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Juan Rosai, MD (1940-2020)
Klimstra, David S. MD*,†; Young, Robert H. MD*,†
doi : 10.1097/PAS.0000000000001799
December 2021 - Volume 45 - Issue 12 - p e24-e34
Postdeployment Respiratory Syndrome in Soldiers With Chronic Exertional Dyspnea
Gutor, Sergey S. MD, PhD*; Richmond, Bradley W. MD, PhD*,†; Du, Rui-Hong MD*; Wu, Pingsheng PhD*,‡; Sandler, Kim L. MD§; MacKinnon, Grant MD?; Brittain, Evan L. MD?; Lee, Jae Woo MD¶; Ware, Lorraine B. MD*,#; Loyd, James E. MD*; Johnson, Joyce E. MD#; Miller, Robert F. MD*; Newman, John H. MD*; Rennard, Stephen I. MD**; Blackwell, Timothy S. MD*,†; Polosukhin, Vasiliy V. MD, PhD*
doi : 10.1097/PAS.0000000000001757
December 2021 - Volume 45 - Issue 12 - p 1587-1596
After deployment to Southwest Asia, some soldiers develop persistent respiratory symptoms, including exercise intolerance and exertional dyspnea. We identified 50 soldiers with a history of deployment to Southwest Asia who presented with unexplained dyspnea and underwent an unrevealing clinical evaluation followed by surgical lung biopsy. Lung tissue specimens from 17 age-matched, nonsmoking subjects were used as controls. Quantitative histomorphometry was performed for evaluation of inflammation and pathologic remodeling of small airways, pulmonary vasculature, alveolar tissue and visceral pleura. Compared with control subjects, lung biopsies from affected soldiers revealed a variety of pathologic changes involving their distal lungs, particularly related to bronchovascular bundles. Bronchioles from soldiers had increased thickness of the lamina propria, smooth muscle hypertrophy, and increased collagen content. In adjacent arteries, smooth muscle hypertrophy and adventitial thickening resulted in increased wall-to-lumen ratio in affected soldiers. Infiltration of CD4 and CD8 T lymphocytes was noted within airway walls, along with increased formation of lymphoid follicles. In alveolar parenchyma, collagen and elastin content were increased and capillary density was reduced in interalveolar septa from soldiers compared to control subjects. In addition, pleural involvement with inflammation and/or fibrosis was present in the majority (92%) of soldiers. Clinical follow-up of 29 soldiers (ranging from 1 to 15?y) showed persistence of exertional dyspnea in all individuals and a decline in total lung capacity. Susceptible soldiers develop a postdeployment respiratory syndrome that includes exertional dyspnea and complex pathologic changes affecting small airways, pulmonary vasculature, alveolar tissue, and visceral pleura.
Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms
Benton, Sarah BA*; Zhao, Jeffrey BA*; Zhang, Bin MS*; Bahrami, Armita MD†; Barnhill, Raymond L. MD‡; Busam, Klaus MD§; Cerroni, Lorenzo MD?; Cook, Martin G. MD, FRCPath¶; de la Fouchardière, Arnaud MD, PhD#; Elder, David E. MBChB, FRCPA**; Johansson, Iva MD††; Landman, Gilles MD, PhD‡‡; Lazar, Alexander MD, PhD§§; LeBoit, Philip MD??; Lowe, Lori MD¶¶; Massi, Daniela MD, PhD##; Duncan, Lyn M. MD***; Messina, Jane MD†††; Mihic-Probst, Daniela MD‡‡‡; Mihm, Martin C. Jr MD§§§; Piepkorn, Michael W. MD, PhD???,¶¶¶; Schmidt, Birgitta MD###; Scolyer, Richard A. MD****,††††,‡‡‡‡; Shea, Christopher R. MD§§§§; Tetzlaff, Michael T. MD, PhD??; Tron, Victor A. MD, FRCPC????,¶¶¶¶; Xu, Xiaowei MD, PhD**; Yeh, Iwei MD, PhD??; Yun, Sook Jung MD, PhD####; Zembowicz, Artur MD, PhD*****; Gerami, Pedram MD*
doi : 10.1097/PAS.0000000000001753
December 2021 - Volume 45 - Issue 12 - p 1597-1605
Atypical Spitzoid melanocytic tumors are diagnostically challenging. Many studies have suggested various genomic markers to improve classification and prognostication. We aimed to assess whether next-generation sequencing studies using the Tempus xO assay assessing mutations in 1711 cancer-related genes and performing whole transcriptome mRNA sequencing for structural alterations could improve diagnostic agreement and accuracy in assessing neoplasms with Spitzoid histologic features. Twenty expert pathologists were asked to review 70 consultation level cases with Spitzoid features, once with limited clinical information and again with additional genomic information. There was an improvement in overall agreement with additional genomic information. Most significantly, there was increase in agreement of the diagnosis of conventional melanoma from moderate (?=0.470, SE=0.0105) to substantial (?=0.645, SE=0.0143) as measured by an average Cohen ?. Clinical follow-up was available in all 70 cases which substantiated that the improved agreement was clinically significant. Among 3 patients with distant metastatic disease, there was a highly significant increase in diagnostic recognition of the cases as conventional melanoma with genomics (P<0.005). In one case, none of 20 pathologists recognized a tumor with BRAF and TERT promoter mutations associated with fatal outcome as a conventional melanoma when only limited clinical information was provided, whereas 60% of pathologists correctly diagnosed this case when genomic information was also available. There was also a significant improvement in agreement of which lesions should be classified in the Spitz category/WHO Pathway from an average Cohen ? of 0.360 (SE=0.00921) to 0.607 (SE=0.0232) with genomics.
Clinicopathologic Analysis of Primary Adrenal Diffuse Large B-Cell Lymphoma
Kawano, Tasuku MD*,†; Tsuyuki, Yuta MD, PhD*; Suzuki, Yuka MD, PhD*; Shimada, Kazuyuki MD, PhD‡; Kato, Seiichi MD, PhD§; Takahara, Taishi MD, PhD?; Mori, Mayuko MD*; Nakaguro, Masato MD, PhD*; Sakakibara, Ayako MD, PhD*; Nakamura, Shigeo MD, PhD*; Satou, Akira MD, PhD?
doi : 10.1097/PAS.0000000000001809
December 2021 - Volume 45 - Issue 12 - p 1606-1615
Primary adrenal diffuse large B-cell lymphoma (PA-DLBCL) is rare. We investigate 23 Japanese patients with PA-DLBCL to understand the clinicopathologic features and biological behavior of this disease. The 17 males and 6 females had a median age of 74 years (range: 40 to 86?y). Tumor cells harbored Epstein-Barr virus–encoded small RNA (EBER) in 9 (39%) samples, including samples from the 2 patients with methotrexate-associated B-cell lymphoproliferative disorder. Programmed cell death ligand 1 (PD-L1) expression was detected in tumor cells of 6 (26%) samples, including 1 EBER+ and 5 EBER? samples. Four (17%) patients exhibited an intravascular proliferating pattern, and all 4 patient samples showed positive staining for PD-L1 in tumor cells. Among those patients, 3 showed intravascular proliferating pattern accompanied by a diffuse extravascular proliferation of tumor cells, and 1 patient was diagnosed with intravascular large B-cell lymphoma. We divided the 23 patients into 3 groups: EBER+ (n=9, 39%), EBER?PD-L1+ (n=5, 22%), and EBER?PD-L1? (n=9, 39%). A comparison of the outcomes among the 3 groups showed significant differences in overall survival (P=0.034). The EBER+ group had the worst prognosis, and the EBER?PD-L1? group had the best prognosis. We also compared the outcomes among the 3 groups that received rituximab-containing chemotherapies. Both the overall survival and progression-free survival were significantly different among these groups (P<0.001 and P=0.002, respectively). In conclusion, we evaluated 3 types of PA-DLBCL and found that each had unique clinical, pathologic, and prognostic features. Our results suggested that immune senescence, iatrogenic immunodeficiency, and immune evasion contribute to the development of PA-DLBCL.
CD34-negative Solitary Fibrous Tumor
Dermawan, Josephine K. MD, PhD; Rubin, Brian P. MD, PhD; Kilpatrick, Scott E. MD; Gjorgova Gjeorgjievski, Sandra MD; Fritchie, Karen J. MD; Goldblum, John R. MD; McKenney, Jesse K. MD; Billings, Steven D. MD
doi : 10.1097/PAS.0000000000001717
December 2021 - Volume 45 - Issue 12 - p 1616-1625
CD34-negative solitary fibrous tumors (SFTs) are rare and have not been comprehensively studied. We retrospectively reviewed all cases of SFT confirmed with STAT6 immunohistochemistry and/or STAT6 gene fusion between 2013 and 2020 and collected pertinent clinicopathologic parameters. Of a total of 244 cases, 25 (10%) lacked CD34 expression by immunohistochemistry. Compared with CD34-positive SFT, CD34-negative SFT are more likely to arise in the head and neck area (32% vs. 24%, P=0.02) and present as metastatic disease (28% vs. 1%, P<0.0001). A significantly higher percentage of CD34-negative SFT exhibit high-grade cytologic atypia (hypercellularity, round cell or anaplastic morphology, nuclear pleomorphism, etc.) (48% vs. 22%, P=0.0073). There are no significant differences in the distributions of age, sex, tumor size, mitotic count, tumor necrosis, or risk stratification between CD34-negative and CD34-positive SFT. In addition, only 56% of CD34-negative SFT display a typical hemangiopericytoma-like vascular pattern. Special histologic features among CD34-negative SFT include prominent alternating hypercellular or fibrous and hypocellular myxoid areas with curvilinear vessels mimicking low-grade fibromyxoid sarcoma, pulmonary edema-like microcystic changes, and prominent amianthoid collagen fibers. In conclusion, compared with their CD34-positive counterparts, CD34-negative SFT is more likely to present as metastatic disease, show high-grade nuclear atypia, and lack the characteristic hemangiopericytoma-like vasculature, posing a unique diagnostic challenge. The use of STAT6 immunohistochemistry and/or molecular studies may be prudent in soft tissue tumors that appear CD34 negative and lack conventional SFT histopathologic characteristics.
Familial Adenomatous Polyposis–associated Traditional Serrated Adenoma of the Small Intestine
Alruwaii, Zainab I. MD*; Chianchiano, Peter MS*; Larman, Tatianna MD*; Wilentz, Alexander*; Wood, Laura D. MD, PhD*,†,‡; Montgomery, Elizabeth A. MD*
doi : 10.1097/PAS.0000000000001770
December 2021 - Volume 45 - Issue 12 - p 1626-1632
Familial adenomatous polyposis (FAP) is an inherited cancer predisposition syndrome associated with numerous gastrointestinal tract adenomatous polyps, as well as gastric fundic gland polyps and pyloric gland adenomas in the upper gastrointestinal tract. While colonic FAP-associated traditional serrated adenomas (TSAs) have been reported in a few studies, small bowel FAP-associated adenomas with TSA morphology have not been characterized. This study describes the clinicopathologic and molecular findings of this type of adenoma in the small bowel of patients with FAP. We reviewed small bowel adenomas in 45 consecutive FAP patients to identify adenomas with zones showing slit-like serrations, cells with eosinophilic cytoplasm, ectopic crypt formation, and vesicular nuclei. Sporadic small bowel adenomas from 51 consecutive patients were also reviewed for adenomas with the same features. Of the 177 polyps from 45 FAP patients and 60 polyps from 51 nonsyndromic patients, 18 TSAs from 9 FAP patients (20%) and 10 TSAs from the sporadic group (19.6%) were identified. FAP patients presented at a younger age than nonsyndromic patients (median: 43 vs. 66; P=0.0048). FAP-associated TSAs were asymptomatic and smaller than sporadic TSAs (median size: 0.6 vs. 2.5?cm; P=0.00006). Immunostaining for ?-catenin and testing for BRAF and KRAS mutations were performed in a subset of the cohort. Nuclear ?-catenin was seen in 1 FAP-associated TSA and 3 nonsyndromic TSAs. All TSAs (FAP-associated and nonsyndromic) showed wild-type BRAF, while KRAS mutations were identified only in the nonsyndromic setting. In summary, small bowel FAP-associated and sporadic TSAs share a similar morphology, and the BRAF-serrated pathway does not contribute to their pathogenesis.
Wnt Family Member 9b (Wnt9b) Is a New Sensitive and Specific Marker for Breast Cancer
Lu, Shaolei MD, PhD; Yakirevich, Evgeny MD, DSc; Yang, Dongfang MSc; Xiao, Ying BSc; Wang, Li Juan MD, PhD; Wang, Yihong MD, PhD
doi : 10.1097/PAS.0000000000001784
December 2021 - Volume 45 - Issue 12 - p 1633-1640
Confirming the tumor origin is often a diagnostic challenge in pathology and carries significant therapeutic impacts. Cytokeratin 7, estrogen receptor, and GATA binding protein 3 (GATA3) are well-established diagnostic markers frequently used to support a tumor’s breast origin. However, their specificities still have room to improve. Many nonbreast tumors express cytokeratin 7 and estrogen receptor, and urothelial tumors frequently express GATA3. There is a practical need for a new breast lineage marker that is sensitive and specific. Wnt family member proteins play critical roles in embryo development, tissue homeostasis and tumor development through ?-catenin dependent and independent pathways. The current study evaluated Wnt9b and GATA3 expression in 163 primary breast cancers, 63 metastatic breast cancers, and 525 nonbreast epithelial tumors. The positive rates of Wnt9b and GATA3 in primary breast cancer were both 98.7%. The positive rates in metastatic breast cancer were 87.3% for Wnt9b and 96.8% for GATA3. For nonbreast tumors, including 64 cases of urothelial carcinoma, Wnt9b was negative in all except salivary gland carcinomas. The study demonstrated that Wnt9b is a breast cancer marker with similar sensitivity as GATA3 but with greater specificity than GATA3 and may ultimately become a useful diagnostic tool in routine surgical pathology practice.
Pediatric Hepatocellular Adenomas
Pacheco, Maria Cristina MD*,†; Torbenson, Michael S. MD‡; Wu, Tsung-Teh MD, PhD‡; Kakar, Sanjay MD§; Jain, Dhanpat MD?; Yeh, Matthew M. MD, PhD†,¶
doi : 10.1097/PAS.0000000000001763
December 2021 - Volume 45 - Issue 12 - p 1641-1647
Hepatocellular adenomas are rare in children. A large study focused on pediatric patients has not been undertaken. A natural language search was performed at 5 institutions for hepatocellular adenomas in patients younger than 21 years old. Clinical characteristics as well as immunohistochemical staining profile was reviewed and adenomas subtyped per standard classification. Patients were divided into prepubescent and postpubescent age group. Thirty-one patients were included. Eleven (35%) were male and 10 (32%) were prepubescent. Fifteen (54%) of 28 patients with known clinical histories had adenomas associated with a syndrome. The percentage of the different adenoma subtypes was: 16% ?-catenin activated, 10% combined inflammatory and ?-catenin activated, 29% HFN1?-inactivated, 35% inflammatory, and 10% unclassified subtype by immunohistochemical staining. Interestingly 53% of patients with syndromes were male, while 85% of patients in the nonsyndromic group were female. The total number of ?-catenin activated tumors was greater in the syndromic group (5/15, 33%) and prepubescent group (5/10, 50%) than in the nonsyndromic group (2/13, 16%) and postpubescent group (3/21, 14%), P=0.4 and 0.07, respectively. Inflammatory type adenoma was more frequent in the postpubescent (10/21, 48%) than in the prepubescent group (1/10, 10%), P=0.06, trending toward significance. Pediatric patients with hepatocellular adenomas frequently have syndromes, especially in the prepubescent group. In patients with syndromes a greater percentage of adenomas were ?-catenin activated. In patients without a known syndrome the distribution of hepatocellular adenoma subtypes appears similar to adults.
Florid Foreign Body-type Giant Cell Response to Keratin Is Associated With Improved Overall Survival in Patients Receiving Preoperative Therapy for Esophageal Squamous Cell Carcinoma
Chen, Wei MD*; Zhao, Lei MD, PhD*; Agoston, Agoston MD, PhD*; White, Abby DO†; Mazzola, Emanuele PhD‡; Boyle, Patrick J. BA§; Deshpande, Vikram MBBS, MD?; Hornick, Jason L. MD, PhD*; Bueno, Raphael MD†; Bass, Adam J. MD¶; Enzinger, Peter MD¶; Mamon, Harvey MD, PhD§; Redston, Mark MD*; Patil, Deepa T. MD*
doi : 10.1097/PAS.0000000000001797
December 2021 - Volume 45 - Issue 12 - p 1648-1660
While most resection specimens from patients with neoadjuvantly treated esophageal squamous cell carcinoma show therapy-related changes in the form of inflammation and fibrosis, others harbor a florid foreign body-type giant cell response to keratin debris. The purpose of our study was to perform a detailed clinicopathologic analysis of these histologic types of treatment responses and correlate these findings with patient outcome. Clinical and pathologic parameters from 110 esophagogastrectomies were recorded and analyzed. Two main types of histologic responses were observed: inflammatory-predominant response (59%) and florid foreign body-type giant cell response to keratin (41%). Irrespective of cG, cTNM, and amount of residual cancer, florid foreign body-type giant cell reaction was predominantly noted deep within the esophageal wall, while the inflammatory response was restricted to the mucosa, submucosa, and inner half of muscularis propria. Patients with foreign body-type giant cell response showed significantly better overall survival compared with the inflammatory response group (log-rank test P=0.015). Florid foreign body-type giant cell response was the only factor associated with improved survival in a multivariable analysis for overall survival (hazard ratio=0.5; 95% confidence interval=0.3-1.0; P=0.038), but not in the model for disease-specific survival, whereas ypTNM stage II was the only significant risk factor for disease-specific survival in multivariable analysis (hazard ratio=3.4; 95% confidence interval=1.0-11.2; P=0.047). Our results suggest that in addition to the College of American Pathologists Tumor Regression Score and ypTNM stage, subtype of histologic response to therapy may represent another prognostic marker for neoadjuvantly treated esophageal squamous cell carcinoma.
High-grade Papillary Early Gastric Carcinoma With High Risk for Lymph Node Metastasis and Poor Prognosis
Cheng, Yuqing MD, MS*; Du, Mingzhan MD, PhD†; Zhou, Xiaoli MD, PhD*; Guo, Lingchuan MD, PhD†; Xu, Kequn MD, PhD‡; Huang, Jin MD, PhD§; Huang, Qin MD, PhD*,?
doi : 10.1097/PAS.0000000000001759
December 2021 - Volume 45 - Issue 12 - p 1661-1668
Papillary early gastric carcinoma (EGC) is believed to have a low risk of lymph node metastasis (LNM) and thus can be resected endoscopically. We observed anecdotally that some papillary EGC tumors showed conspicuous high-grade dysplastic features, but the significance of these observations is unknown. In this bicenter study we investigated papillary EGCs that were divided into high-grade (n=96) and low-grade (n=118) groups among 1136 consecutive EGC radical resection cases. Concurrent 464 well-moderately differentiated tubular EGCs were served as the control group. Compared with low-grade papillary and well-moderately differentiated tubular EGCs, high-grade papillary EGC displayed significantly larger sizes (mean 2.51?cm), higher frequencies of the elevated macroscopic type (51%), lymphovascular invasion (LVI) (38.5%), and LNM (31.2%). Low-grade papillary EGCs exhibited a higher prevalence of the elevated macroscopic type, but not LVI nor LNM, compared with tubular EGC. Independent risk factors for LNM included high-grade histology, female sex, distal location, submucosal invasion, and LVI. The 5-year overall survival rate was significantly lower in high-grade (79.6%) papillary than in low-grade (88.9%) papillary or tubular (92.8%) EGCs, while no significant difference in prognosis was observed in the latter 2 groups. Age of 66 years or older and LNM were independent risk factors for overall survival. In conclusions, high-grade papillary EGC was associated with high frequencies of LVI, LNM, and poor prognosis, and thus unsuitable for endoscopic therapy, while low-grade papillary EGC showed clinicopathologic features and prognosis similar to well-moderately differentiated tubular EGC and may be treated endoscopically in appropriate clinical settings.
Expanding the Spectrum of EWSR1-NFATC2-rearranged Benign Tumors
Ong, Sheena L.M. BSc*; Lam, Suk Wai MD*; van den Akker, Brendy E.W.M. BSc*; Kroon, Herman M. MD, PhD†; Briaire-de Bruijn, Inge H. BSc*; Cleven, Arjen H.G. MD, PhD*; Savci-Heijink, Dilara C. MD, PhD‡; Cleton-Jansen, Anne-Marie PhD*; Baumhoer, Daniel MD, PhD§; Szuhai, Karoly MD, PhD?; Bovée, Judith V.M.G. MD, PhD*
doi : 10.1097/PAS.0000000000001748
December 2021 - Volume 45 - Issue 12 - p 1669-1681
A simple bone cyst (SBC) is a cystic bone lesion predominantly affecting young males. The cyst is lined by a fibrous membrane and filled with serosanguinous fluid. EWSR1/FUS-NFATC2 rearrangements were recently identified in SBC. We here report exactly the same rearrangement in 3 lesions diagnosed as vascular malformations of 2 elderly patients. In total, through Archer FusionPlex, fluorescence in situ hybridization and/or reverse transcriptase-polymerase chain reaction the EWSR1-NFATC2 rearrangement was identified in 6 of 9 SBC, 3 of 12 benign vascular tumors, and none of 5 aneurysmal bone cyst lacking USP6 fusion. Using fluorescence in situ hybridization, it was apparent that amplification of the fusion, as seen in EWSR1-NFATC2 round cell sarcomas, was absent, and that in the vascular tumors the fusion was present both in the lining cells as well as in the surrounding spindle cells. Of note, not all of the spaces in the vascular malformations were lined by endothelial cells. Aggrecan was positive in all cases but was not specific. NKX2-2 and NKX3-1 staining were negative in all cases. Thus, even though the overlap between the 2 entities is limited to the presence of few thick-walled cysts lacking endothelial lining in the benign vascular malformations, the spectrum of benign tumors containing NFATC2 fusions should be expanded and contains not only SBC in the young, but also vascular malformation/hemangioma in elderly patients.
DEK-AFF2 Carcinoma of the Sinonasal Region and Skull Base
Rooper, Lisa M. MD*,†; Agaimy, Abbas MD‡; Dickson, Brendan C. MD, MSc§,?; Dueber, Julie C. MD¶; Eberhart, Charles G. MD, PhD*,†,#; Gagan, Jeffrey MD, PhD**; Hartmann, Arndt MD‡; Khararjian, Armen MD, MBA††; London, Nyall R. MD, PhD‡‡; MacMillan, Christina M. MD§,?; Palsgrove, Doreen N. MD**; Nix, J. Stephen MD*; Sandison, Ann MBChB§§; Stoehr, Robert PhD‡; Truong, Tra MD§,??; Weinreb, Ilan MD§,¶¶; Bishop, Justin A. MD**
doi : 10.1097/PAS.0000000000001741
December 2021 - Volume 45 - Issue 12 - p 1682-1693
A novel DEK-AFF2 fusion was recently reported in 4 nonkeratinizing squamous cell carcinomas of the sinonasal region and skull base, including 1 with exceptional response to immunotherapy, but it is not yet clear if this rearrangement defines a unique clinicopathologic category or represents a rare event. This study aims to characterize a larger cohort of carcinomas with DEK-AFF2 fusions to assess whether they truly constitute a distinctive entity. Among 27 sinonasal and skull base nonkeratinizing squamous cell carcinoma that were negative for human papillomavirus and Epstein-Barr virus, RNA sequencing identified DEK-AFF2 fusions in 13 cases (48%). Nine were centered in the nasal cavity, 2 in the middle ear/temporal bone, 1 in the nasopharynx, and 1 in the orbit. These tumors displayed recurrent histologic features including (1) complex endophytic and exophytic, frequently papilloma-like growth, (2) transitional epithelium with eosinophilic to amphophilic cytoplasm, (3) absent or minimal keratinization with occasional compact keratin pearls, (4) monotonous nuclei, and (5) prominent tumor-infiltrating neutrophils or stromal lymphocytes. This appearance not only overlaps with high-grade basaloid sinonasal carcinomas but also with benign papillomas and tumors reported as low-grade papillary Schneiderian carcinoma. However, DEK-AFF2 carcinomas showed frequent local recurrence, cervical lymph node metastases, and distant metastasis with 2 deaths from disease, confirming they are aggressive malignancies despite relatively bland histology. Overall, the distinctive molecular, histologic, and clinical features of DEK-AFF2 carcinomas suggest they represent a unique entity in the sinonasal region. This tumor merits increased pathologic recognition to better understand its prognostic and therapeutic implications.
Nonampullary Duodenal Adenomas in Familial Adenomatous Polyposis and Sporadic Patients Lack the DNA Content Abnormality That Is Characteristic of the Adenoma-Carcinoma Sequence Involved in the Development of Other Gastrointestinal Malignancies
Mohammed, Nebil MD*; Rabinovitch, Peter S. MD, PhD†; Wang, Dongliang PhD‡; K?vári, Bence P. MD, PhD§; Mattis, Aras N. MD, PhD*; Lauwers, Gregory Y. MD§; Choi, Won-Tak MD, PhD*
doi : 10.1097/PAS.0000000000001754
December 2021 - Volume 45 - Issue 12 - p 1694-1702
Nonampullary duodenal adenomas (NADAs) develop sporadically or in the setting of a hereditary syndrome such as familial adenomatous polyposis (FAP). Although they are thought to progress into duodenal adenocarcinomas via an adenoma to carcinoma sequence similar to colorectal cancer, limited data suggested that they may be biologically dissimilar to colorectal adenomas. The clinicopathologic features of 71 patients diagnosed with NADAs (37 FAP and 34 sporadic) were analyzed. From the 71 patients, 89 NADA biopsies (42 FAP and 47 sporadic) were evaluated by DNA flow cytometry. Eighty-two samples showed low-grade dysplasia, and 7 demonstrated high-grade dysplasia (HGD). Twenty-one low-grade adenomas of the ileal pouch (n=19) and jejunum (n=2) from 15 FAP patients who underwent total proctocolectomy were also analyzed by DNA flow cytometry. The FAP patients were more likely to be younger (mean: 28?y) and have multifocal disease (92%) than the sporadic patients (66?y and 24%, respectively) (P<0.001). Most NADAs presented as polypoid lesions (87%) in the duodenal bulb and/or second portion of the duodenum (94%). Sporadic NADAs (mean: 2.4 cm) were significantly larger than FAP-related NADAs (1.3?cm) (P=0.005). Three (4%) patients (2 sporadic and 1 FAP) had high-grade NADAs at the first endoscopy, while the remaining 68 (96%) patients had low-grade dysplasia. Two additional sporadic and 1 FAP patients developed HGD on follow-up. Although the overall detection rate of advanced neoplasia (either HGD or adenocarcinoma) was similar between the FAP (n=5; 14%) and sporadic groups (n=4; 12%) (P=1.000), 3 FAP patients (all with Spigelman stage III to IV) developed adenocarcinoma in the duodenum (n=2) or in the ileal pouch (n=1) within a mean follow-up time of 76 months, while no adenocarcinoma was found in the sporadic group. Of the 37 FAP patients, 29 (78%) had a history of total proctocolectomy, and 15 (52%) developed low-grade adenomas in the ileal pouch with (n=2) or without (n=13) jejunal involvement (vs. 0% in the sporadic patients, P<0.001). All 15 patients had ?Spigelman stage II. Aneuploidy was detected in only 1 (1%) sporadic NADA with HGD, whereas the remaining 109 duodenal, ileal pouch, and jejunal adenomas showed normal DNA content. The overall 3-, 9-, and 15-year detection rates of adenocarcinoma (in the duodenum and ileal pouch) in all NADA patients were 1.4%, 7.2%, and 18.8%, respectively. Three-, 9-, and 15-year detection rates of adenocarcinoma in the FAP patients were 2.7%, 9.7%, and 22.6%, respectively, while these rates remained at 0% in the sporadic patients. In conclusion, FAP-related NADAs have distinct clinicopathologic features compared with their sporadic counterpart. However, the vast majority of both FAP-related and sporadic NADAs (99%) lack the DNA content abnormality that is characteristic of the typical adenoma-carcinoma sequence involved in other gastrointestinal carcinogenesis. Although adenocarcinoma is more likely to develop in FAP patients with a high adenoma burden, probably due to the higher likelihood that some advanced lesions are missed endoscopically, FAP-related and sporadic NADAs may have a comparable risk of developing advanced neoplasia on a per-adenoma basis.
Crohn Disease Infrequently Affects the Appendix and Rarely Causes Granulomatous Appendicitis
Mostyka, Maria DO*; Fulmer, Clifton G. MD, PhD†; Hissong, Erika M. MD‡; Yantiss, Rhonda K. MD*
doi : 10.1097/PAS.0000000000001734
December 2021 - Volume 45 - Issue 12 - p 1703-1706
Data from previous studies suggest Crohn disease of the appendix accounts for ?25% of granulomatous appendicitis cases. However, we have found that granulomatous inflammation in appendectomy specimens rarely heralds Crohn disease. We suspect that appendiceal involvement by Crohn disease is uncommon, even when patients have severe ileocolonic inflammation. We performed this study to determine the prevalence and nature of appendiceal inflammation among patients with Crohn disease. We reviewed 100 ileocolic specimens with strictures and fistulizing Crohn disease for the nature and distribution of inflammatory changes in the appendix and compared them with 100 appendices on colectomy specimens from age-matched and sex-matched patients with ulcerative colitis. We also evaluated 27 additional cases of granulomatous appendicitis in appendectomy specimens to determine the frequency with which this finding represented Crohn disease. The appendix was usually normal (26%) or showed fibrous obliteration (50%) in ileocolic resection specimens from patients with Crohn disease. Mucosal inflammation was much less common in appendices from patients with Crohn disease than ulcerative colitis (6% vs. 28%, P<0.0001); only 4 cases contained epithelioid granulomata, 3 showed mural fibrosis and lymphoid aggregates, and 10 displayed only periappendiceal inflammation. None of the patients with granulomatous appendicitis in appendectomy specimens had, or developed, evidence of Crohn disease. We conclude that Crohn disease infrequently affects the appendix. Interval appendectomy and infection are more important considerations when appendectomy specimens feature granulomatous inflammation and/or mural lymphoid aggregates, especially if there is no history of idiopathic inflammatory bowel disease.
Clinicopathologic and Genomic Characterization of Inflammatory Myofibroblastic Tumors of the Head and Neck
Kerr, Darcy A. MD*,†; Thompson, Lester D.R. MD‡; Tafe, Laura J. MD*,†; Jo, Vickie Y. MD§; Neyaz, Azfar MD?; Divakar, Prashanthi MD¶; Paydarfar, Joseph A. MD†,¶; Pastel, David A. MD†,#; Shirai, Keisuke MD, MSc†,**; John, Ivy MD††; Seethala, Raja R. MD††; Salgado, Claudia M. MD, PhD‡‡; Deshpande, Vikram MD?; Bridge, Julia A. MD§§,??; Kashofer, Karl PhD¶¶; Br?i?, Iva MD¶¶; Linos, Konstantinos MD*,†
doi : 10.1097/PAS.0000000000001735
December 2021 - Volume 45 - Issue 12 - p 1707-1719
Inflammatory myofibroblastic tumor (IMT) is a distinctive fibroblastic and myofibroblastic spindle cell neoplasm with an accompanying inflammatory cell infiltrate and frequent receptor tyrosine kinase activation at the molecular level. The tumor may recur and rarely metastasizes. IMT is rare in the head and neck region, and limited information is available about its clinicopathologic and molecular characteristics in these subsites. Therefore, we analyzed a cohort of head and neck IMTs through a multi-institutional approach. Fourteen cases were included in the provisional cohort, but 1 was excluded after molecular analysis prompted reclassification. Patients in the final cohort included 7 males and 6 females, with a mean age of 26.5 years. Tumors were located in the larynx (n=7), oral cavity (n=3), pharynx (n=2), and mastoid (n=1). Histologically, all tumors showed neoplastic spindle cells in storiform to fascicular patterns with associated chronic inflammation, but the morphologic spectrum was wide, as is characteristic of IMT in other sites. An underlying fusion gene event was identified in 92% (n=11/12) of cases and an additional case was ALK-positive by IHC but could not be evaluated molecularly. ALK represented the driver in all but 1 case. Rearrangement of ALK, fused with the TIMP3 gene (n=6) was most commonly detected, followed by 1 case each of the following fusion gene partnerships: TPM3-ALK, KIF5B-ALK, CARS-ALK, THBS1-ALK, and a novel alteration, SLC12A2-ROS1. The excluded case was reclassified as spindle cell rhabdomyosarcoma after detection of a FUS-TFCP2 rearrangement and retrospective immunohistochemical confirmation of rhabdomyoblastic differentiation, illustrating an important diagnostic pitfall. Two IMT patients received targeted therapy with crizotinib, with a demonstrated radiographic response. One tumor recurred but none metastasized. These results add to the growing body of evidence that kinase fusions can be identified in the majority of IMTs and that molecular analysis can lead to increased diagnostic accuracy and broadened therapeutic options for patients.
Adenocarcinoma of the Rete Testis
Al-Obaidy, Khaleel I. MD; Collins, Katrina MD; Idrees, Muhammad T. MD; Ulbright, Thomas M. MD
doi : 10.1097/PAS.0000000000001771
December 2021 - Volume 45 - Issue 12 - p 1720-1724
GTF2A1-NCOA2-Associated Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT) Shows Focal Rhabdoid Morphology and Aggressive Behavior
Devereaux, Kelly A. MD, PhD*; Kertowidjojo, Elizabeth MD, PhD*; Natale, Kristen DO†; Ewalt, Mark D. MD*; Soslow, Robert A. MD*; Hodgson, Anjelica MD*
doi : 10.1097/PAS.0000000000001786
December 2021 - Volume 45 - Issue 12 - p 1725-1728
Congenital Myenteric Hypoganglionosis: Erratum
doi : 10.1097/PAS.0000000000001842
December 2021 - Volume 45 - Issue 12 - p 1728
Juan Rosai, MD (1940-2020)
Klimstra, David S. MD*,†; Young, Robert H. MD*,†
doi : 10.1097/PAS.0000000000001782
December 2021 - Volume 45 - Issue 12 - p 1729-1731
Samuel Alan Yousem, MD (October 17, 1956 to August 17, 2021)
Colby, Thomas V. MD*; Myers, Jeffrey L. MD†
doi : 10.1097/PAS.0000000000001823
December 2021 - Volume 45 - Issue 12 - p 1732-1733
