Archives of pathology & laboratory medicine最新文献

Context.—: Antibodies to U1 ribonucleoprotein (U1RNP) were first described more than 50 years ago, and although clinically relevant for antinuclear antibody-associated connective tissue disease (ANA-CTD), test results are challenging to interpret.

Objective.—: To evaluate the impact of anti-U1RNP analyte diversity in the assessment of patients at risk for ANA-CTD.

Design.—: Two multiplex assays for U1RNP (Smith [Sm]/RNP and RNP68/A) were used to test serum specimens from consecutive patients (n = 498) under evaluation for CTD in a single academic center. Discrepant specimens were further tested for Sm/RNP antibody by enzyme-linked immunosorbent assay and the BioPlex multiplex assay. Data were evaluated for antibody positivity per analyte and their method of detection, correlations between analytes, and impact on clinical diagnoses through retrospective chart review.

Results.—: Of the 498 patients tested, 47 (9.4%) were positive in the RNP68/A (BioPlex) and 15 (3.0%) were positive in the Sm/RNP (Theradiag) immunoassays. U1RNP-CTD, other ANA-CTD, and no ANA-CTD were diagnosed in 34% (16 of 47), 12.8% (6 of 47), and 53.2% (25 of 47) of the cases, respectively. The prevalence of antibody by method in patients with U1RNP-CTD was 100.0% (16 of 16), 85.7% (12 of 14), 81.5% (13 of 16), and 87.5% (14 of 16) for RNP68/A, Sm/RNP BioPlex, Sm/RNP Theradiag, and Sm/RNP Inova, respectively. For other ANA-CTD and no ANA-CTD, the highest prevalence was observed with RNP68/A; all others had comparable performance.

Conclusions.—: In this study, the overall performance characteristics of Sm/RNP antibody assays were comparable; however, the RNP68/A immunoassay was very sensitive but less specific. In the absence of harmonization, reporting the type of U1RNP analyte in clinical testing may be useful in guiding interpretation and interassay correlations.

Context.—: Differentiated vulvar intraepithelial neoplasia (dVIN) is a human papillomavirus-independent lesion with the potential for rapid progression to invasive squamous cell carcinoma (SCC). The histopathologic features of dVIN are diverse, have overlapping characteristics with lichen sclerosus (LS) and lichen simplex chronicus (LSC), and may be diagnosed by dermatopathologists or gynecologic pathologists because of the vulva's anatomic location.

Objectives.—: To identify the salient histopathologic features of dVIN, particularly those that predict progression to SCC, and to evaluate interobserver agreement in diagnosing dVIN within the same subspecialty and across subspecialties.

Design.—: One general surgical pathologist, 2 pathology-trained dermatopathologists, and 1 gynecologic pathologist blinded to the final diagnoses were asked to record 20 histopathologic features and to provide their final interpretations on cases of dVIN (n = 65), LS (n = 126), LSC (n = 112), and LS with LSC (n = 6).

Results.—: Interobserver agreement for the 4 diagnoses and 10 histopathologic features was moderate. Logistic regression analysis indicated that keratin pearls, basal pleomorphism, and basal layer disarray were independent variables for diagnosing dVIN (coefficients 1.95, 1.97, and 0.91, respectively; P < .001) and progression to SCC (coefficients 1.96, 1.20, and 1.08, respectively; P < .001).

Conclusions.—: There is no single histopathologic feature pathognomonic for dVIN; however, the presence of keratin pearls, basal pleomorphism, and basal layer disarray should raise high suspicion for dVIN and concurrent SCC. Expertise in both dermatologic and gynecologic pathology is beneficial for diagnosing dVIN.

Context.—: Tumoral (grossly visible) intraductal neoplasms of the bile ducts are still being characterized.

Objective.—: To investigate their morphologic, immunohistochemical, and molecular features.

Design.—: Forty-one cases were classified as gastric-, intestinal-, pancreatobiliary-type intraductal papillary neoplasm (IPN), intraductal oncocytic papillary neoplasm (IOPN), or intraductal tubulopapillary neoplasm (ITPN) on the basis of histology. All neoplasms were subjected to targeted next-generation sequencing.

Results.—: The mean age at diagnosis was 69 years (42-81 years); male to female ratio was 1.3. Most neoplasms (n = 23, 56%) were extrahepatic/large (mean size, 4.6 cm). The majority (n = 32, 78%) contained high-grade dysplasia, and 68% (n = 28) revealed invasion. All gastric-type IPNs (n = 9) and most ITPNs/IOPNs showed consistent colabeling for CK7/MUC6, which was less common among others (P = .004). Intestinal-type IPNs (n = 5) showed higher rates of CK20 expression than others (P < .001). Overall, the most commonly mutated genes included TP53 and APC, while copy number variants affected ELF3 and CDKN2A/B. All gastric-type IPNs contained an alteration affecting the Wnt signaling pathway; 7 of 9 (78%) showed aberrations in the MAPK pathway. Mutations in APC and KRAS were common in gastric-type IPNs as compared with others (P = .01 for both). SMAD4 was more frequently mutated in intestinal-type IPNs (P = .02). Pancreatobiliary-type IPNs (n = 14) exhibited frequent alterations in tumor suppressor genes including TP53, CDKN2A/B, and ARID2 (P = .04, P = .01 and P = .002, respectively). Of 6 IOPNs analyzed, 3 (50%) revealed ATP1B1-PRKACB fusion. ITPNs (n = 6) showed relatively few recurrent genetic aberrations. Follow-up information was available for 38 patients (median, 58.5 months). The ratio of disease-related deaths was higher for the cases with invasion (56% versus 10%).

Conclusions.—: Tumoral intraductal neoplasms of the bile ducts, similar to their counterparts in the pancreas, are morphologically and genetically heterogeneous.

Context.—: Low-grade fibromatosis-like metaplastic carcinoma (FLMC) is a very rare subtype of triple-negative metaplastic (spindle cell) breast carcinoma. It is characterized by the proliferation of spindle cells closely resembling fibromatosis, which represents a benign fibroblastic/myofibroblastic breast proliferation. Unlike most triple-negative and basal-like breast cancers, FLMC has a very low potential for metastases, but demonstrates frequent local recurrences.

Objective.—: To genetically characterize FLMC.

Design.—: To this end, we analyzed 7 cases by targeted next-generation sequencing for 315 cancer-related genes and performed comparative microarray copy number analysis in 5 of these cases.

Results.—: All cases shared TERT alterations (6 patients with recurrent c.-124C>T TERT promoter mutation and 1 patient with copy number gain encompassing the TERT locus), had oncogenic PIK3CA/PIK3R1 mutations (activation of the PI3K/AKT/mTOR pathway), and lacked mutations in TP53. TERT was overexpressed in all FLMCs. CDKN2A/B loss or mutation was observed in 4 of 7 cases (57%). Furthermore, tumors displayed chromosomal stability, with only few copy number variations and a low tumor mutational burden.

Conclusions—: We conclude that FLMCs typically show the recurrent TERT promoter mutation c.-124C>T, activation of the PI3K/AKT/mTOR pathway, low genomic instability, and wild-type TP53. In conjunction with previous data of metaplastic (spindle cell) carcinoma with and without fibromatosis-like morphology, FLMC is most likely distinguished by TERT promoter mutation. Thus, our data support the notion of a distinct subgroup within low-grade metaplastic breast cancer with spindle cell morphology and associated TERT mutations.

Context.—: Mesothelioma of the tunica vaginalis testis (TVT) is an extremely rare form of mesothelioma.

Objective.—: To compare the clinical and molecular characteristics of mesothelioma of the TVT with those of mesothelioma at other more common sites, including the relationship with exposure to asbestos.

Design.—: We present clinical and pathological data for 9 cases of primary TVT mesothelioma. We performed whole-genome sequencing on 3 cases for the first time.

Results.—: The majority (7 of 9 cases) of TVT mesotheliomas were epithelioid, with the remaining 2 cases showing biphasic morphology. Morphology and immunohistochemical profiles were indistinguishable from mesothelioma elsewhere. Asbestos exposure was documented for 7 of the 9 cases, with no information for 2 cases. The 3 TVT mesothelioma cases that underwent whole-genome sequencing displayed a mutational profile similar to that of mesothelioma at other sites, including NF2 and TP53 mutations.

Conclusions.—: The clinical and molecular profile of TVT mesothelioma is similar to that of mesothelioma elsewhere.

Context.—: There are no consensus guidelines on submission of pelvic lymph node dissection (PLND) specimens for radical prostatectomies. Complete submission is only performed by a minority of laboratories. Our institution has been following this practice for standard-template and extended-template PLND.

Objective.—: To investigate the utility of total submission of PLND specimens for prostate cancer and understand its impact on patients and the laboratory.

Design.—: Retrospective study examining 733 cases of radical prostatectomies with PLND performed at our institution. Reports and slides with positive lymph nodes (LNs) were reviewed. Data on LN yield, cassette usage, and impact of submission of remaining fat after dissection of grossly identifiable LNs were assessed.

Results.—: Most cases involved submission of extra cassettes for remaining fat (97.5%, n = 697 of 715). Extended PLND yielded a higher mean number of total and positive LNs versus standard PLND (P < .001). However, extended PLND required significantly more cassettes for remaining fat (mean, 8; range, 0-44). There was poor correlation between number of cassettes submitted for PLND with total and positive LN yield and between remaining fat with LN yield. Most positive LNs were grossly identified (88.5%, n = 139 of 157) and were typically larger than those not. Only 4 cases (0.6%, n = 4 of 697) would have been understaged without complete submission of PLND.

Conclusions.—: Total submission of PLND increases detection of metastasis and LN yield yet increases workload significantly with only minimal patient management impact. Hence, we recommend that meticulous gross identification and submission of all LNs be pursued without the need to submit the remaining fat of PLND.

Context.—: Quantitative imaging is a promising tool that is gaining wide use across several areas of pathology. Although there has been increasing adoption of morphologic and immunohistochemical analysis, the adoption of evaluation of fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue has been limited because of complexity and lack of practice guidelines.

Objective.—: To perform human epidermal growth factor receptor 2 (HER2) FISH validation in breast carcinoma in accordance with the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 guideline.

Design.—: Clinical validation of HER2 FISH was performed using the US Food and Drug Administration-approved dual-probe HER2 IQFISH (Dako, Carpinteria, California) with digital scanning performed on a PathFusion (Applied Spectral Imaging, Carlsbad, California) system. Validation parameters evaluated included z-stacking, classifier, accuracy, precision, software, and hardware settings. Finally, we evaluated the performance of digital enumeration on clinical samples in a real-world setting.

Results.—: The accuracy samples showed a final concordance of 95.3% to 100% across HER2 groups 1 to 5. During clinical implementation for HER2 groups 2, 3, and 4, we achieved a final concordance of 76% (95 of 125). Of these cases, only 8% (10 of 125) had discordances with clinical impact that could be identified algorithmically and triaged for manual review.

Conclusions.—: Digital FISH enumeration is a useful tool to improve the efficacy of HER2 FISH enumeration and capture genetic heterogeneity across HER2 signals. Excluding cases with high background or poor image quality and manual review of cases with ASCO/CAP group discordances can further improve the efficiency of digital HER2 FISH enumeration.

Context.—: Immunohistochemistry serves as an ancillary diagnostic tool for a wide variety of neoplastic and nonneoplastic disorders, including infections, workup of inflammatory conditions, and subtyping neoplasms of the pancreas/liver/gastrointestinal luminal tract. In addition, immunohistochemistry is also used to detect a variety of prognostic and predictive molecular biomarkers for carcinomas of the pancreas, liver, and gastrointestinal luminal tract.

Objective.—: To highlight an update on the role of immunohistochemistry in the evaluation of pancreatic/liver/gastrointestinal luminal tract disorders.

Data sources.—: Literature review and authors' research data and personal practice experience were used.

Conclusions.—: Immunohistochemistry is a valuable tool, assisting in the diagnosis of problematic tumors and benign lesions of the pancreas, liver, and gastrointestinal luminal tract, and also in the prediction of prognosis and therapeutic response for carcinomas of the pancreas, liver, and gastrointestinal luminal tract.

Context.—: Salivary gland neoplasms are rare lesions in the head and neck (H&N) pathology realm. There are more than 20 malignant and 15 benign salivary gland neoplasms in the 5th edition of the World Health Organization classification of H&N tumors. These neoplasms consist of heterogeneous groups of uncommon diseases that make diagnosis and treatment challenging for the clinical team. Using an algorithmic immunohistochemical approach-defined tumor origin and type has proven to be effective and advantageous. Immunohistochemistry may be used as sort of a "diagnostic looking glass," not as a positive or negative type tool, but as an indispensable complement to a hematoxylin-eosin morphologic pattern-based approach. Furthermore, the understanding of the novel discoveries of the salivary gland gene fusions and the molecular aspects of these tumors makes the process easier and improve the diagnosis as well as treatment aspects. This review reflects our experience with more recent diagnostic antibodies, which include MYB RNA, Pan-TRK, PLAG1, LEF1, and NR4A3. Each of these is linked with a specific type of neoplasm; for example, gene fusions involving the PLAG1 and HMGA2 oncogenes are specific for benign pleomorphic adenomas, and MYB is associated with adenoid cystic carcinoma.

Objective.—: To review these more recent antibodies, which highly enhance salivary gland neoplasm diagnosis.

Data sources.—: The study sources involved literature PubMed searches, including multiple review articles, case reports, selected book chapters, and Geisinger Medical Center cases.

Conclusions.—: Salivary gland tumors are a rare, varied group of lesions in H&N pathology. We need to have continuous readings and revisions of the molecular consequences of these fusion oncoproteins and their subsequent targets, which will eventually lead to the identification of novel driver genes in salivary gland neoplasms.