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Dysgerminoma of the Ovary: An Analysis of 140 Cases Emphasizing Unusual Microscopic Findings and Resultant Diagnostic Problems
Warnnissorn, Malee MD; Watkins, Jaclyn C. MD, MS; Young, Robert H. MD
doi : 10.1097/PAS.0000000000001687
August 2021 - Volume 45 - Issue 8 - p 1009-1027
One-hundred fourty pure dysgerminomas were evaluated with particular focus on the microscopic features as seen in 125 cases with available slides. The patients ranged from 8 to 59 years of age (mean, 24.1?y). The tumors, bilateral in 4% of the cases and with a mean tumor diameter of 13 cm, were typically soft, lobulated, homogeneous, and creamy white to tan to yellow but necrosis was found in 13%, hemorrhage in 20%, and focal cystic change in 15%. On microscopic examination, the patterns and other notable features encountered, including their frequency, were as follows: an alveolar pattern resulting from delicate fibrovascular septa (51%), diffuse (33%), macronodular (14%), insular (26%), cords (28%), solid tubular (17%), microspaces (sometimes simulating glands) (12%), follicle-like spaces (5%), prominent fibrous bands (65%), stromal edema (56%), stromal luteinization (9%), granulomatous infiltrate (46%), lymphocytic infiltrate (100%), Langhans cell type giant cells (35%), syncytiotrophoblast giant cells (6%), prominent population of cells with pale to clear cytoplasm (73%), cells with amphophilic to eosinophilic cytoplasm (53%) and vacuolated occasionally signet ring-like cells (7%). Various constellations of the above findings often resulted in an appearance different from that usually portrayed in the literature and certain tumors of very different nature being in the differential such as undifferentiated carcinoma not otherwise specified, small cell carcinoma of hypercalcemic type, and malignant lymphoma. The correct diagnosis can be arrived at by considering the usual relative youth of the patient, often rather characteristic gross features, and most crucially careful attention to the microscopic features and awareness of variant morphologic findings. Those that are particularly problematic based on this study are diffuse growth with inconspicuous fibrovascular septa, macronodules, cords, solid tubular formations, spaces ranging from small to large, and mimicking glands or follicles, prominent fibrous to edematous stroma, and cells with amphophilic to eosinophilic cytoplasm. According to the degree of difficulty and confidence of the interpreter, well-known immunohistochemical features of dysgerminoma, which largely differ from those of other neoplasms in the differential, will aid if felt indicated.
Mucoacinar Carcinoma: A Rare Variant of Mucoepidermoid Carcinoma
Bundele, Manish MBBS*; Weinreb, Ilan MD†; Xu, Bin MD‡; Chiosea, Simion MD§; Faquin, William MD, PhD?; Dias-Santagata, Dora PhD?; Leon, Marino MD¶; Hyrcza, Martin MD, PhD#; Seethala, Raja R. MD§
doi : 10.1097/PAS.0000000000001752
August 2021 - Volume 45 - Issue 8 - p 1028-1037
Mucoepidermoid carcinoma (MEC) is generally characterized by an admixture of mucous, epidermoid and intermediate type cells. Numerous variants morphologies are described and defined by stromal and/or cytoplasmic tinctorial characteristics. We now report 11 cases of MEC with serous acinar differentiation, reflecting a distal intercalated duct/acinar phenotype, which we designate as mucoacinar carcinomas. Seven patients were female while 4 were male with a mean age of 55 years (range: 21 to 72?y). Ten cases were from the parotid while 1 was from the submandibular gland. Mean size of the tumors was 1.8?cm (range: 0.7 to 4.5?cm). Three cases were low grade, 7 were intermediate grade, and 1 was high grade. Low to intermediate grade cases demonstrated prominent clear to vacuolated cells with focal serous acinar differentiation. The high-grade case showed a distinctive scattering of acinar cells interspersed between epidermoid cells. Periodic acid Schiff after diastase (9/9), SOX-10 (9/9), and DOG-1 (9/10) highlighted the acinar component. Six of 7 cases showed a focal acinar predominant NR4A3 expression. MAML2 fluorescence in situ hybridization was positive in all cases, in both acinar and mucoepidermoid components. Two cases tested by next generation sequencing showed standard CRTC1-MAML2 fusions. MSANTD3 and NR4A3 fluorescence in situ hybridization on the other hand were negative. Evidence thus suggests that mucoacinar carcinoma represents an acinar variant morphology in MEC, rather than a true MEC-acinic cell carcinoma hybrid, or collision tumor. The acinar differentiation, SOX-10, DOG-1, and even focal NR4A3 reactivity may thus be diagnostic pitfalls.
Corded and Hyalinized and Spindled Endometrioid Endometrial Carcinoma: A Clinicopathologic and Molecular Analysis of 9 Tumors Based on the TCGA Classifier
Safdar, Nida S. MD*; Thompson, Emily F. MBChB†; Gilks, C. Blake MD†; Isacson, Christina MD‡; Bennett, Jennifer A. MD§; Clarke, Blaise MD?; Young, Robert H. MD*; Oliva, Esther MD*
doi : 10.1097/PAS.0000000000001737
August 2021 - Volume 45 - Issue 8 - p 1038-1046
Corded and hyalinized and spindled carcinomas are rare variants of endometrioid carcinoma (EC) characterized by cords of low-grade epithelial cells (±spindle cells) within a hyalinized stroma or spindled epithelial cells, respectively, that merge with conventional low-grade EC. Due to their “biphasic” morphology, these tumors are often misdiagnosed as carcinosarcoma. The clinicopathologic features including mismatch repair protein (PMS2 and MSH6) and p53 immunohistochemical expression and POLE mutational status of 9 corded and hyalinized and spindled endometrial ECs were evaluated and classified into The Cancer Genome Atlas (TCGA) based molecular subgroups. Beta-catenin immunohistochemistry was performed as a surrogate for CTNNB1 mutational status. The mean age at diagnosis was 49 years (range: 34 to 68?y) with staging information available for 6 patients: stage IA (n=1), stage IB (n=1), stage II (n=2), stage IIIA (n=1), stage IIIC1 (n=1). A prominent corded and hyalinized component was present in 7 ECs comprising 15% to 80% of the tumor with a minor (5% to 15%) spindled morphology in 5. Two additional tumors were composed of a low-grade spindled component comprising 25% to 30% of the neoplasm. Tumors were grade 1 (n=3), grade 2 (n=5), and grade 2 to 3 (n=1) and squamous differentiation was identified in 8/9. All tumors had preserved expression of mismatch repair proteins with 8 showing a p53 wild-type phenotype including the grade 2 to 3 EC; 1 grade 2, stage IB tumor exhibited a mutant pattern of expression. All (n=7) but 1 tumor demonstrated nuclear beta-catenin expression in the glandular, squamous, and corded or spindled components. POLE exonuclease domain mutations were absent in all tumors. Based on our findings, corded and hyalinized EC and EC with spindle cells are usually low grade, low stage, and present at a younger age and exhibit squamous differentiation at an increased frequency compared to typical EC. Unlike carcinosarcomas, which frequently harbor TP53 mutations, these tumors usually exhibit wild-type p53 and nuclear beta-catenin expression, indicative of underlying CTNNB1 mutations. According to the TCGA subgroups of endometrial carcinoma, the majority of corded and hyalinized and spindled EC appear to fall into the copy number low (“no specific molecular profile”) subgroup.
Congenital Myenteric Hypoganglionosis
Kapur, Raj P. MD, PhD*,†; Bellizzi, Andrew M. MD‡; Bond, Steffan MD§; Chen, Haiying MD?; Han, Jeong S. MD, PhD¶; LeGallo, Robin D. MD#; Midgen, Craig MD**; Poulin, Alysa A. MD, PhD††; Uddin, Naseem MD‡‡; Warren, Mikako MD§§; Velázquez Vega, José E. MD??; Zuppan, Craig W. MD¶¶
doi : 10.1097/PAS.0000000000001670
August 2021 - Volume 45 - Issue 8 - p 1047-1060
Congenital myenteric hypoganglionosis is a rare developmental disorder characterized clinically by severe and persistent neonatal intestinal pseudoobstruction. The diagnosis is established by the prevalence of small myenteric ganglia composed of closely spaced ganglion cells with sparse surrounding neuropil. In practice, the diagnosis entails familiarity with the normal appearance of myenteric ganglia in young infants and the ability to confidently recognize significant deviations in ganglion size and morphology. We review clinical, histologic, and immunohistochemical findings from 12 patients with congenital myenteric hypoganglionosis in comparison with similar data from age-matched controls and clearly delineate the diagnostic features of the condition. Practical guidelines are provided to assist surgical pathologists, who are likely to encounter this condition only infrequently. The diagnosis typically requires full-thickness intestinal biopsy as the abnormality is confined to the myenteric plexus in many patients. Immunohistochemistry for Hu C/D may be used to confirm hypoganglionosis. Reduced staining for calretinin and NeuN implicates a selective deficiency of intrinsic primary afferent neurons in this disease.
A Distinctive Adnexal (Usually Paratubal) Neoplasm Often Associated With Peutz-Jeghers Syndrome and Characterized by STK11 Alterations (STK11 Adnexal Tumor): A Report of 22 Cases
Bennett, Jennifer A. MD*; Young, Robert H. MD†; Howitt, Brooke E. MD‡; Croce, Sabrina MD§; Wanjari, Pankhuri MS*; Zhen, Chaojie BS*; Da Cruz Paula, Arnaud PhD?; Meserve, Emily MD¶; Schoolmeester, J. Kenneth MD#; Westbom-Fremer, Sofia MD**; Benzi, Eduardo MD††; Patil, Ninad M. MD††; Kooreman, Loes MD‡‡; El-Bahrawy, Mona MD§§; Zannoni, Gian Franco MD??; Krausz, Thomas MD*; McCluggage, W. Glenn FRCPath¶¶; Weigelt, Britta PhD?; Ritterhouse, Lauren L. MD, PhD†; Oliva, Esther MD†
doi : 10.1097/PAS.0000000000001677
August 2021 - Volume 45 - Issue 8 - p 1061-1074
We describe 22 examples of a novel, usually paratubal, adnexal tumor associated with Peutz-Jeghers syndrome in nearly 50% of cases that harbored STK11 alterations in all tested (n=21). The patients ranged from 17 to 66 years (median=39?y) and the tumors from 4.5 to 25.5?cm (median=11?cm). Most (n=18) were paratubal, with metastases noted in 11/22 (50%) and recurrences in 12/15 (80%). Morphologically, they were characterized by interanastomosing cords and trabeculae of predominantly epithelioid cells, set in a variably prominent myxoid to focally edematous stroma, that often merged to form tubular, cystic, cribriform, and microacinar formations, reminiscent of salivary gland-type tumors. The tumor cells were uniformly atypical, often with prominent nucleoli and a variable mitotic index (median=9/10?HPFs). The tumors were usually positive to a variable extent for epithelial (CAM5.2, AE1/AE3, cytokeratin 7), sex cord (calretinin, inhibin, WT1), and mesothelial (calretinin, D2-40) markers, as well as hormone receptors. PAX8, SF1, and GATA-3 were rarely positive, while claudin-4, FOXL2, and TTF-1 were consistently negative. All sequenced tumors (n=21) harbored alterations in STK11, often with a loss of heterozygosity event. There were no other recurrently mutated genes. Recurrent copy number alterations included loss of 1p and 11q, and gain of 1q, 15q, and 15p. Despite an extensive morphologic, immunohistochemical, and molecular evaluation, we are unable to determine with certainty the histogenesis of this unique tumor. Wolffian, sex cord stromal, epithelial, and mesothelial origins were considered. We propose the term STK11 adnexal tumor to describe this novel entity and emphasize the importance of genetic counseling in these patients as a significant number of neoplasms occur in association with Peutz-Jeghers syndrome.
Stage 4S Neuroblastoma: Molecular, Histologic, and Immunohistochemical Characteristics and Presence of 2 Distinct Patterns of MYCN Protein Overexpression—A Report From the Children’s Oncology Group
Kawano, Asuka MD*; Hazard, Florette K. MD†; Chiu, Bill MD‡; Naranjo, Arlene PhD§; LaBarre, Brian MS§; London, Wendy B. PhD?; Hogarty, Michael D. MD¶; Cohn, Susan L. MD#; Maris, John M. MD¶; Park, Julie R. MD**; Gastier-Foster, Julie M. PhD††; Ikegaki, Naohiko PhD‡‡; Shimada, Hiroyuki MD, PhD†
doi : 10.1097/PAS.0000000000001647
August 2021 - Volume 45 - Issue 8 - p 1075-1081
Stage 4S neuroblastoma (4SNB) is associated with spontaneous tumor regression and an excellent prognosis. However, a small group of the patients have a poor prognosis. One hundred eighty-five stage 4SNB cases filed at the Children’s Oncology Group Neuroblastoma Pathology Reference Laboratory were studied. MYCN oncogene status [non-amplified (NA) vs. Amplified (A)] determined by fluorescence in situ hybridization, MYC-family (MYCN/MYC) protein expression [no-overexpression(?)/(+/?) vs. overexpression(+)] by immunohistochemistry and histopathology by International Neuroblastoma Pathology Classification [Favorable Histology (FH) vs. Unfavorable Histology (UH)] with particular attention to nucleolar hypertrophy [NH(?) vs. (+)] were assessed with patient survival. One hundred forty-seven (79.5%) tumors were MYCN-NA, FH, MYC-family protein(?)/(+/?), and NH(?) with a good prognosis [88.5±3.1% 3-y event-free survival (EFS); 94.1±2.3% 3-y overall survival (OS)]. Among MYCN-NA tumors, 11 demonstrated MYCN protein(+) with a moderate and uniform (M/U) staining pattern: they were FH(10/11), NH(?), 1 showed MYC protein(+) simultaneously, and all patients are alive. Also found were 5 MYC protein(+) and MYCN(?)/(+/?) tumors; they were FH without NH (4/5), and all patients are alive. Among MYCN-A tumors, 18 had MYCN protein(+) with a strong and heterogeneous (S/H) staining pattern, 9 had UH (44.4±23.4% EFS/OS) and 9 had FH (68.6±19.2% EFS/OS), and 15 showed NH(+). Two tumors had MYCN protein(?)/(+/?) despite MYCN-A; both were FH and NH(?), and 1 patient died. S/H staining pattern of MYCN protein overexpression by immunohistochemistry was associated with MYCN amplification, NH(+) and a poor prognosis. In contrast, the M/U staining pattern was associated with MYCN nonamplification and NH(?), and had no adverse prognostic effects for the stage 4SNB patients.
Diffuse Gliomas of the Brainstem and Cerebellum in Adults Show Molecular Heterogeneity
Eschbacher, Kathryn L. MD*; Ida, Cristiane M. MD*; Johnson, Derek R. MD†,‡; Alvi, Mohammed A. MBBS§; Jenkins, Sarah M. MS?; Ruff, Michael W. MD‡; Kerezoudis, Panagiotis MD, MS§; Neth, Bryan J. MD, PhD‡; Pasion, Romela M. MS*; Daniels, David J. MD, PhD§; Kizilbash, Sani H. MD, MPH¶; Raghunathan, Aditya MD, MPH*
doi : 10.1097/PAS.0000000000001690
August 2021 - Volume 45 - Issue 8 - p 1082-1090
Posterior fossa (PF) diffuse gliomas in pediatric patients frequently harbor the H3 K27M mutation. Among adults, PF diffuse gliomas are rare, with limited data regarding molecular features and clinical outcomes. We identified 28 adult PF diffuse glioma patients (17 males; median: 50?y, range: 19 to 78?y), with surgery performed at our institution (13 brainstem; 15 cerebellum). Histologic subtypes included anaplastic astrocytoma (n=21), glioblastoma (n=6), and diffuse astrocytoma (n=1). Immunohistochemistry was performed for H3 K27M (n=26), IDH1-R132H (n=28), and ATRX (n=28). A 150-gene neuro-oncology-targeted next-generation sequencing panel was attempted in 24/28, with sufficient informative material in 15 (51.7%). Tumors comprised 4 distinct groups: driver mutations in H3F3A (brainstem=4; cerebellum=2), IDH1 (brainstem=4; cerebellum=4), TERT promotor mutation (brainstem=0; cerebellum=3), and none of these (n=5), with the latter harboring mutations of TP53, PDGFRA, ATRX, NF1, and RB1. All TERT promoter–mutant cases were IDH-wild-type and arose within the cerebellum. To date, 20 patients have died of disease, with a median survival of 16.3 months, 1-year survival of 67.5%. Median survival within the subgroups included: H3F3A=16.4 months, IDH mutant=113.4 months, and TERT promoter mutant=12.9 months. These findings suggest that PF diffuse gliomas affecting adults show molecular heterogeneity, which may be associated with patient outcomes and possible response to therapy, and supports the utility of molecular testing in these tumors.
Liver Pathology, Including MOC31 Immunohistochemistry, in Congenital Tufting Enteropathy
Chen, Sonja MBBS*; Goldsmith, Jeffrey D. MD*; Fawaz, Rima MD†; Al-Ibraheemi, Alyaa MD*; Perez-Atayde, Antonio R. MD, PhD*; Vargas, Sara O. MD*
doi : 10.1097/PAS.0000000000001710
August 2021 - Volume 45 - Issue 8 - p 1091-1097
Congenital tufting enteropathy (CTE) is a rare heritable cause of intractable diarrhea due to EPCAM mutation. Pathologic findings include intestinal villous atrophy, tufted discohesive tear-drop-shaped epithelium, and a normal brush border. In affected patients, absent intestinal epithelial cell adhesion molecule (EpCAM) expression results in loss of MOC31 immunostaining. CTE liver pathology has not yet been described. We identified CTE patients with liver biopsies and reviewed clinicopathologic material including MOC31 immunohistochemistry. Three CTE patients had 4 liver core biopsies (at ages 1, 5, 7, and 16?y), 2 for preintestinal transplant evaluation, and 2 (from a single patient) for pretreatment assessment of chronic hepatitis C; all had received parenteral nutrition (PN). All samples showed loss of biliary epithelial polarization and mild portal and lobular inflammation. Only the hepatitis C patient demonstrated fibrosis. One patient each had lobular neutrophilic microabscesses and macrovesicular steatosis. Proliferative ductular reactions were absent in CTE patients but present in all controls on PN for other reasons. MOC31 was absent in biliary epithelium and hepatocytes of all CTE patients; controls showed consistent strong membranous biliary epithelial and patchy membranous periportal hepatocyte staining. Our data show that, histologically, hepatopathy in CTE can be difficult to separate from comorbid disease including PN effect; however, the absent ductular reaction may be characteristic. MOC31 localization in the biliary epithelium and zone 1 hepatocytes of controls suggests these compartments of the liver might be most susceptible to effects of EpCAM deficiency. In addition, we validate the liver as suitable tissue for CTE diagnosis using MOC31 immunohistochemistry.
Morphologic and Molecular Findings in Myxoid Hepatic Adenomas
Rowan, Daniel J. MD*; Yasir, Saba MBBS*; Chen, Zongming E. PhD, MD*; Mounajjed, Taofic MD*; Erdogan Damgard, Sibel*; Cummins, Lisa*; Zhang, Lizhi MD*; Whitcomb, Emma MD†; Falck, Vince MBChB†; Simon, Sanford M. PhD‡; Singhi, Aatur D. MD§; Torbenson, Michael S. MD*
doi : 10.1097/PAS.0000000000001711
August 2021 - Volume 45 - Issue 8 - p 1098-1107
Myxoid hepatic adenomas are a rare subtype of hepatic adenomas with distinctive deposition of extracellular myxoid material between the hepatic plates. A total of 9 cases were identified in 6 women and 3 men with an average of 59±12 years. The myxoid adenomas were single tumors in 5 cases and multiple in 4 cases. In 1 case with multiple adenomas, the myxoid adenoma arose in the background of GNAS-mutated hepatic adenomatosis. Myxoid hepatic adenomas had a high frequency of malignant transformation (N=5 cases). They were characterized at the molecular level by HNF1A inactivating mutations, leading to loss of LFABP protein expression. In addition, myxoid adenomas had recurrent mutations in genes within the protein kinase A (PKA) pathway or in genes that regulate the PKA pathway: GNAS, CDKN1B (encodes p27), and RNF123. In sum, myxoid adenomas are rare, occur in older-aged persons, have a high risk of malignant transformation, and are characterized by the combined inactivation of HNF1A and additional mutations that appear to cluster in the PKA pathway.
SP142 PD-L1 Scoring Shows High Interobserver and Intraobserver Agreement in Triple-negative Breast Carcinoma But Overall Low Percentage Agreement With Other PD-L1 Clones SP263 and 22C3
Pang, Jia-Min B. PhD*; Castles, Belinda BPharm (Hons)†; Byrne, David J. BBiomedSc*; Button, Peter MSc‡; Hendry, Shona MBBS*; Lakhani, Sunil R. PhD§,?; Sivasubramaniam, Vanathi MBBS¶; Cooper, Wendy A. PhD#,**,††; Armes, Jane PhD‡‡; Millar, Ewan K.A. MD§§,??; Raymond, Wendy MD¶¶,##; Roberts-Thomson, Samuel MBBS***; Kumar, Beena MBBS†††; Burr, Marian PhD***,‡‡‡,§§§; Selinger, Christina PhD???; Harvey, Kate BBiotech (Hons)¶¶¶; Chan, Charles PhD###,****; Beith, Jane PhD**,††††; Clouston, David PhD‡‡‡‡; O’Toole, Sandra A. PhD#,**,††,¶¶¶; Fox, Stephen B. DPhil*,‡‡‡; kConFab
doi : 10.1097/PAS.0000000000001701
August 2021 - Volume 45 - Issue 8 - p 1108-1117
SP142 programmed cell death ligand 1 (PD-L1) status predicts response to atezolizumab in triple-negative breast carcinoma (TNBC). Prevalence of VENTANA PD-L1 (SP142) Assay positivity, concordance with the VENTANA PD-L1 (SP263) Assay and Dako PD-L1 IHC 22C3 pharmDx assay, and association with clinicopathologic features were assessed in 447 TNBCs. SP142 PD-L1 intraobserver and interobserver agreement was investigated in a subset of 60 TNBCs, with scores enriched around the 1% cutoff. The effect of a 1-hour training video on pretraining and posttraining scores was ascertained. At a 1% cutoff, 34.2% of tumors were SP142 PD-L1 positive. SP142 PD-L1 positivity was significantly associated with tumor-infiltrating lymphocytes (P <0.01), and node negativity (P=0.02), but not with tumor grade (P=0.35), tumor size (P=0.58), or BRCA mutation (P=0.53). Overall percentage agreement (OPA) for intraobserver and interobserver agreement was 95.0% and 93.7%, respectively, among 5 pathologists trained in TNBC SP142 PD-L1 scoring. In 5 TNBC SP142 PD-L1-naive pathologists, significantly higher OPA to the reference score was achieved after video training (posttraining OPA 85.7%, pretraining OPA 81.5%, P<0.05). PD-L1 status at a 1% cutoff was assessed by SP142 and SP263 in 420 cases, and by SP142 and 22C3 in 423 cases, with OPA of 88.1% and 85.8%, respectively. The VENTANA PD-L1 (SP142) Assay is reproducible for classifying TNBC PD-L1 status by trained observers; however, it is not analytically equivalent to the VENTANA PD-L1 (SP263) Assay and Dako PD-L1 IHC 22C3 pharmDx assay.
ISUP Consensus Definition of Cribriform Pattern Prostate Cancer
van der Kwast, Theodorus H. MD, PhD*; van Leenders, Geert J. MD, PhD†; Berney, Daniel M. MD‡; Delahunt, Brett MD§; Evans, Andrew J. MD, PhD*; Iczkowski, Kenneth A. MD?; McKenney, Jesse K. MD¶; Ro, Jae Y. MD?; Samaratunga, Hemamali FRCPA**; Srigley, John R. MD††; Tsuzuki, Toyo MD‡‡; Varma, Murali MD§§; Wheeler, Thomas M. MD??; Egevad, Lars MD, PhD¶¶
doi : 10.1097/PAS.0000000000001728
August 2021 - Volume 45 - Issue 8 - p 1118-1126
The presence of a cribriform pattern is now recognized as a clinically important, independent adverse prognostic indicator for prostate cancer. For this reason the International Society of Urological Pathology (ISUP) recently recommended its inclusion in standard reporting. In order to improve interobserver agreement as to the diagnosis of cribriform patterns, the ISUP assembled an international panel of 12 expert urogenital pathologists for the purpose of drafting a consensus definition of cribriform pattern in prostate cancer, and provide their opinions on a set of 32 images and on potential diagnostic criteria. These images were selected by the 2 nonvoting convenors of the study and included the main categories where disagreement was anticipated. The Delphi method was applied to promote consensus among the 12 panelists in their review of the images during 2 initial rounds of the study. Following a virtual meeting, convened to discuss selected images and diagnostic criteria, the following definition for cribriform pattern in prostate cancer was approved: “A confluent sheet of contiguous malignant epithelial cells with multiple glandular lumina that are easily visible at low power (objective magnification ×10). There should be no intervening stroma or mucin separating individual or fused glandular structures” together with a set of explanatory notes. We believe this consensus definition to be practical and that it will facilitate reproducible recognition and reporting of this clinically important pattern commonly seen in prostate cancer. The images and the results of the final Delphi round are available at the ISUP website as an educational slide set (https://isupweb.org/isup/blog/slideshow/cribriform-slide-deck/).
Clinical Utility of Anchored Multiplex Solid Fusion Assay for Diagnosis of Bone and Soft Tissue Tumors
Chebib, Ivan MD*; Taylor, Martin S. MD, PhD*; Nardi, Valentina MD*; Rivera, Miguel N. MD*; Lennerz, Jochen K. MD, PhD*; Cote, Gregory M. MD, PhD†; Choy, Edwin MD, PhD†; Lozano Calderón, Santiago A. MD, PhD‡; Raskin, Kevin A. MD‡; Schwab, Joseph H. MD‡; Mullen, John T. MD§; Chen, Yen-Lin E. MD?; Hung, Yin P. MD, PhD*; Nielsen, Gunnlaugur P. MD*; Deshpande, Vikram MBBS*
doi : 10.1097/PAS.0000000000001745
August 2021 - Volume 45 - Issue 8 - p 1127-1137
Sarcoma diagnosis has become increasingly complex, requiring a combination of morphology, immunohistochemistry, and molecular studies to derive specific diagnoses. We evaluated the role of anchored multiplex polymerase chain reaction–based gene fusion assay in sarcoma diagnostics. Between 2015 and 2018, bone and soft tissue sarcomas with fusion assay results were compared with the histologic diagnosis. Of 143 sarcomas tested for fusions, 43 (30%) had a detectable fusion. In review, they could be classified into 2 main categories: (1) 31 tumors with concordant morphologic and fusion data; and (2) 12 tumors where the fusion panel identified an unexpected rearrangement that played a significant role in classification. The overall concordance of the fusion assay results with morphology/immunohistochemistry or alternate confirmatory molecular studies was 83%. Collectively, anchored multiplex polymerase chain reaction–based solid fusion assay represents a robust means of detecting targeted fusions with known and novel partners. The predictive value of the panel is highest in tumors that show a monomorphic cell population, round cell tumors, as well as tumors rich in inflammatory cells. However, with an increased ability to discover fusions of uncertain significance, it remains essential to emphasize that the diagnosis of bone and soft tissue neoplasms requires the integration of morphology and immunohistochemical profile with these molecular methods, for accurate diagnosis and optimal clinical management of sarcomas.
Lymphadenopathy Associated With Neutralizing Anti-interferon-gamma Autoantibodies Could Have Monoclonal T-cell Proliferation Indistinguishable From Malignant Lymphoma and Treatable by Antibiotics: A Clinicopathologic Study
Yuan, Chang-Tsu MD*,†,‡; Wang, Jann-Tay MD, PhD§; Sheng, Wang-Huei MD, PhD§; Cheng, Pei-Yuan MS?; Kao, Chein-Jun MS¶; Wang, Jann-Yuan MD, PhD§; Chen, Chien-Yuan MD, PhD§; Liau, Jau-Yu MD†,?; Tsai, Jia-Huei MD†,?; Lin, Yi-Jyun MS†; Chen, Chung-Chung MS†; Chen, Yee-Chun MD, PhD§,#; Chang, Shan-Chwen MD, PhD§; Wu, Un-In MD§,**
doi : 10.1097/PAS.0000000000001731
August 2021 - Volume 45 - Issue 8 - p 1138-1150
Early recognition of adult-onset immunodeficiency associated with neutralizing anti-interferon gamma autoantibodies (anti-IFN? Abs) remains difficult, and misdiagnoses have been reported. Although febrile lymphadenopathy is among the most common initial manifestations of this disorder, no comprehensive clinicopathologic analysis of lymphadenopathy in patients with anti-IFN? Abs has been reported. Here, we describe 26 lymph node biopsy specimens from 16 patients. All patients exhibited concurrent disseminated nontuberculous mycobacterial infections, and 31% received a tentative diagnosis of lymphoma at initial presentation. We found 3 distinct histomorphologic patterns: well-formed granuloma (46%), suppurative inflammation or loose histiocytic aggregates (31%), and lymphoproliferative disorder (LPD, 23%). The latter shared some of the features of malignant T-cell lymphoma, IgG4-related disease, and multicentric Castleman disease. Half of the specimens with LPD had monoclonal T cells, and 33.3% were indistinguishable from angioimmunoblastic T-cell lymphoma as per current diagnostic criteria. All lymphadenopathy with LPD features regressed with antibiotics without administration of cytotoxic chemotherapy or immunotherapy. The median follow-up time was 4.3 years. Our study highlights the substantial challenge of distinguishing between lymphoma and other benign lymphadenopathy in the setting of neutralizing anti-IFN? Abs. Increased vigilance and multidisciplinary discussion among clinicians and pathologists are required to achieve the most appropriate diagnosis and management.
Primary Giant Cell Tumors of the Lung: A Clinicopathologic and Immunohistochemical Study of 3 Cases
Oramas, Diana M. MD; Moran, Cesar A. MD
doi : 10.1097/PAS.0000000000001686
August 2021 - Volume 45 - Issue 8 - p 1151-1154
Three cases of primary giant cell tumors of the lung akin to those described in the soft tissues are presented. The patients are 3 men between the ages of 43 and 54 years who presented with nonspecific symptoms of cough, chest pain, and shortness of breath. None of the patients had any prior history of malignancy anywhere else. Diagnostic imaging disclosed the presence of an intrapulmonary mass. All the patients underwent lobectomy. Grossly, the tumors were described as solid, slightly hemorrhagic, and measuring between 1.8 and 2.4?cm in greatest diameter. Histologically, the tumors were characterized by a dual population of multinucleated giant cells admixed with a mononuclear proliferation. Nuclear atypia was mild to moderate, and mitotic activity varied but was under 5 mitotic figures per 10 high power fields. Immunohistochemical stains showed positive staining for vimentin, CD68, and cathepsin K, whereas the tumors were negative for keratin, TTF-1, p40, S-100 protein, and SABT-2. Clinical follow-up was obtained in 2 patients who have remained alive and without evidence of recurrence or metastasis up to 12 months after surgery. One patient was lost to follow-up. The current neoplasms represent a tumor that to the best of our knowledge has not been reported as a primary neoplasm of the lung. The cases herein described represent an unusual occurrence and should be maintained in the differential diagnosis of primary pulmonary tumors rich in multinucleated giant cells.
