-
Modern Pathology : An Official Journal... Apr 2020Recently discovered DNAJB1-PRKACA oncogenic fusions have been considered diagnostic for fibrolamellar hepatocellular carcinoma. In this study, we describe six... (Comparative Study)
Comparative Study
Recently discovered DNAJB1-PRKACA oncogenic fusions have been considered diagnostic for fibrolamellar hepatocellular carcinoma. In this study, we describe six pancreatobiliary neoplasms with PRKACA fusions, five of which harbor the DNAJB1-PRKACA fusion. All neoplasms were subjected to a hybridization capture-based next-generation sequencing assay (MSK-IMPACT), which enables the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving ≥410 genes (n = 6) and/or to a custom targeted, RNA-based panel (MSK-Fusion) that utilizes Archer Anchored Multiplex PCR technology and next-generation sequencing to detect gene fusions in 62 genes (n = 2). Selected neoplasms also underwent FISH analysis, albumin mRNA in-situ hybridization, and arginase-1 immunohistochemical labeling (n = 3). Five neoplasms were pancreatic, and one arose in the intrahepatic bile ducts. All revealed at least focal oncocytic morphology: three cases were diagnosed as intraductal oncocytic papillary neoplasms, and three as intraductal papillary mucinous neoplasms with mixed oncocytic and pancreatobiliary or gastric features. Four cases had an invasive carcinoma component composed of oncocytic cells. Five cases revealed DNAJB1-PRKACA fusions and one revealed an ATP1B1-PRKACA fusion. None of the cases tested were positive for albumin or arginase-1. Our data prove that DNAJB1-PRKACA fusion is neither exclusive nor diagnostic for fibrolamellar hepatocellular carcinoma, and caution should be exercised in diagnosing liver tumors with DNAJB1-PRKACA fusions as fibrolamellar hepatocellular carcinoma, particularly if a pancreatic lesion is present. Moreover, considering DNAJB1-PRKACA fusions lead to upregulated protein kinase activity and that this upregulated protein kinase activity has a significant role in tumorigenesis of fibrolamellar hepatocellular carcinoma, protein kinase inhibition could have therapeutic potential in the treatment of these pancreatobiliary neoplasms as well, once a suitable drug is developed.
Topics: Adult; Aged; Biliary Tract Neoplasms; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; Female; Gene Fusion; Genetic Predisposition to Disease; HSP40 Heat-Shock Proteins; Humans; Liver Neoplasms; Male; Middle Aged; Oxyphil Cells; Pancreatic Neoplasms; Phenotype; Prognosis; Sodium-Potassium-Exchanging ATPase
PubMed: 31676785
DOI: 10.1038/s41379-019-0398-2 -
Nuclear Medicine Review. Central &... 2019Mechanisms that are responsible for positive 99mTc-MIBI uptake in parathyroid glands are not clearly understood, some authors suggest there is a correlation between...
BACKGROUND
Mechanisms that are responsible for positive 99mTc-MIBI uptake in parathyroid glands are not clearly understood, some authors suggest there is a correlation between 99mTc MIBI accumulation and oxyphil cell content or parathyroid gland volume. The aim of our work was to assess the relationship between the pathological structure of parathyroids, their volume, oxyphil cell content and parathyroid 99mTc-MIBI retention.
MATERIAL AND METHODS
A total of 62 hyperfunctioning parathyroid glands in 46 patients were retrospectively analyzed. Preoperative 99mTc-MIBI scintigraphy was performed according to the double-phase and subtraction protocol. After surgery all glands were evaluated histologically, oxyphil cell content was assessed and volume of each excised gland was calculated.
RESULTS
Scintigraphy was positive in 41 of 62 parathyroid glands (66%). The median volume of positive glands was larger than that of negative glands (1.33 ml vs 0.7 ml, p = 0.015). Of the parathyroid lesions, there were 14 (22.6%) cases of nodular hyperplasia, 23 (37.1%) cases of diffuse hyperplasia, and 25 (40.3%) cases of adenomas. A high (≥ 25%) oxyphil cell content was found in 16 glands (25.8%) and a low ( < 25%) oxyphil cell content in 46 (74.2%) glands. Histopathology of parathyroid glands was related to the scintigraphy result (p = 0.002), but not to the 99mTc-MIBI uptake pattern (p = 0.868). The overall result of scintigraphy was not related to the oxyphil cell content (p = 0.797). 99mTc-MIBI uptake pattern wasn't related to the oxyphil cell content (p = 0.833). In general, parathyroid lesions with low oxyphil cell content were larger than parathyroid glands with high oxyphil cell content (1.33 ml vs 0.5 ml, respectively; p = 0.01). The median volume of parathyroids containing a high number of oxyphil cells and having a prolonged 99mTc-MIBI retention was larger than those without prolonged 99mTc-MIBI retention (1.62 ml vs 0.3 ml, respectively; p = 0.008). The median volume of parathyroids with low oxyphil cells content and showing prolonged 99mTc-MIBI retention was larger than those without prolonged 99mTc-MIBI retention (1.95 ml vs 1.07 ml, respectively; p = 0.014).
CONCLUSIONS
Our findings suggest that a positive scintigraphy result depends on parathyroid histopathology and gland volume and does not depend on the presence of oxyphil cells. Prolonged 99mTc-retention is not related to the parathyroid gland histopathology and the presence of oxyphil cells but to the gland volume.
Topics: Female; Humans; Male; Middle Aged; Organ Size; Oxyphil Cells; Parathyroid Glands; Radionuclide Imaging; Retrospective Studies; Technetium Tc 99m Sestamibi
PubMed: 31482540
DOI: 10.5603/NMR.2019.0005 -
Medicine Aug 2019Hybrid oncocytic/chromophobe tumor (HOCT) is defined as tumor composed of renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC). Sporadic HOCT is extremely...
RATIONALE
Hybrid oncocytic/chromophobe tumor (HOCT) is defined as tumor composed of renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC). Sporadic HOCT is extremely rare, the preoperative diagnosis is difficult, and no guidelines for clinical therapy. We report a case who is the youngest male patient of sporadic HOCT in the world, review the previously reported cases, and share the clinical features, diagnosis, treatment, and prognosis of HOCT.
PATIENT CONCERNS
A 30-year-old man was admitted with the complaints of incidental right renal tumor detected by abdominal ultrasound. He had no complaints of urological symptoms, abdominal pain, osphyalgia, and hematuria. Abdominal contrast-enhanced computed tomography revealed an 85 mm × 80 mm × 80 mm unilateral and solid renal mass, and no findings of metastases.
DIAGNOSIS
The preoperative diagnosis was right renal tumor.
INTERVENTIONS
Laparoscopic right radical nephrectomy was performed.
OUTCOMES
Histopathology demonstrated a mixture of cells with the morphologic features of those seen in CHRCC and RO. The patient was final diagnosed as sporadic HOCT. After follow-up of 14 months, the patient had no complaints and evidence of disease recurrence.
LESSONS
Sporadic HOCT is extremely rare. It is possible that core biopsy could improve diagnostic accuracy. Laparoscopic radical nephrectomy or nephron sparing surgery should be considered the clinical therapy of the sporadic HOCT patients. The clinical behavior of HOCT is still entirely uncertain and should be proved by studies with available long follow-up.
Topics: Adenoma, Oxyphilic; Adult; Carcinoma, Renal Cell; Humans; Kidney; Kidney Neoplasms; Male; Nephrectomy; Oxyphil Cells
PubMed: 31415358
DOI: 10.1097/MD.0000000000016641 -
Clinical Kidney Journal Jun 2019Parathyroid glands consist primarily of chief cells. In some cases, the proportion of parathyroid oxyphil cells increases in patients with chronic kidney disease. We...
Parathyroid glands consist primarily of chief cells. In some cases, the proportion of parathyroid oxyphil cells increases in patients with chronic kidney disease. We describe a case of secondary hyperparathyroidism (SHPT) in a patient treated with haemodialysis who initially received large doses of vitamin D and calcium (Ca) supplements, as well as high doses of cinacalcet hydrochloride (C-HCl), but without any effect on parathyroid hormone levels. Following a successful parathyroidectomy, histopathological examination revealed that two of the parathyroid glands consisted of 40% of oxyphil cells. Oxyphil cells have significantly more Ca-sensing receptors (CaSRs) than chief cells, suggesting that CaSRs are involved in the transdifferentiation of chief cells to oxyphil cells. C-HCl treatment leads to a significant increase in parathyroid oxyphil cell content. This case suggests that C-HCl may induce specific phenotypic alterations in hyperplastic parathyroid glands in patients with severe SHPT.
PubMed: 31198545
DOI: 10.1093/ckj/sfy062 -
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 Endocrinological... Nov 2019The aim was to find whether the presence of Hürthle cells (HC) in a smear influences the categorization of FNA results or the risk of malignancy (RoM) of particular...
PURPOSE
The aim was to find whether the presence of Hürthle cells (HC) in a smear influences the categorization of FNA results or the risk of malignancy (RoM) of particular categories of cytological diagnosis.
METHODS
25,220 FNA performed in a single center in years 2005-2017 were analyzed. Almost all the examined patients were exposed to moderate iodine deficiency for most of their lives. The distribution of FNA outcome categories was compared between two groups: with or without HC (HC and non-HC). The RoM was evaluated on the basis of postoperative histopathological examination (3082 patients).
RESULTS
HC were found in 7.5% of diagnostic FNA. HC nodules were classified into categories II (78.2% vs. 91.9%, p < 0.0000) and VI (0.4% vs. 1.2%, p = 0.0017) less often than non-HC nodules, but more frequently to categories III (14.4% vs. 5.8%, p < 0.0000), IV (11.2% vs. 0.9%, p < 0.0000) and V (1.5% vs. 0.8%, p = 0.0013). There were no significant differences in RoM between HC and non-HC nodules. The RoM in HC and non-HC nodules of particular categories of the Bethesda system was as follows: II: 1.8% vs. 0.8%, III: 9.7% vs. 3.8% when only the last FNA was considered and 10.8% vs. 6.4% when the category III in any performed FNA was considered; IV: 12.7% vs. 10.9%; V: 41.7% vs. 58.2%; and VI: 100% vs. 96.9%.
CONCLUSIONS
HC nodules are classified into categories of equivocal cytological outcomes more often than nodules without HC. Nevertheless, the presence of HC in a smear does not significantly affect the RoM of FNA categories.
Topics: Adenocarcinoma, Follicular; Biopsy, Fine-Needle; Cytodiagnosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oxyphil Cells; Prognosis; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule; Thyroidectomy
PubMed: 31077094
DOI: 10.1007/s40618-019-01055-0 -
Ear, Nose, & Throat Journal Jun 2020
Topics: Aged; Cysts; Female; Humans; Laryngeal Diseases; Larynx; Medical Illustration; Oxyphil Cells; Recurrence
PubMed: 30987461
DOI: 10.1177/0145561319840208 -
BMC Systems Biology Apr 2019Identification of Hürthle cell cancers by non-operative fine-needle aspiration biopsy (FNAB) of thyroid nodules is challenging. Resultingly, non-cancerous Hürthle...
BACKGROUND
Identification of Hürthle cell cancers by non-operative fine-needle aspiration biopsy (FNAB) of thyroid nodules is challenging. Resultingly, non-cancerous Hürthle lesions were conventionally distinguished from Hürthle cell cancers by histopathological examination of tissue following surgical resection. Reliance on histopathological evaluation requires patients to undergo surgery to obtain a diagnosis despite most being non-cancerous. It is highly desirable to avoid surgery and to provide accurate classification of benignity versus malignancy from FNAB preoperatively. In our first-generation algorithm, Gene Expression Classifier (GEC), we achieved this goal by using machine learning (ML) on gene expression features. The classifier is sensitive, but not specific due in part to the presence of non-neoplastic benign Hürthle cells in many FNAB.
RESULTS
We sought to overcome this low-specificity limitation by expanding the feature set for ML using next-generation whole transcriptome RNA sequencing and called the improved algorithm the Genomic Sequencing Classifier (GSC). The Hürthle identification leverages mitochondrial expression and we developed novel feature extraction mechanisms to measure chromosomal and genomic level loss-of-heterozygosity (LOH) for the algorithm. Additionally, we developed a multi-layered system of cascading classifiers to sequentially triage Hürthle cell-containing FNAB, including: 1. presence of Hürthle cells, 2. presence of neoplastic Hürthle cells, and 3. presence of benign Hürthle cells. The final Hürthle cell Index utilizes 1048 nuclear and mitochondrial genes; and Hürthle cell Neoplasm Index leverages LOH features as well as 2041 genes. Both indices are Support Vector Machine (SVM) based. The third classifier, the GSC Benign/Suspicious classifier, utilizes 1115 core genes and is an ensemble classifier incorporating 12 individual models.
CONCLUSIONS
The accurate algorithmic depiction of this complex biological system among Hürthle subtypes results in a dramatic improvement of classification performance; specificity among Hürthle cell neoplasms increases from 11.8% with the GEC to 58.8% with the GSC, while maintaining the same sensitivity of 89%.
Topics: Gene Expression Profiling; Genomics; Heterozygote; Humans; Machine Learning; Mitochondria; Neoplasms; Oxyphil Cells; Sequence Analysis
PubMed: 30952205
DOI: 10.1186/s12918-019-0693-z -
World Journal of Surgery Jun 2019The inability to identify the pathological gland at surgery results in failure to cure hyperparathyroidism in 2-5%. The poorly understood characteristic of parathyroid...
BACKGROUND
The inability to identify the pathological gland at surgery results in failure to cure hyperparathyroidism in 2-5%. The poorly understood characteristic of parathyroid tissue to manifest autofluorescence (AF) under near-infrared (NIR) light has been promoted as an intraoperative adjunct in parathyroid surgery. This study sought to explore potential clinical correlates for AF and assess the clinical utility of AF in parathyroid surgery.
METHODS
Consecutive patients undergoing parathyroid surgery for primary and renal disease were included. NIR imaging was used intraoperatively and the degree of AF of parathyroid glands graded by the operating surgeon. Variables assessed for correlation with AF were: pre-operative serum calcium and PTH, SestaMIBI positivity, gland weight and histological composition.
RESULTS
Ninety-six patients underwent parathyroidectomy over an 8-month period: 49 bilateral explorations, 41 unilateral and 6 focussed lateral approaches: 284 potentially 'visualisable' glands in total. Two hundred and fifty-seven glands (90.5%) were visualised with NIR. Correlation was found between the degree of fluorescence and pre-operative serum calcium and PTH, but not between gland weight and SestaMIBI positivity. In those with renal hyperparathyroidism, a predominance of oxyphil cells correlated with increased AF.
CONCLUSION
Autofluorescence intensity correlates with serum calcium, PTH and gland composition. Further refinements would be required for this information to be of value in a clinical setting. Improvements allowing NIR to visualise the additional 9.5% of parathyroids and overcome the variation in signal intensity due to depth of access are required for the routine adoption of this technology. At present, its routine use in a clinical setting cannot be justified.
Topics: Adult; Aged; Aged, 80 and over; Calcium; Female; Fluorescence; Humans; Intraoperative Care; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Prospective Studies; Reproducibility of Results; Spectroscopy, Near-Infrared; Young Adult
PubMed: 30737552
DOI: 10.1007/s00268-019-04929-9 -
Cancer Cytopathology Mar 2019Hürthle cell-rich nodules (HCNs) encompass non-neoplastic to malignant lesions. There is paucity of literature on the frequency distribution of HCNs among Bethesda...
BACKGROUND
Hürthle cell-rich nodules (HCNs) encompass non-neoplastic to malignant lesions. There is paucity of literature on the frequency distribution of HCNs among Bethesda categories, histologic follow-up, risk of malignancy (ROM), and risk of neoplasia (RON). The objective of this retrospective, multi-institutional study was to determine the prevalence of the cytologic diagnostic category and surgical outcomes of patients with HCN.
METHODS
Nine tertiary health centers representing 6 Asian countries participated. Cases were retrieved from respective databases. The Bethesda System for Reporting Thyroid Cytopathology was used. Cytology results were correlated with surgical diagnoses.
RESULTS
Of 42,190 thyroid aspirates retrieved, 760 (1.8%) had a Hürthle cell predominance. Most (61%) were categorized as atypia of undetermined significance/follicular lesion of undetermined significance, Hürthle cell type" (AUS-H); 35% were categorized as follicular neoplasm, Hürthle cell type (FN-H); and 4% were categorized as suspicious for malignancy (SFM). Histologic follow-up was available for 288 aspirates (38%). Most were benign on resection (66%), and the most common histologic diagnosis was Hürthle cell adenoma (28.5%). The ROM for AUS-H, FN-H, and SFM, as calculated on resected nodules, was 32%, 31%, and 71%, respectively; and the RON was 47%, 81%, and 77%, respectively. The 5 institutions that had an AUS-H:HCN ratio below 0.5 diagnosed HCN less frequently as AUS-H than as FN-H.
CONCLUSIONS
This is the largest, contemporary, multi-institutional series of HCNs with surgical follow-up. Although there was wide interinstitutional variation in prevalence and surgical outcomes, there was no significant difference in the ROM among institutions. The categories AUS-H and FN-H had a similar ROM for resected nodules.
Topics: Adenoma, Oxyphilic; Adolescent; Adult; Asia; Biopsy, Fine-Needle; Cytodiagnosis; Female; Humans; Male; Outcome Assessment, Health Care; Oxyphil Cells; Prevalence; Retrospective Studies; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule
PubMed: 30668897
DOI: 10.1002/cncy.22101