Pub Date : 2024-06-27DOI: 10.1007/s12105-024-01653-2
Luvy Delfin, Jan Johannes Doff, Jeffrey Gagan, Allen Flack, Jeffrey F Krane, Vickie Y Jo, Alan G Torell, Doreen Palsgrove, Justin A Bishop
Background: Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested.
Methods: IDCs with pure apocrine morphology, entirely intraductal growth, and no precursor lesion (pleomorphic adenoma or sclerosing polycystic adenoma) were retrieved from the authors' archives. Several immunostains (S100, SOX10, GCDFP-15, AR, p40/SMA) and targeted next generation sequencing (NGS) panel including 1425 cancer-related genes were performed.
Results: Seven entirely IDC with pure apocrine type were collected. The cases arose in the parotid glands (mean, 1.9 cm) of 5 men and 2 women ranging from 51 to 84 years (mean, 69.7 years). Histologically, tumors consisted of rounded to angulated ductal cysts lined by epithelial cells with abundant finely granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Pleomorphism was mild to moderate, the mitotic rate was low, and necrosis was absent. Conventionally invasive foci or areas of intercalated duct-like morphology were not identified. In all cases, luminal cells were diffusely positive for AR and GCDFP-15 while negative for S100/SOX10, and the ducts were completely surrounded by myoepithelial cells highlighted by p40 and SMA. Molecular analysis was successful in 6 cases. Three harbored fusions: one with NCOA4::RET, another with STRN::ALK and one with both CDKN2A::CNTRL and TANC1::YY1AP1. The three fusion-negative cases all harbored HRAS mutations; additional mutations (PIK3CA, SPEN, ATM) were found in 2 of 3 cases. All patients were treated by surgery alone. Six of them are currently free of disease (follow up 12-190 months), but the case harboring NCOA4::RET developed lymph nodes metastasis in the form of a fusion-positive invasive salivary duct carcinoma.
Conclusions: Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no meta
{"title":"Pure Apocrine Intraductal Carcinoma of Salivary Glands: Reassessment of Molecular Underpinnings and Behavior.","authors":"Luvy Delfin, Jan Johannes Doff, Jeffrey Gagan, Allen Flack, Jeffrey F Krane, Vickie Y Jo, Alan G Torell, Doreen Palsgrove, Justin A Bishop","doi":"10.1007/s12105-024-01653-2","DOIUrl":"10.1007/s12105-024-01653-2","url":null,"abstract":"<p><strong>Background: </strong>Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested.</p><p><strong>Methods: </strong>IDCs with pure apocrine morphology, entirely intraductal growth, and no precursor lesion (pleomorphic adenoma or sclerosing polycystic adenoma) were retrieved from the authors' archives. Several immunostains (S100, SOX10, GCDFP-15, AR, p40/SMA) and targeted next generation sequencing (NGS) panel including 1425 cancer-related genes were performed.</p><p><strong>Results: </strong>Seven entirely IDC with pure apocrine type were collected. The cases arose in the parotid glands (mean, 1.9 cm) of 5 men and 2 women ranging from 51 to 84 years (mean, 69.7 years). Histologically, tumors consisted of rounded to angulated ductal cysts lined by epithelial cells with abundant finely granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Pleomorphism was mild to moderate, the mitotic rate was low, and necrosis was absent. Conventionally invasive foci or areas of intercalated duct-like morphology were not identified. In all cases, luminal cells were diffusely positive for AR and GCDFP-15 while negative for S100/SOX10, and the ducts were completely surrounded by myoepithelial cells highlighted by p40 and SMA. Molecular analysis was successful in 6 cases. Three harbored fusions: one with NCOA4::RET, another with STRN::ALK and one with both CDKN2A::CNTRL and TANC1::YY1AP1. The three fusion-negative cases all harbored HRAS mutations; additional mutations (PIK3CA, SPEN, ATM) were found in 2 of 3 cases. All patients were treated by surgery alone. Six of them are currently free of disease (follow up 12-190 months), but the case harboring NCOA4::RET developed lymph nodes metastasis in the form of a fusion-positive invasive salivary duct carcinoma.</p><p><strong>Conclusions: </strong>Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no meta","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1007/s12105-024-01667-w
Ming Liang Oon, Bingcheng Wu, Jian Yuan Goh, Kenneth Tou En Chang, Yan Ling Chong, Zi Wei Wong, Shoo Yi Oh, Charmaine Tan, Min En Nga, Fredrik Petersson
Background: Angiosarcoma is a sarcoma that occurs in a range of tissue types, and only rarely in the salivary glands, showing a predilection for the parotid glands of older patients. Preoperative diagnosis may be challenging, especially on cytology, with significant morphological overlap with high-grade primary salivary gland carcinomas. The molecular alterations of this rare salivary gland neoplasm are also not well-characterized.
Methods and results: We present a case of right submandibular gland swelling in a 73-year-old male. On fine needle aspiration, including immunohistochemical stains on cell block, the tumor was initially diagnosed as poorly differentiated carcinoma. Resection of the submandibular gland revealed epithelioid angiosarcoma. We performed molecular work-up of the tumor, utilizing targeted next-generation sequencing, DNA methylation profiling and fluorescence in-situ hybridization. Histopathologic assessment revealed an infiltrative tumor comprising solid sheets of epithelioid cells. The tumor cells formed haphazardly anastomosing vascular channels with intracytoplasmic lumina containing red blood cells. On immunohistochemistry, the tumor cells were positive for CD31, CD34 and ERG. Approximately 40% of the tumor cells showed nuclear expression of GATA3. A pathogenic TP53 R267W mutation was detected on next-generation sequencing. DNA methylation analysis did not cluster the tumor with any known sarcoma type. Copy number analysis showed possible MYC amplification and CDKN2A losses, although only the latter was confirmed on fluorescence in-situ hybridization.
Conclusion: Epithelioid angiosarcoma is an important differential diagnosis to high-grade salivary gland carcinoma. In particular, GATA3 expression may be encountered in both angiosarcoma and high-grade salivary gland carcinomas and cause diagnostic confusion. Identification of TP53 mutations and CDKN2A losses suggest shared oncogenic pathways with soft tissue angiosarcomas, and should be further investigated.
{"title":"Primary Epithelioid Angiosarcoma of the Submandibular Gland-A Case Report with Histology-Cytology Correlation and Comprehensive Molecular Analysis.","authors":"Ming Liang Oon, Bingcheng Wu, Jian Yuan Goh, Kenneth Tou En Chang, Yan Ling Chong, Zi Wei Wong, Shoo Yi Oh, Charmaine Tan, Min En Nga, Fredrik Petersson","doi":"10.1007/s12105-024-01667-w","DOIUrl":"10.1007/s12105-024-01667-w","url":null,"abstract":"<p><strong>Background: </strong>Angiosarcoma is a sarcoma that occurs in a range of tissue types, and only rarely in the salivary glands, showing a predilection for the parotid glands of older patients. Preoperative diagnosis may be challenging, especially on cytology, with significant morphological overlap with high-grade primary salivary gland carcinomas. The molecular alterations of this rare salivary gland neoplasm are also not well-characterized.</p><p><strong>Methods and results: </strong>We present a case of right submandibular gland swelling in a 73-year-old male. On fine needle aspiration, including immunohistochemical stains on cell block, the tumor was initially diagnosed as poorly differentiated carcinoma. Resection of the submandibular gland revealed epithelioid angiosarcoma. We performed molecular work-up of the tumor, utilizing targeted next-generation sequencing, DNA methylation profiling and fluorescence in-situ hybridization. Histopathologic assessment revealed an infiltrative tumor comprising solid sheets of epithelioid cells. The tumor cells formed haphazardly anastomosing vascular channels with intracytoplasmic lumina containing red blood cells. On immunohistochemistry, the tumor cells were positive for CD31, CD34 and ERG. Approximately 40% of the tumor cells showed nuclear expression of GATA3. A pathogenic TP53 R267W mutation was detected on next-generation sequencing. DNA methylation analysis did not cluster the tumor with any known sarcoma type. Copy number analysis showed possible MYC amplification and CDKN2A losses, although only the latter was confirmed on fluorescence in-situ hybridization.</p><p><strong>Conclusion: </strong>Epithelioid angiosarcoma is an important differential diagnosis to high-grade salivary gland carcinoma. In particular, GATA3 expression may be encountered in both angiosarcoma and high-grade salivary gland carcinomas and cause diagnostic confusion. Identification of TP53 mutations and CDKN2A losses suggest shared oncogenic pathways with soft tissue angiosarcomas, and should be further investigated.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1007/s12105-024-01668-9
Spencer C Roark, Carter T Bruett, Martin G Dominger, Paul D Freedman, Renee F Reich
Malakoplakia is a rare inflammatory disorder which typically occurs in immunocompromised patients secondary to impaired bactericidal activity of macrophages. While this entity commonly arises in the genitourinary and gastrointestinal tracts, lesions of the head and neck have been reported only rarely, with oral cavity involvement reported in 3 cases. The most common presentation of head and neck malakoplakia is that of a cutaneous flesh-colored papule or nodule. This case report, however, illustrates the first time malakoplakia is identified affecting the maxilla and maxillary alveolar ridge mucosa. Histochemical and immunohistochemical stains are presented and include positivity for PAS, von Kossa stain, iron stain, and CD68 and negativity for GMS and Gram stains, indicating an inability to demonstrate microbial infection. Thus, clinicians and pathologists alike should be aware of malakoplakia as a pathologic entity when forming differential diagnoses, particularly in immunosuppressed individuals.
{"title":"Malakoplakia Involving the Maxilla: A Case Report and a Review of the Literature.","authors":"Spencer C Roark, Carter T Bruett, Martin G Dominger, Paul D Freedman, Renee F Reich","doi":"10.1007/s12105-024-01668-9","DOIUrl":"10.1007/s12105-024-01668-9","url":null,"abstract":"<p><p>Malakoplakia is a rare inflammatory disorder which typically occurs in immunocompromised patients secondary to impaired bactericidal activity of macrophages. While this entity commonly arises in the genitourinary and gastrointestinal tracts, lesions of the head and neck have been reported only rarely, with oral cavity involvement reported in 3 cases. The most common presentation of head and neck malakoplakia is that of a cutaneous flesh-colored papule or nodule. This case report, however, illustrates the first time malakoplakia is identified affecting the maxilla and maxillary alveolar ridge mucosa. Histochemical and immunohistochemical stains are presented and include positivity for PAS, von Kossa stain, iron stain, and CD68 and negativity for GMS and Gram stains, indicating an inability to demonstrate microbial infection. Thus, clinicians and pathologists alike should be aware of malakoplakia as a pathologic entity when forming differential diagnoses, particularly in immunosuppressed individuals.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1007/s12105-024-01657-y
Alberto Peraza Labrador, Mikhail Umorin, Madhu Shrestha, Cesar Abad Villacrez, John Wright
Background: Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant syndrome with different skin, lung, and renal manifestations. It is diagnosed commonly in the third decade of life, and patients have an increased risk for pneumothorax and renal carcinomas.
Methods: Articles published in PubMed, and Medline from 1977 to September 2023, were included in the systematic review. Inclusion criteria were applied to case reports, case series, and a retrospective cohort study, describing clinical, histopathological, and genetic findings in patients with BHDS with oral and/or parotid lesions.
Results: Sixteen families/individuals with BHDS were identified for analysis. Patients ranged in age from 20 to 74 years, with an average of 49.4 years. Males were affected 52.2% of the time and females, 39.1%. Skin fibrofolliculomas were reported in 87% of cases, and oral lesions were documented in 47.8%. Parotid tumors were documented in 43.5% of patients, 30.4% of which were oncocytomas, 4.3% bilateral oncocytomas, and 4.3% "oncocytic carcinoma".
Conclusions: Because BHDS is uncommon, its spectrum of clinical manifestations may be underrecognized, especially as the disease is mostly reported at advanced stage. And some of the patients with BHDS may have oncocytic parotid tumors and oral lesions. In this regard, patients presenting these lesions and other indications of BHDS should be considered for renal screening.
{"title":"A Possible Association of Salivary Gland Tumors and Oral Lesions with Birt-Hogg-Dube Syndrome: A Systematic Review.","authors":"Alberto Peraza Labrador, Mikhail Umorin, Madhu Shrestha, Cesar Abad Villacrez, John Wright","doi":"10.1007/s12105-024-01657-y","DOIUrl":"10.1007/s12105-024-01657-y","url":null,"abstract":"<p><strong>Background: </strong>Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant syndrome with different skin, lung, and renal manifestations. It is diagnosed commonly in the third decade of life, and patients have an increased risk for pneumothorax and renal carcinomas.</p><p><strong>Methods: </strong>Articles published in PubMed, and Medline from 1977 to September 2023, were included in the systematic review. Inclusion criteria were applied to case reports, case series, and a retrospective cohort study, describing clinical, histopathological, and genetic findings in patients with BHDS with oral and/or parotid lesions.</p><p><strong>Results: </strong>Sixteen families/individuals with BHDS were identified for analysis. Patients ranged in age from 20 to 74 years, with an average of 49.4 years. Males were affected 52.2% of the time and females, 39.1%. Skin fibrofolliculomas were reported in 87% of cases, and oral lesions were documented in 47.8%. Parotid tumors were documented in 43.5% of patients, 30.4% of which were oncocytomas, 4.3% bilateral oncocytomas, and 4.3% \"oncocytic carcinoma\".</p><p><strong>Conclusions: </strong>Because BHDS is uncommon, its spectrum of clinical manifestations may be underrecognized, especially as the disease is mostly reported at advanced stage. And some of the patients with BHDS may have oncocytic parotid tumors and oral lesions. In this regard, patients presenting these lesions and other indications of BHDS should be considered for renal screening.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1007/s12105-024-01656-z
Mariel Bedell, Dale W Lewis, Raja R Seethala
Background: MYB RNA in situ hybridization (ISH) has emerged as a reliable and accessible marker to support adenoid cystic carcinoma (ACC) diagnosis, though still not well studied. Here, we report our results in a validation and prospective cohort to improve MYB RNA ISH diagnostic accuracy.
Methods: 79 cases (23 retrospective and 56 prospective) underwent MYB RNA ISH testing (44 ACC and 35 non-ACC). MYB RNA ISH results were initially interpreted based on previously established (original) scoring criteria. Weighted "i-scores", percent positive tumor cells, percent tumor cells with large signals (% LS), and staining pattern (abluminal, diffuse, focal non-patterned, or negative) were inputs for logistic regression models. Final model performance characteristics were compared with original scoring criteria and MYB::NFIB FISH results.
Results: An abluminal pattern was characteristic and exclusive to ACC. All i-scores, % LS, and percent positive were significantly higher in ACC. Original scoring criteria yielded a 95.5% sensitivity (Sn), 68.6% specificity (Sp), and 83.5% accuracy. MYB::NFIB FISH yielded a 42.9% sensitivity, 100% specificity, and 60% accuracy. Optimizing for performance, simplicity, and minimal collinearity, our final model was defined as: abluminal pattern and/or % LS > 16.5%, which resulted in a 93.2% Sn, 97.1% Sp, and 94.9% accuracy for ACC diagnosis. False negatives included an ACC with striking tubular eosinophilia and a MYBL1::NFIB translocated ACC. One false positive exclusive to the final model was a nasopharyngeal carcinoma with MYB amplification.
Conclusions: MYB RNA ISH has a higher Sn than MYB::NFIB FISH while retaining high Sp. Our model provides improvements to specificity compared to original scoring criteria and highlight the importance of abluminal staining pattern and % LS. Nonetheless, alternate fusions remain key false negatives while rare non-ACC with other mechanisms of MYB activation may present as false positives.
背景:MYB RNA原位杂交(ISH)已成为支持腺样囊性癌(ACC)诊断的一种可靠、易得的标记物,但研究仍不充分。方法:79 个病例(23 个回顾性病例和 56 个前瞻性病例)接受了 MYB RNA ISH 检测(44 个 ACC 病例和 35 个非 ACC 病例)。MYB RNA ISH 检测结果最初根据以前建立的(原始)评分标准进行解释。加权 "i-分数"、阳性肿瘤细胞百分比、大信号肿瘤细胞百分比(% LS)和染色模式(基底层、弥漫、局灶无模式或阴性)是逻辑回归模型的输入。将最终模型的性能特征与原始评分标准和 MYB::NFIB FISH 结果进行比较:消融模式是 ACC 独有的特征。在 ACC 中,所有 i 分数、LS 百分比和阳性百分比都明显较高。原始评分标准的灵敏度(Sn)为 95.5%,特异度(Sp)为 68.6%,准确率为 83.5%。MYB::NFIB FISH 的灵敏度为 42.9%,特异性为 100%,准确率为 60%。在性能、简便性和最小共线性方面进行优化后,我们的最终模型被定义为:腔隙模式和/或 LS% > 16.5%,从而使 ACC 诊断的灵敏度(Sn)、特异度(Sp)和准确度(Sp)分别达到 93.2%、97.1% 和 94.9%。假阴性包括伴有显著管状嗜酸性粒细胞增多的 ACC 和 MYBL1::NFIB 易位的 ACC。最终模型中只有一个假阳性,即鼻咽癌伴有MYB扩增:结论:与 MYB::NFIB FISH 相比,MYB RNA ISH 的 Sn 值更高,同时保留了较高的 Sp 值。与最初的评分标准相比,我们的模型提高了特异性,并突出了腔内染色模式和LS%的重要性。尽管如此,交替融合仍是关键的假阴性,而罕见的非 ACC 与其他 MYB 激活机制可能会出现假阳性。
{"title":"A Novel Scoring System for MYB RNA In Situ Hybridization Displays High Sensitivity and Specificity for Adenoid Cystic Carcinoma in a Clinical Setting.","authors":"Mariel Bedell, Dale W Lewis, Raja R Seethala","doi":"10.1007/s12105-024-01656-z","DOIUrl":"10.1007/s12105-024-01656-z","url":null,"abstract":"<p><strong>Background: </strong>MYB RNA in situ hybridization (ISH) has emerged as a reliable and accessible marker to support adenoid cystic carcinoma (ACC) diagnosis, though still not well studied. Here, we report our results in a validation and prospective cohort to improve MYB RNA ISH diagnostic accuracy.</p><p><strong>Methods: </strong>79 cases (23 retrospective and 56 prospective) underwent MYB RNA ISH testing (44 ACC and 35 non-ACC). MYB RNA ISH results were initially interpreted based on previously established (original) scoring criteria. Weighted \"i-scores\", percent positive tumor cells, percent tumor cells with large signals (% LS), and staining pattern (abluminal, diffuse, focal non-patterned, or negative) were inputs for logistic regression models. Final model performance characteristics were compared with original scoring criteria and MYB::NFIB FISH results.</p><p><strong>Results: </strong>An abluminal pattern was characteristic and exclusive to ACC. All i-scores, % LS, and percent positive were significantly higher in ACC. Original scoring criteria yielded a 95.5% sensitivity (Sn), 68.6% specificity (Sp), and 83.5% accuracy. MYB::NFIB FISH yielded a 42.9% sensitivity, 100% specificity, and 60% accuracy. Optimizing for performance, simplicity, and minimal collinearity, our final model was defined as: abluminal pattern and/or % LS > 16.5%, which resulted in a 93.2% Sn, 97.1% Sp, and 94.9% accuracy for ACC diagnosis. False negatives included an ACC with striking tubular eosinophilia and a MYBL1::NFIB translocated ACC. One false positive exclusive to the final model was a nasopharyngeal carcinoma with MYB amplification.</p><p><strong>Conclusions: </strong>MYB RNA ISH has a higher Sn than MYB::NFIB FISH while retaining high Sp. Our model provides improvements to specificity compared to original scoring criteria and highlight the importance of abluminal staining pattern and % LS. Nonetheless, alternate fusions remain key false negatives while rare non-ACC with other mechanisms of MYB activation may present as false positives.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1007/s12105-024-01660-3
Leen AlQudah, Trevor Hackman, Amy Brownlee
Mixed neuroendocrine-nonneuroendocrine (MiNEN) neoplasms in the head and neck are exceptionally rare biphasic tumors with unclear pathogenesis and an aggressive clinical behavior. This is the first reported case of an oropharyngeal MiNEN with the nonneuroendocrine component being an HPV-associated adenocarcinoma. The tumor arose in a 56 year-old male with history of long-term cigarette smoking and was composed of an adenocarcinoma intermixed with a small cell neuroendocrine carcinoma. P16 immunohistochemical stain and HPV16/18 in-situ hybridization were strongly and diffusely expressed in both components.
{"title":"Oropharyngeal Mixed Neuroendocrine-Nonneuroendocrine Neoplasm (MiNEN): A Case Report and Literature Review.","authors":"Leen AlQudah, Trevor Hackman, Amy Brownlee","doi":"10.1007/s12105-024-01660-3","DOIUrl":"10.1007/s12105-024-01660-3","url":null,"abstract":"<p><p>Mixed neuroendocrine-nonneuroendocrine (MiNEN) neoplasms in the head and neck are exceptionally rare biphasic tumors with unclear pathogenesis and an aggressive clinical behavior. This is the first reported case of an oropharyngeal MiNEN with the nonneuroendocrine component being an HPV-associated adenocarcinoma. The tumor arose in a 56 year-old male with history of long-term cigarette smoking and was composed of an adenocarcinoma intermixed with a small cell neuroendocrine carcinoma. P16 immunohistochemical stain and HPV16/18 in-situ hybridization were strongly and diffusely expressed in both components.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1007/s12105-024-01659-w
KyuKyu Moe, Hung-Chune Maa, Shih-Tsang Lin, Ying-Ju Kuo
Follicular dendritic cell sarcoma of the parotid gland is an extremely rare tumor, with only six cases reported in the literature. A 51-year-old female had a 3.0 cm tumor resected from the right parotid gland. The tumor exhibited solid sheets, whorls, fascicular pattern, and syncytium appearance with an indistinct cell border. The lymphocytic infiltrate was sprinkled throughout the neoplasm, with focal prominent perivascular cuffing. Immunohistochemically, it was positive for follicular dendritic cell markers CD21, CD23, and CD35. We aim to enhance the understanding of this neoplasm and alert pathologists to this rare entity in this region to avoid misdiagnosis.
{"title":"Follicular Dendritic Cell Sarcoma of the Parotid Gland: A Case Report and Review of Literature.","authors":"KyuKyu Moe, Hung-Chune Maa, Shih-Tsang Lin, Ying-Ju Kuo","doi":"10.1007/s12105-024-01659-w","DOIUrl":"10.1007/s12105-024-01659-w","url":null,"abstract":"<p><p>Follicular dendritic cell sarcoma of the parotid gland is an extremely rare tumor, with only six cases reported in the literature. A 51-year-old female had a 3.0 cm tumor resected from the right parotid gland. The tumor exhibited solid sheets, whorls, fascicular pattern, and syncytium appearance with an indistinct cell border. The lymphocytic infiltrate was sprinkled throughout the neoplasm, with focal prominent perivascular cuffing. Immunohistochemically, it was positive for follicular dendritic cell markers CD21, CD23, and CD35. We aim to enhance the understanding of this neoplasm and alert pathologists to this rare entity in this region to avoid misdiagnosis.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1007/s12105-024-01652-3
José Alcides Almeida de Arruda, João Luiz Gomes Carneiro Monteiro, Maria Eduarda Zeraik Barreto, Mariana Villarroel-Dorrego, Gerardo Gilligan, René Panico, Thayanne Brasil Barbosa Calcia, Shimelly Monteiro de Castro Lara, Alice Maria de Oliveira Silva, Saray Aranda-Romo, Francisco Javier Tejeda-Nava, Mônica Simões Israel, Tarcília Aparecida Silva, Bruno Augusto Benevenuto de Andrade
Background: Uremic stomatitis is often unfamiliar to healthcare professionals. This study presents five cases of uremic stomatitis, providing a comprehensive analysis of their demographic distribution, clinicopathological features, and management strategies based on existing literature.
Methods: Data were collected from centers across Brazil, Argentina, Venezuela, and Mexico. Electronic searches were conducted in five databases supplemented by manual scrutiny and gray literature.
Results: The series consisted of three men and two women with a mean age of 40.2 years. Lesions mostly appeared as white plaques, particularly on the tongue (100%). The median blood urea level was 129 mg/dL. Histopathological analysis revealed epithelial changes, including acanthosis and parakeratosis, with ballooned keratinocytes in the suprabasal region. Oral lesions resolved subsequent to hemodialysis in three cases (75%). Thirty-seven studies comprising 52 cases of uremic stomatitis have been described hitherto. Most patients were male (65.4%) with a mean age of 43.6 years. Clinically, grayish-white plaques (37.3%) and ulcers/ulcerations (28.9%) were common, particularly on the tongue (30.9%). Hemodialysis was performed on 27 individuals. The resolution rate of oral lesions was 53.3%.
Conclusion: Earlier recognition of uremic stomatitis, possibly associated with long-term uremia, holds the potential to improve outcomes for patients with undiagnosed chronic kidney disease.
{"title":"Uremic Stomatitis: A Latin American Case Series and Literature Review.","authors":"José Alcides Almeida de Arruda, João Luiz Gomes Carneiro Monteiro, Maria Eduarda Zeraik Barreto, Mariana Villarroel-Dorrego, Gerardo Gilligan, René Panico, Thayanne Brasil Barbosa Calcia, Shimelly Monteiro de Castro Lara, Alice Maria de Oliveira Silva, Saray Aranda-Romo, Francisco Javier Tejeda-Nava, Mônica Simões Israel, Tarcília Aparecida Silva, Bruno Augusto Benevenuto de Andrade","doi":"10.1007/s12105-024-01652-3","DOIUrl":"10.1007/s12105-024-01652-3","url":null,"abstract":"<p><strong>Background: </strong>Uremic stomatitis is often unfamiliar to healthcare professionals. This study presents five cases of uremic stomatitis, providing a comprehensive analysis of their demographic distribution, clinicopathological features, and management strategies based on existing literature.</p><p><strong>Methods: </strong>Data were collected from centers across Brazil, Argentina, Venezuela, and Mexico. Electronic searches were conducted in five databases supplemented by manual scrutiny and gray literature.</p><p><strong>Results: </strong>The series consisted of three men and two women with a mean age of 40.2 years. Lesions mostly appeared as white plaques, particularly on the tongue (100%). The median blood urea level was 129 mg/dL. Histopathological analysis revealed epithelial changes, including acanthosis and parakeratosis, with ballooned keratinocytes in the suprabasal region. Oral lesions resolved subsequent to hemodialysis in three cases (75%). Thirty-seven studies comprising 52 cases of uremic stomatitis have been described hitherto. Most patients were male (65.4%) with a mean age of 43.6 years. Clinically, grayish-white plaques (37.3%) and ulcers/ulcerations (28.9%) were common, particularly on the tongue (30.9%). Hemodialysis was performed on 27 individuals. The resolution rate of oral lesions was 53.3%.</p><p><strong>Conclusion: </strong>Earlier recognition of uremic stomatitis, possibly associated with long-term uremia, holds the potential to improve outcomes for patients with undiagnosed chronic kidney disease.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-17DOI: 10.1007/s12105-024-01654-1
Lucas Fellipe do Amaral-Sobrinho, Fernanda Silva de Lima, Diego Belmiro do Nascimento Santos, Israel Leal Cavalcante, José Alcides Almeida de Arruda, Juliana de Noronha Santos Netto, Natália Silva Andrade, Bruno Augusto Benevenuto de Andrade, Jefferson R Tenório
Background: Oral lesions of immune-mediated and autoimmune diseases have been well-documented, but studies from Brazil are limited. The varied spectrum of oral lesions within this demographic group poses challenges to clinicians, particularly when they occur in isolation. This study aimed to evaluate the occurrence, clinical characteristics, and management of patients with oral lesions of immune-mediated and autoimmune diseases at a single center in Brazil.
Methods: A retrospective cross-sectional study was conducted from 2010 to 2022. Clinicodemographic data, histopathological features, and treatment modalities were analyzed descriptively and analytically.
Results: Of the 3,790 oral and maxillofacial lesions diagnosed, 160 (4.2%) were confirmed as immune-mediated or autoimmune diseases. The population surveyed predominantly consisted of women (73.7%), with a mean age of 60.2 years. Oral lichen planus (51.3%), mucous membrane pemphigoid (MMP) (23.7%), and pemphigus vulgaris (PV) (19.4%) were the most prevalent lesions. The buccal mucosa (59.4%) was predominantly affected, with pain reported in 46.2% of cases, notably in individuals with PV and MMP. The average time to disease stabilization post-local and/or systemic corticosteroid therapy was 15.8 months for systemic lupus erythematosus, 8.7 months for MMP, and 6.5 months for PV.
Conclusion: Although oral lesions related to immune-mediated and autoimmune diseases are uncommon, their diverse clinicopathological aspects require multidisciplinary management.
{"title":"Oral Lesions of Immune-Mediated and Autoimmune Diseases: A 12-year Experience at a Single Brazilian Referral Center.","authors":"Lucas Fellipe do Amaral-Sobrinho, Fernanda Silva de Lima, Diego Belmiro do Nascimento Santos, Israel Leal Cavalcante, José Alcides Almeida de Arruda, Juliana de Noronha Santos Netto, Natália Silva Andrade, Bruno Augusto Benevenuto de Andrade, Jefferson R Tenório","doi":"10.1007/s12105-024-01654-1","DOIUrl":"10.1007/s12105-024-01654-1","url":null,"abstract":"<p><strong>Background: </strong>Oral lesions of immune-mediated and autoimmune diseases have been well-documented, but studies from Brazil are limited. The varied spectrum of oral lesions within this demographic group poses challenges to clinicians, particularly when they occur in isolation. This study aimed to evaluate the occurrence, clinical characteristics, and management of patients with oral lesions of immune-mediated and autoimmune diseases at a single center in Brazil.</p><p><strong>Methods: </strong>A retrospective cross-sectional study was conducted from 2010 to 2022. Clinicodemographic data, histopathological features, and treatment modalities were analyzed descriptively and analytically.</p><p><strong>Results: </strong>Of the 3,790 oral and maxillofacial lesions diagnosed, 160 (4.2%) were confirmed as immune-mediated or autoimmune diseases. The population surveyed predominantly consisted of women (73.7%), with a mean age of 60.2 years. Oral lichen planus (51.3%), mucous membrane pemphigoid (MMP) (23.7%), and pemphigus vulgaris (PV) (19.4%) were the most prevalent lesions. The buccal mucosa (59.4%) was predominantly affected, with pain reported in 46.2% of cases, notably in individuals with PV and MMP. The average time to disease stabilization post-local and/or systemic corticosteroid therapy was 15.8 months for systemic lupus erythematosus, 8.7 months for MMP, and 6.5 months for PV.</p><p><strong>Conclusion: </strong>Although oral lesions related to immune-mediated and autoimmune diseases are uncommon, their diverse clinicopathological aspects require multidisciplinary management.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11183038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141332287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-17DOI: 10.1007/s12105-024-01641-6
Sinval Vinícius Barbosa do Nascimento, Weslay Rodrigues da Silva, Caroline Augusta Belo Faria, Roberta Karolina Borges de Souza, Carlos Augusto Pereira do Lago, Ana Paula Veras Sobral
Aneurysmal bone cyst is a rare osteolytic lesion of uncertain etiology, commonly observed in the lower limbs, with only 1-2% of reports in gnathic bones. We present the case of a 27-year-old male patient referred to the oral and maxillofacial surgery and traumatology service due to complaints of paresthesia in the mental region and increased mandibular volume. Physical examination revealed midline shift and hard consistency. Imaging examinations demonstrated a radiolucent/hypodense lesion with disruption of the mandibular cortices. The histopathological examination of incisional biopsy material led to the diagnosis of a central giant cell lesion. The patient underwent surgical resection, and the histopathological analysis of the specimen revealed a predominantly solid lesion, characterized by blood-filled spaces of varying size, not covered by epithelium or endothelium, with the presence of spindle cells, multinucleated giant cells, and basophilic osteoid material, concluding the diagnosis of mixed-type aneurysmal bone cyst. Despite being uncommon, aneurysmal bone cysts should be considered in the differential diagnosis of volumetric increase in the gnathic bones of young patients.
{"title":"Aneurysmal Bone Cyst in the Anterior Region of the Mandible.","authors":"Sinval Vinícius Barbosa do Nascimento, Weslay Rodrigues da Silva, Caroline Augusta Belo Faria, Roberta Karolina Borges de Souza, Carlos Augusto Pereira do Lago, Ana Paula Veras Sobral","doi":"10.1007/s12105-024-01641-6","DOIUrl":"10.1007/s12105-024-01641-6","url":null,"abstract":"<p><p>Aneurysmal bone cyst is a rare osteolytic lesion of uncertain etiology, commonly observed in the lower limbs, with only 1-2% of reports in gnathic bones. We present the case of a 27-year-old male patient referred to the oral and maxillofacial surgery and traumatology service due to complaints of paresthesia in the mental region and increased mandibular volume. Physical examination revealed midline shift and hard consistency. Imaging examinations demonstrated a radiolucent/hypodense lesion with disruption of the mandibular cortices. The histopathological examination of incisional biopsy material led to the diagnosis of a central giant cell lesion. The patient underwent surgical resection, and the histopathological analysis of the specimen revealed a predominantly solid lesion, characterized by blood-filled spaces of varying size, not covered by epithelium or endothelium, with the presence of spindle cells, multinucleated giant cells, and basophilic osteoid material, concluding the diagnosis of mixed-type aneurysmal bone cyst. Despite being uncommon, aneurysmal bone cysts should be considered in the differential diagnosis of volumetric increase in the gnathic bones of young patients.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11183029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141332285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}