestinal tract is a rare site for metastatic lung cancer. Programmed cell death-ligand 1 (PD-L1) expression in lung cancer is a biomarker for the response to anti-PD-1/PD-L1 therapy. We investigated clinicopathological features and PD-L1 expression in 25 gastrointestinal metastatic tumors from the lung and primary adenocarcinoma of the small bowel. The small bowel was the most common site (16/25; 64%) of gastrointestinal tract lung cancer metastasis. A total of 19 (76%) of the gastrointestinal metastasis showed PD-L1 expression in ≥5% of tumor cells, with 14 (56%) showing high expression levels (≥50%). In contrast, 21 (84%) expressed PD-L1 in ≥5% immune cells, including 4 (16%) showing a high expression levels (≥50%). The PD-L1 expression on tumor cells and immune cells in primary lung cancer and corresponding gastrointestinal metastasis was concordant in 13 (68%) and 11 (58%) of the 19 paired cases, respectively. Small-bowel metastasis of lung cancer was characterized by a higher incidence of perforation (31% vs. 0%), ulcerated mass (83% vs. 60%), and neoplastic PD-L1 expression (75% vs. 0%) compared to primary small-bowel adenocarcinoma. Gastrointestinal metastasis from lung cancer might be a potential target for immune checkpoint inhibitor therapy, given its high expression of PD-L1.
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Antígeno B7-H1/análise , Neoplasias Gastrointestinais/secundário , Neoplasias Pulmonares/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Feminino , Trato Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients' antitumor immune response.
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Fatores de Transcrição Forkhead/metabolismo , Linfócitos do Interstício Tumoral/patologia , Neoplasias Epiteliais e Glandulares , Timoma , Neoplasias do Timo , Adolescente , Adulto , Linfócitos B/patologia , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/patologia , Citodiagnóstico , Diagnóstico Diferencial , Humanos , Hiperplasia/patologia , Imuno-Histoquímica , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/patologia , Timoma/diagnóstico , Timoma/patologia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/patologia , Microambiente TumoralRESUMO
AIMS: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). METHODS AND RESULTS: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. CONCLUSION: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.
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Cistadenocarcinoma/genética , Cistadenoma/genética , Papiloma Intraductal/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias das Glândulas Salivares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Cistadenocarcinoma/classificação , Cistadenocarcinoma/diagnóstico , Cistadenocarcinoma/patologia , Cistadenoma/classificação , Cistadenoma/diagnóstico , Cistadenoma/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Papiloma Intraductal/classificação , Papiloma Intraductal/diagnóstico , Papiloma Intraductal/patologia , Neoplasias das Glândulas Salivares/classificação , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologiaRESUMO
We report a case of microsecretory adenocarcinoma of the hard palate. The patient is a 37-year-old woman with a 15 mm submucosal tumor, which was incidentally found by her primary care dentist, in her hard palate. Preoperative magnetic resonance imaging revealed a tumor exhibiting high signal on T2-weighted image, which was gradually enhanced on dynamic study. Histologically, the tumor border was ill-defined without fibrous capsule and adjoined minor salivary gland with permeative infiltration at the tumor periphery. The tumor comprised intercalated duct-like cells with polygonal narrow eosinophilic to clear cytoplasm and small, uniform oval nuclei. These cells formed small infiltrative microcysts, tubules and fascicular cords collecting pale basophilic secretions and small vacuoles setting in an abundant fibromyxoid stroma. The tumor cells were positive for CK AE1+AE3, S-100 protein, and p63, while are completely negative for p40, alpha-SMA, and calponin. The MEF2C-SS18 fusion was identified by reverse transcriptase-polymerase chain reaction followed by Sanger sequencing. The combination of characteristic histology, immunophenotype, and presence of MEF2C-SS18 fusion indicated the diagnosis of microsecretory adenocarcinoma of the hard palate, an entity described only recently. Post-operative course was uneventful and there was no evidence of disease at 4 months after surgery.
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Actinas/genética , Adenocarcinoma/diagnóstico por imagem , Biomarcadores Tumorais/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Neoplasias das Glândulas Salivares/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Feminino , Fusão Gênica , Humanos , Fatores de Transcrição MEF2/genética , Imageamento por Ressonância Magnética , Palato Duro/diagnóstico por imagem , Palato Duro/patologia , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Glândulas Salivares Menores/patologia , Resultado do TratamentoRESUMO
Composite lymphoma is a well-known diagnostic entity exhibiting the synchronous occurrence of two or more distinct types of lymphomas in the same specimen. Here we report two patients, a 14-year-old female (Case 1) and a 45-year-old male (Case 2), with mediastinal composite lymphoma, comprising nodular sclerosis classic Hodgkin lymphoma (NSCHL) and primary mediastinal large B-cell lymphoma (PMBL). Both patients had a mediastinal mass, and manifested two different histologic components in the same biopsy, one characteristic of NSCHL and the other PMBL. The NSCHL areas included Hodgkin and Reed-Sternberg (HRS) cells with typical immunophenotypic features (CD30-positive and CD20-negative), whereas the sheets of large tumor cells characteristic of PMBL were strongly and uniformly CD20-positive. Interestingly, although both cases showed neoplastic PD-L1 (nPD-L1) positivity on the HRS cells of NSCHL, they differed regarding nPD-L1 expression on the PMBL tumor cells. In Case 1, the nPD-L1-negative PMBL component was anatomically situated outside the NSCHL lesion. On the other hand, in Case 2, the nPD-L1-positive PMBL component was characterized by transitional or continuous areas with the NSCHL component. These findings suggested that nPD-L1 expression may define two subtypes of PMBL that are more similar to or distinct from classic Hodgkin lymphoma.
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Antígeno B7-H1/metabolismo , Linfoma Composto/diagnóstico , Doença de Hodgkin/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Neoplasias do Mediastino/diagnóstico , Adolescente , Biomarcadores Tumorais/metabolismo , Feminino , Doença de Hodgkin/metabolismo , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
Although several reports have highlighted neoplastic PD-L1 (nPD-L1) expression in classic Hodgkin lymphoma (CHL), some have addressed associations between its expression and detailed histopathologic features. Here we describe four cases of syncytial variant of CHL (SV-CHL), with and without Epstein-Barr virus (EBV) association, and highlight the diagnostic utility of PD-L1 (clone SP142) immunohistochemistry. The patients were a 61-year-old male, 45-year-old male, 85-year-old female, and 89-year-old female. All presented with cervical or axillary lymphadenopathy, which on biopsy had the established histopathologic features of SV-CHL with a biphasic pattern of cohesive sheets of large tumor cells and typically scattered distribution of Hodgkin and Reed-Stenberg (HRS) cells. These tumor cells showed identical immunophenotypic findings for CD15, CD30, Fascin, PAX5, OCT2, BOB1 and EBV harboring, regardless of location. The exception was absent or decreased expression of nPD-L1 from tumor cells in the confluent sheets, contrasting with HRS cell positivity in typical areas of CHL. These findings offer the first suggestion of possible downregulation of nPD-L1 expression in association with the histopathologic progression of CHL. The results may be relevant for recognizing 'confluent' sheets in the diagnostic workup for SV-CHL.
Assuntos
Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/metabolismo , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Idoso de 80 Anos ou mais , Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified. METHODS: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy. CONCLUSIONS: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.
Assuntos
Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/radioterapia , Intervalo Livre de Doença , Feminino , Humanos , Japão , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Análise Multivariada , Esvaziamento Cervical , Recidiva Local de Neoplasia , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/radioterapia , Neoplasias Parotídeas/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/radioterapia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Accurate diagnosis of invasion depth is important for reliable treatment of esophageal squamous cell carcinoma (ESCC), but it is limited to the muscularis mucosae to slight submucosal invasion (MM/SM1). The diagnostic accuracy of invasion depth is unsatisfactory and remains to be improved. We aimed to investigate the association between the color of the superficial ESCC and invasion depth using linked color imaging (LCI) under light-emitting diode (LED) light sources. METHODS: Lesions diagnosed as superficial ESCC were observed using white light imaging and then by LCI. The color values were calculated using Commission Internationale de l'Eclariage - L*a*b* color space, and the color difference was calculated according to invasion depth. The vascular diameters and vascular angles of the intrapapillary capillary loops were pathologically analyzed. Their correlation with mucosal color was also investigated by LCI. RESULTS: In all, 52 lesions from 48 patients were analyzed. On the basis of invasion depth, the color difference between the normal mucosa and the lesion was larger in the MM/SM1 or deeper group than in the epithelium and the lamina propria mucosa (EP/LPM) group using LCI (P = 0.025). The vascular diameter was positively correlated with the b* color value (correlation coefficient = 0.302, P = 0.033). CONCLUSION: Observation using LCI under LED light sources may improve the endoscopic diagnosis of the invasion depth of superficial ESCC. Further research is needed to validate its usefulness. (UMIN000024615).