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Head and Neck Pathology Jun 2024Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated...
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 metastatic potential. With the wide use of RET-and ALK-based targeted therapies, our findings further underscore the importance of fusion analysis for IDC.
Topics: Humans; Male; Middle Aged; Aged; Female; Salivary Gland Neoplasms; Aged, 80 and over; Carcinoma, Intraductal, Noninfiltrating; Biomarkers, Tumor; Adult; Carcinoma, Ductal
PubMed: 38935197
DOI: 10.1007/s12105-024-01653-2 -
Histopathology Jun 2024Low-grade non-intestinal-type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal- and...
AIMS
Low-grade non-intestinal-type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal- and salivary-type neoplasms. Therefore, further characterisation is needed for clearer biological understanding and classification.
METHODS AND RESULTS
Clinical, histological and molecular characterisation of four cases of biphasic, low-grade adenocarcinomas of the sinonasal tract was performed. All patients were male, aged between 48 and 78 years, who presented with polypoid masses in the nasal cavity. Microscopically, virtually all tumours were dominated by tubulo-glandular biphasic patterns, microcystic, focal (micro)papillary, oncocytic or basaloid features. Immunohistochemical staining confirmed biphasic differentiation with an outer layer of myoepithelial cells. Molecular profiling revealed HRAS (p.G13R, p.Q61R) mutations, and concomitant AKT1 (p.E17K, p.Q79R) mutations in two cases. Two cases showed potential in-situ/precursor lesions adjacent to the tumour. Follow-up periods ranged from 1 to 30 months, with one case relapsing locally after 12 and > 20 years.
CONCLUSION
This study further corroborates a distinct biphasic low-grade neoplasm of the sinonasal tract with seromucinous differentiation. Although morphological and molecular features overlap with salivary gland epithelial-myoepithelial carcinoma, several arguments favour categorising these tumours within the spectrum of LGSNAC.
PubMed: 38923026
DOI: 10.1111/his.15251 -
Head and Neck Pathology Jun 2024Birt-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... (Review)
Review
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.
Topics: Humans; Birt-Hogg-Dube Syndrome; Salivary Gland Neoplasms; Middle Aged; Adult; Male; Female; Aged; Young Adult
PubMed: 38896302
DOI: 10.1007/s12105-024-01657-y -
Cureus May 2024Oncocytes are frequently encountered in routine thyroidectomies. The distinction between oncocytic hyperplastic nodules and oncocytic adenomas (OAs) may be challenging....
Oncocytes are frequently encountered in routine thyroidectomies. The distinction between oncocytic hyperplastic nodules and oncocytic adenomas (OAs) may be challenging. Although both entities are benign, a precise diagnosis is essential. We present two cases of solitary oncocytic lesions carrying pathogenic mutations in the p53 and NRAS genes, respectively, leading to a histological diagnosis of oncocytic hyperplastic nodules. Additionally, similar oncocytic nodules from two cases of autoimmune thyroiditis did not show any significant findings on molecular analysis (next-generation sequencing, NGS). Hence, this brief investigative series study is of particular diagnostic interest because it prompts pathologists to use the term adenoma when a solitary oncocytic nodule is encountered, regardless of the established criteria for the diagnosis of adenoma. This viewpoint leads to the possible need for the reevaluation of the histological criteria of adenomas when it comes to oncocytic lesions in order to gain a common diagnostic approach and nomenclature among pathologists and overcome any controversies in such cases.
PubMed: 38882980
DOI: 10.7759/cureus.60361 -
BMJ Case Reports Jun 2024Adrenocortical tumours are rare in children and account for only 0.3%-0.4% of all neoplasms in childhood. They present with variable signs and symptoms, depending on the...
Adrenocortical tumours are rare in children and account for only 0.3%-0.4% of all neoplasms in childhood. They present with variable signs and symptoms, depending on the type of hormonal hypersecretion. The majority of the adrenocortical tumours in children are functional (90%) and malignant (88%). Here, we describe a functional plurihormonal oncocytic adrenal cortical adenoma in a young girl, that mimicked a malignant adrenal lesion, clinically as well as on imaging and biochemical features. This report bears the objective of being aware of the atypical biochemical as well as imaging characteristics of oncocytic adrenal tumours.
Topics: Female; Humans; Adenoma, Oxyphilic; Adrenal Cortex Neoplasms; Adrenocortical Adenoma; Diagnosis, Differential; Tomography, X-Ray Computed; Adolescent
PubMed: 38851224
DOI: 10.1136/bcr-2023-259327 -
The American Journal of Surgical... Jun 2024Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreatobiliary tract are considered a separate entity from intraductal papillary mucinous neoplasms (IPMNs),...
PRKACA/PRKACB Fusions in Pancreatobiliary Intraductal Oncocytic Papillary Neoplasms Including Those With Atypical Morphology: An Analysis of 22 Cases Expanding Morphologic Spectrum.
Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreatobiliary tract are considered a separate entity from intraductal papillary mucinous neoplasms (IPMNs), especially because of the distinct molecular alterations represented by PRKACA or PRKACB fusion. However, IOPNs display a spectrum of cytoarchitectural features. Typically, an IOPN is composed of arborizing papillae lined by layers of cells with oncocytic cytoplasm, prominent nucleoli, and intraepithelial lumina, while a significant subset shows atypical morphology: lack of the characteristic cytoarchitectural features such as arborizing papillae and prominent nucleoli, or mixture with nononcocytic IPMN-like components within a single lesion. To elucidate the tumorigenesis and morphologic spectrum of IOPNs, we analyzed 22 IOPNs, including those with atypical morphology for PRKACA/PRKACB fusions in each different component separately using fluorescence in situ hybridization. In total, 18 of 22 (82%) cases harbored PRKACA/PRKACB fusions, including 3 of 3 (100%) purely typical IOPNs and 15 of 19 (79%) IOPNs with atypical morphology. In the latter, PRKACA/PRKACB fusions were noted in atypical components as well as typical IOPN components. Notably, gastric-type IPMN-like components in the fusion-positive cases were usually low grade and had scattered neoplastic cells with eosinophilic cytoplasm, a morphologic feature suggestive of an early lesion of IOPN. In summary, most IOPNs with atypical morphology either lack characteristic cytoarchitectural features or exhibit a mixture with nononcocytic IPMN-like components, harbored PRKACA/PRKACB fusion as did typical IOPN components. Our observations expanded the morphologic spectrum of IOPNs. They are expected to be useful for correct diagnosis of this neoplasm.
PubMed: 38841868
DOI: 10.1097/PAS.0000000000002259 -
Frontiers in Oncology 2024The pathological features of intraductal oncocytic papillary neoplasm (IOPN) of the bile duct include tumor cells that are rich in eosinophilic cytoplasm and arranged in...
The pathological features of intraductal oncocytic papillary neoplasm (IOPN) of the bile duct include tumor cells that are rich in eosinophilic cytoplasm and arranged in papillary structures. Herein, we report a missed case of IOPN of the bile duct because of concomitant gallstones. A 70-year-old woman was hospitalized with upper abdominal discomfort. The primary diagnosis was choledocholithiasis following imaging examination. However, an unidentified mass was detected after the gallstones were removed. The mass appeared as many papillary protuberances surrounded by fish-egg-like mucosa when viewed by the choledochoscope and was confirmed as IOPN by pathological examination. The patient underwent choledochectomy and no recurrence was observed at the 6-month follow-up examination. In this report, peroral choledochoscopy demonstrated its advantages for the diagnosis of biliary diseases and acquisition of tissue specimens. Therefore, it may solve the challenge related to the lack of preoperative pathological evidence for bile duct tumors.
PubMed: 38841165
DOI: 10.3389/fonc.2024.1349914 -
ESMO Open Jun 2024This phase II nonrandomized study evaluated the efficacy and safety of AZD4635 in combination with durvalumab (Arm A) or durvalumab plus cabazitaxel (Arm B) in patients...
BACKGROUND
This phase II nonrandomized study evaluated the efficacy and safety of AZD4635 in combination with durvalumab (Arm A) or durvalumab plus cabazitaxel (Arm B) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and ≥1 novel hormonal agent.
PATIENTS AND METHODS
The primary endpoint was radiographic progression-free survival (rPFS) per RECIST v1.1 (soft tissue) or the Prostate Cancer Clinical Trials Working Group 3 (bone). Secondary endpoints included safety, tolerability, overall survival, confirmed prostate-specific antigen (PSA) response, pharmacokinetics, and objective response rate. Enrollment in Arm A was stopped following a sponsor decision unrelated to safety. The study was stopped based on the planned futility analysis due to low PSA response in Arm B.
RESULTS
In the final analysis (1 November 2021), 30 patients were treated (Arm A, n = 2; Arm B, n = 28). The median rPFS in Arm B was 5.8 months (95% confidence interval 4.2-not calculable). Median rPFS was 5.8 months versus 4.2 months for patients with high versus low blood-based adenosine signature. The most common treatment-related adverse events in Arm B were nausea (50.0%), diarrhea (46.4%), anemia and neutropenia (both 35.7%), asthenia (32.1%), and vomiting (28.6%). Overall, AZD4635 in combination with durvalumab or AZD4635 in combination with cabazitaxel and durvalumab showed limited efficacy in patients with mCRPC.
CONCLUSIONS
Although the safety profile of both combinations was consistent with known safety data of the individual agents, the results of this trial do not support further development of the combinations.
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Aged; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal; Taxoids; Aged, 80 and over; Progression-Free Survival; Neoplasm Metastasis
PubMed: 38838502
DOI: 10.1016/j.esmoop.2024.103446 -
Cureus Apr 2024The fifth edition of the World Health Organization (WHO) classification introduces new diagnostic methods based on genetic alterations, providing insight into the... (Review)
Review
The fifth edition of the World Health Organization (WHO) classification introduces new diagnostic methods based on genetic alterations, providing insight into the molecular basis of lesions. As a result, the classification system has evolved, new entities have been introduced, and existing entities have been reclassified. Oncocytic lesions of salivary glands are a group of neoplastic conditions characterized by the presence of oncocytic cells. These lesions present a diagnostic challenge due to their overlapping histological features. Therefore, a comprehensive evaluation, including morphological, immunohistochemical, and molecular analysis, is crucial for accurate diagnosis and appropriate management. Accurate classification of salivary gland pathologies is essential for selecting the appropriate treatment methods and predicting outcomes. The introduction of new therapeutic approaches, such as targeted therapies for malignant salivary gland tumors, has improved patient outcomes. However, to effectively implement these therapies in clinical practice, a clear classification of lesions is necessary.
PubMed: 38817461
DOI: 10.7759/cureus.59328 -
Diagnostic Pathology May 2024Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited.
BACKGROUND
Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited.
MATERIALS AND METHODS
To evaluate the diagnostic and prognostic utility of clinicopathological features, morphology, ancillary biomarkers, and reticular histochemistry in adrenocortical neoplasms. We examined 28 adrenocortical carcinomas (ACCs) and 50 adrenocortical adenomas (ACAs) obtained from pathology archives. Clinical data were retrieved from medical records. Two pathologists independently assessed hematoxylin and eosin-stained slides, employing modified Weiss criteria for all tumors and Lin-Weiss-Bisceglia criteria for oncocytic variants. Immunohistochemical markers (Calretinin, alpha-inhibin, MelanA, SF-1, Ki-67, PHH3, IGF-2, β-catenin, P53, CYP11B1, CYP11B2, MLH1, MSH2, MSH6, PMS2, EPCAM) and Gomori's Silver histochemistry were applied. Statistical analysis utilized SPSS Statistics 26.
RESULTS
ACCs exhibited larger tumor sizes (P<0.001) and symptomatic presentations (P = 0.031) compared to ACAs. Parameters of modified Weiss criteria and angioinvasion demonstrated diagnostic value for ACCs. Six immunohistochemical antibodies((MelanA, Ki-67, IGF-2, β-catenin, P53 and CYP11B1) and reticulin framework alterations showed diagnostic value. Notably, Ki-67 and reticulin staining were most recommended. Evident reticulin staining was frequently present in ACCs (P<0.001). Ki-67 was significantly higher in ACCs (P<0.001). Twenty-one conventional and seven oncocytic entities showed different necrosis frequencies. Symptoms and Ki-67 index ≥ 30% were prognostic for ACCs, correlating with shorter survival.
CONCLUSIONS
This study emphasizes the diagnostic value of reticulin framework alterations and a high Ki-67 index. Markers such as CYP11B1, IGF2, P53, β-catenin and MelanA also contribute to the diagnosis of ACCs. Symptoms and Ki-67 index ≥ 30% predict shorter survival. These findings encourges the use of ancillary markers such as reticulin histochemistry and Ki-67 in the workup of evaluations of adrenocortical neoplasms.
Topics: Humans; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Male; Female; Biomarkers, Tumor; Middle Aged; Immunohistochemistry; Adult; Prognosis; Aged; Young Adult; Adolescent; Adrenocortical Adenoma; Child
PubMed: 38802933
DOI: 10.1186/s13000-024-01496-z