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International Journal of Molecular... Aug 2020The intraductal oncocytic papillary neoplasm (IOPN) of the pancreas has been recognized by WHO classification as a unique intraductal papillary mucinous neoplasm (IPMN)...
The intraductal oncocytic papillary neoplasm (IOPN) of the pancreas has been recognized by WHO classification as a unique intraductal papillary mucinous neoplasm (IPMN) category. IOPN is composed of oxyphil cells, usually expressing MUC5AC, MUC6, and Hep Par-1, and harboring / fusion genes as their genetic hallmark. Although IOPNs are associated with an infiltrative adenocarcinoma in up to 30% of cases, the survival rate after surgical resection approaches 100%. This highlights the importance of the correct IOPN diagnosis, above all in cases with an associated invasive component. In this study, the immunohistochemical expression of CD117 was investigated in 111 IPMNs, including 17 oncocytic, 45 gastric, 20 pancreatico-biliary, and 29 intestinal IPMNs. We also tested the expression of MUC5AC, MUC6, and Hep Par-1 in the IOPN cohort. CD117 positivity was significantly more frequent in IOPNs compared to the other IPMN subtypes ( < 0.0001). Furthermore, within IOPN, a lower or absent CD117, MUC5AC, MUC6, and Hep Par-1 expression tended to be associated with the presence of an infiltrative component. Our findings shed light into the biology of these complex lesions, which are confirmed to be a distinctive IPMN subtype; notably, CD117 emerged as a potential, additional tool in the differential diagnosis of IPMNs.
Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Carcinoma, Papillary; Cell Line, Tumor; Cohort Studies; Humans; Mucins; Oxyphil Cells; Pancreatic Intraductal Neoplasms; Proto-Oncogene Proteins c-kit
PubMed: 32806726
DOI: 10.3390/ijms21165794 -
International Journal of Clinical and... 2011Histologic and immunohistochemical features of oncocytic papillary renal cell carcinoma (RCC) have not been fully elucidated. The author herein report a case of...
Histologic and immunohistochemical features of oncocytic papillary renal cell carcinoma (RCC) have not been fully elucidated. The author herein report a case of oncocytic papillary RCC (OPRCC). A 71-year-old man with diabetes mellitus and diabetic nephropathy was found to have a small right renal tumor by CT. He had been treated with hemodialysis for chronic renal failure for 10 years. A nephrectomy was performed. Grossly, a small (1.5cm) encapsulated yellow tumor was found in the kidney. Histologically, the tumor was completely encapsulated, and consisted entirely of atypical oncocytes arranged in a diffuse papillary structure with fibrovascular cores. The oncocytes showed grade 3 atypia and pseudostratification. A few mitotic figures were seen, and psammoma bodies, foamy macrophages, and hemosiderin were scattered. Histochemically, the tumor cells were positive for colloidal iron, and negative for mucins (Alcian blue/PAS). Immunohistochemical results of the tumor were as follows: α-methylacyl-coenzyme A rasemase (AMACR) +++, vimentin +++, cytokeratin (CK) 18 +++, CD10 +++, S-100 protein +, MUC1 ++, MUC2 ++, MUC5AC ++, MUC6 ++, panCK Cam5.2 +, CK7 +, CK8 +, CK14 +, CK19 +, CK20 +, p53 +, HepPar1 +, CD68 +, platelet-derived growth factor-α (PDGFRA) +, PanCK AE1/3 -, PanCK WSS -, PanCK MNF115 -, CK 35BE12 -, CK5/6 -, EMA -, desmin -, smooth muscle antigen -, α-fetoprotein -, CEA -, estrogen receptor -, progesterone receptor -, HER2 -, p63 -, and KIT -. Ki67 labeling was 6%. These results suggest that OPRCC can express colloidal iron, low molecular weight CKs, S100 protein, MUC1, MUC2, MUC5AC, MUC6, p53, PDGFRA, and HepPar1.
Topics: Aged; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Renal Cell; Diabetic Nephropathies; Humans; Immunohistochemistry; Kidney Neoplasms; Male; Nephrectomy; Oxyphil Cells; Renal Dialysis
PubMed: 22076171
DOI: No ID Found -
Modern Pathology : An Official Journal... Sep 2016In 2010, the World Health Organization reclassified the entity originally described as intraductal oncocytic papillary neoplasm as the 'oncocytic subtype' of intraductal...
In 2010, the World Health Organization reclassified the entity originally described as intraductal oncocytic papillary neoplasm as the 'oncocytic subtype' of intraductal papillary mucinous neoplasm. Although several key molecular alterations of other intraductal papillary mucinous neoplasm subtypes have been discovered, including common mutations in KRAS, GNAS, and RNF3, those of oncocytic subtype have not been well characterized. We analyzed 11 pancreatic 'oncocytic subtype' of intraductal papillary mucinous neoplasms. Nine pancreatic 'oncocytic subtype' of intraductal papillary mucinous neoplasms uniformly exhibited typical entity-defining morphology of arborizing papillae lined by layers of cells with oncocytic cytoplasm, prominent, nucleoli, and intraepithelial lumina. The remaining two were atypical. One lacked the arborizing papilla and had flat oncocytic epithelium only; the other one had focal oncocytic epithelium in a background of predominantly intestinal subtype intraductal papillary mucinous neoplasm. Different components of this case were analyzed separately. Formalin-fixed, paraffin-embedded specimens of all cases were microdissected and subjected to high-depth-targeted next-generation sequencing for a panel of 300 key cancer-associated genes in a platform that enabled the identification of sequence mutations, copy number alterations, and select structural rearrangements involving all targeted genes. Fresh frozen specimens of two cases were also subjected to whole-genome sequencing. For the nine typical pancreatic 'oncocytic subtype' of intraductal papillary mucinous neoplasms, the number of mutations per case, identified by next-generation sequencing, ranged from 1 to 10 (median=4). None of these cases had KRAS or GNAS mutations and only one had both RNF43 and PIK3R1 mutations. ARHGAP26, ASXL1, EPHA8, and ERBB4 genes were somatically altered in more than one of these typical 'oncocytic subtype' of intraductal papillary mucinous neoplasms but not in the other two atypical ones. In the neoplasm with flat oncocytic epithelium, the only mutated gene was KRAS. All components of the intestinal subtype intraductal papillary mucinous neoplasms with focal oncocytic epithelium manifested TP53, GNAS, and RNF43 mutations. In conclusion, this study elucidates that 'oncocytic subtype' of intraductal papillary mucinous neoplasm is not only morphologically distinct but also genetically distinct from other intraductal papillary mucinous neoplasm subtypes. Considering that now its biologic behavior is also being found to be different than other intraductal papillary mucinous neoplasm subtypes, 'oncocytic subtype' of intraductal papillary mucinous neoplasm warrants being recognized separately.
Topics: Biomarkers, Tumor; Chromogranins; DNA Mutational Analysis; DNA-Binding Proteins; Female; GTP-Binding Protein alpha Subunits, Gs; Gene Expression Profiling; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Male; Middle Aged; Mutation; Neoplasms, Cystic, Mucinous, and Serous; Oncogene Proteins; Oxyphil Cells; Pancreatic Neoplasms; Phenotype; Proto-Oncogene Proteins p21(ras); Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases; Whole Genome Sequencing
PubMed: 27282351
DOI: 10.1038/modpathol.2016.98 -
Cancer Cytopathology Jun 2019Salivary gland neoplasm of uncertain malignant potential (SUMP) is a diagnostic category in the Milan System for Reporting Salivary Gland Cytopathology. The objective of...
Risk of malignancy associated with cytomorphology subtypes in the salivary gland neoplasm of uncertain malignant potential (SUMP) category in the Milan System: A bi-institutional study.
BACKGROUND
Salivary gland neoplasm of uncertain malignant potential (SUMP) is a diagnostic category in the Milan System for Reporting Salivary Gland Cytopathology. The objective of this study was to assess the risk of neoplasm (RON) and the risk of malignancy (ROM) in SUMP cases by evaluating them based on their prominent cytomorphology.
METHODS
The pathology databases were searched for cases of fine-needle aspiration-diagnosed SUMP at The Johns Hopkins Hospital and Northwestern University from 2013 to 2018. Only cytopathology cases diagnosed as SUMP that had available surgical follow-up were included.
RESULTS
Sixty-five patients with SUMP were identified, including 31 men and 34 women who ranged in age from 15 to 87 years (mean age, 55.2 years). Sixty-five cases had histologic follow-up, including 13 (20%) with basaloid features, 13 (20%) with oncocytic features, and 39 (60%) with unspecified features. No cases with clear cell features were found. Overall, the RON in the SUMP category was 95.4% (62 of 65 cases), and the ROM was 33.8% (22 of 65 cases). The RON in SUMPs with basaloid, oncocytic, and unspecified subtypes was 92.3%, 100%, and 94.9%, respectively, whereas the ROM was 38.5%, 7.7%, and 41%, respectively. The most common benign neoplasm was pleomorphic adenoma (23.1%), whereas mucoepidermoid carcinoma (9.2%) was the most common malignant neoplasm.
CONCLUSIONS
This study shows that the ROM differs significantly based on cytomorphology subtypes, whereas the overall ROM is approximately the same as the target rate in the Milan System for Reporting Salivary Gland Cytopathology. Moreover, the RON remains high in the SUMP category among different cytomorphology subtypes. Adequate sampling, immunohistochemical staining, and familiarity with metaplastic and reactive changes may improve the diagnosis.
Topics: Adenoma, Pleomorphic; Adolescent; Adult; Aged; Aged, 80 and over; Biopsy, Fine-Needle; Carcinoma, Mucoepidermoid; Databases, Factual; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oxyphil Cells; Retrospective Studies; Risk Assessment; Salivary Gland Neoplasms; Salivary Glands; Young Adult
PubMed: 31116514
DOI: 10.1002/cncy.22150 -
Journal of Pathology and Translational... Sep 2015We report a rare case of oncocytic renal cell carcinoma (RCC) with tubulopapillary growth in the background of tuberculous end-stage kidney disease. Histology of the...
We report a rare case of oncocytic renal cell carcinoma (RCC) with tubulopapillary growth in the background of tuberculous end-stage kidney disease. Histology of the renal mass consisted of oncocytic cells forming solid, thin tubules and rare papillae. The tumor had abundant eosinophilic oncocytic cells containing occasional cytoplasmic Mallory body-like hyaline globules and a tiny focus of clear cells with intervening mature fat. Both the oncocytic cells and clear cells were immunoreactive for a-methylacyl-CoA racemase, vimentin, pancytokeratin, and CD10, and negative for transcription factor E3, CD15, human melanoma black 45, and c-kit. Mallory body-like hyaline globules were positive for CAM 5.2 and periodic acid-Schiff with or without diastase. Ultrastructurally, the tumor cells had abundant cytoplasmic mitochondria. The present case is a rare case of oncocytic RCC with tubulopapillary growth pattern. The case is unique in that the tumor was mixed with fat component, which is not common in RCC and thus can lead to misdiagnosis.
PubMed: 26265689
DOI: 10.4132/jptm.2015.07.01 -
Archives of Pathology & Laboratory... Feb 2004We report an unusual case of biliary cystadenocarcinoma with oncocytic differentiation. The patient was a 43-year-old woman who presented with right upper quadrant pain.... (Review)
Review
We report an unusual case of biliary cystadenocarcinoma with oncocytic differentiation. The patient was a 43-year-old woman who presented with right upper quadrant pain. Imaging revealed a 16 x 10 x 10-cm, heterogenous, right hepatic mass with extension into the right atrium. Surgical resection revealed a papillary neoplasm of malignant cells with atypical hyperchromatic nuclei and prominent nucleoli lining fibrovascular cores. Mesenchymal stroma was not present. The majority of the epithelial cells had abundant eosinophilic granular cytoplasm, consistent with oncocytic differentiation. There was extensive stromal and hepatic parenchymal invasion. Immunohistochemical staining revealed a "biliary pattern" of cytokeratin subset immunoreactivity, with positivity for cytokeratin 7 and an absence of staining with cytokeratin 20. The tumor was negative for mucin, carcinoembryonic antigen, alpha-fetoprotein, calretinin, CD31, and chromogranin. There was granular cytoplasmic staining with phosphotungstic acid hematoxylin, consistent with the presence of abundant mitochondria. Electron microscopy revealed abundant mitochondria within the neoplastic cells. This case is quite unusual because female patients only rarely lack the characteristic ovarian-like mesenchymal stroma of biliary cystadenomas/cystadenocarcinomas. Furthermore, to our knowledge, oncocytic differentiation in this neoplasm has been reported previously on only 2 occasions. The biologic behavior and prognostic significance, if any, of the lack of mesenchymal stroma in female patients or the presence of oncocytic differentiation remains to be further elucidated as more of these cases are described.
Topics: Adult; Biliary Tract Neoplasms; Cell Differentiation; Cystadenocarcinoma; Female; Histocytochemistry; Humans; Mitochondria; Oxyphil Cells
PubMed: 14736268
DOI: 10.5858/2004-128-e25-OBCACR -
Journal of Clinical Pathology Oct 2006The introduction of preoperative chemoradiation into the treatment protocol of rectal adenocarcinomas has affected the microscopical morphology in subsequent resection...
BACKGROUND
The introduction of preoperative chemoradiation into the treatment protocol of rectal adenocarcinomas has affected the microscopical morphology in subsequent resection specimens. The constellation of histopathological changes is varied and well documented.
AIM
To describe oncocytic change in rectal cancers that have been treated with chemoradiation before surgery.
METHODS
7 of 54 patients with rectal cancer were identified with a history of chemoradiation, specifically directed to the rectal tumours in fractions of 4500-5000 cGy of radiation and 5-fluorouracil. The rectal tumours in five of these seven patients were composed of oncocytes that constituted 30-80% of the cancers. The patients were three men and two women aged 65-73 years, all with T3 N0 tumours. The intervals between chemoradiation and resection varied from 3 to 12 weeks.
RESULTS
The tumour cells conformed to oncocytes morphologically (large size with abundant, granular eosinophilic cytoplasm, vesicular nuclei and prominent acidophilic nucleoli), immunohistochemically (positive for carcinoembryonic antigen, cytokeratin 20 and caudal type homeo box transcription factor 2, but negative for both chromogranin and synaptophysin) and ultrastructurally (large cells showing tight junctions, cytoplasmic engorgement by mitochondria and absence of neurosecretory granules).
CONCLUSIONS
The changes in these cells differ from those described previously in endocrine cells encountered in pretreated rectal cancers. Oncocytic change in this particular clinical context occurs as a reflection of cytotoxic damage or cellular hypoxia induced by chemoradiation resulting in degeneration of the cell and the oncocytic phenotype. Oncocytic change may be an under-recognised histopathological change in rectal cancers receiving preoperative chemoradiation.
Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Chemotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Male; Neoadjuvant Therapy; Oxyphil Cells; Radiotherapy, Adjuvant; Rectal Neoplasms
PubMed: 16467161
DOI: 10.1136/jcp.2005.031997 -
PloS One Nov 2009Oncocytes of the thyroid gland (Hürthle cells) are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular...
BACKGROUND
Oncocytes of the thyroid gland (Hürthle cells) are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown.
METHODOLOGY/PRINCIPAL FINDINGS
Using transgenic mice chronically expressing IFNgamma in thyroid gland, we showed changes in the thyroid follicular epithelium reminiscent of the human oncocyte. Transcriptome analysis comparing transgenic to wild type thyrocytes revealed increased levels of immunoproteasome subunits like LMP2 in transgenics, suggesting an important role of the immunoproteasome in oncocyte pathogenesis. Pharmacologic blockade of the proteasome, in fact, ameliorated the oncocytic phenotype. Genetic deletion of LMP2 subunit prevented the development of the oncocytic phenotype and primary hypothyroidism. LMP2 was also found expressed in oncocytes from patients with Hashimoto thyroiditis and Hürthle cell tumors.
CONCLUSIONS/SIGNIFICANCE
In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism.
Topics: Adenoma, Oxyphilic; Animals; Cell Nucleus; Female; Gene Expression Regulation; Hashimoto Disease; Humans; Hypothyroidism; Immune System; Interferon-gamma; Mice; Mice, Inbred C57BL; Mice, Transgenic; Oxyphil Cells; Phenotype; Proteasome Endopeptidase Complex; Thyroid Gland
PubMed: 19924240
DOI: 10.1371/journal.pone.0007857 -
Medicine Sep 2016Oncocytic carcinoma (OC) arising in the submandibular gland is an unusual malignant neoplasm, with <20 cases previously reported. The cancer is characterized by numerous...
BACKGROUND
Oncocytic carcinoma (OC) arising in the submandibular gland is an unusual malignant neoplasm, with <20 cases previously reported. The cancer is characterized by numerous morphologically abnormal mitochondria present in the cytoplasm and marked cellular pleomorphism. At its most severe, the tumor may invade into the surrounding tissues, including intravascular, lymphatic, or perineural invasion, and lead to regional nodal or distant metastasis.
METHODS
The current study describes a novel OC case in a 46-year-old male, the youngest case of the review. The patient presented with a 5-month history of an intermittently painful mass.
RESULTS
Following magnetic resonance imaging, excisional biopsy, hematoxylin-eosin staining, phosphotungstic acid-hematoxylin staining, and immunohistochemical examination, an OC of the submandibular gland was diagnosed.
CONCLUSION
The current study summarizes the pathogenesis, diagnosis, therapeutics, and the prognosis of OC. The literature review regarding this rare disease is also presented to emphasize the lack of specific markers of OC and the risk of cervical lymph metastasis.
Topics: Adult; Carcinoma; Humans; Male; Oxyphil Cells; Submandibular Gland; Submandibular Gland Neoplasms
PubMed: 27631263
DOI: 10.1097/MD.0000000000004897 -
Hormones (Athens, Greece) 2006
Review
Topics: Adenoma, Oxyphilic; Algorithms; Biopsy, Fine-Needle; Calcitonin; Humans; Oxyphil Cells; Palpation; Thyroid Nodule
PubMed: 16950751
DOI: 10.14310/horm.2002.11188