Annals of Diagnostic Pathology

Large language models in pathology: A comparative study of ChatGPT and Bard with pathology trainees on multiple-choice questions
Du W, Jin X, Harris JC, Brunetti A, Johnson E, Leung O, Li X, Walle S, Yu Q, Zhou X, Bian F, McKenzie K, Kanathanavanich M, Ozcelik Y, El-Sharkawy F and Koga S
Large language models (LLMs), such as ChatGPT and Bard, have shown potential in various medical applications. This study aimed to evaluate the performance of LLMs, specifically ChatGPT and Bard, in pathology by comparing their performance with those of pathology trainees, and to assess the consistency of their responses. We selected 150 multiple-choice questions from 15 subspecialties, excluding those with images. Both ChatGPT and Bard were tested on these questions across three separate sessions between June 2023 and January 2024, and their responses were compared with those of 16 pathology trainees (8 junior and 8 senior) from two hospitals. Questions were categorized into easy, intermediate, and difficult based on trainee performance. Consistency and variability in LLM responses were analyzed across three evaluation sessions. ChatGPT significantly outperformed Bard and trainees, achieving an average total score of 82.2% compared to Bard's 49.5%, junior trainees' 45.1%, and senior trainees' 56.0%. ChatGPT's performance was notably stronger in difficult questions (63.4%-68.3%) compared to Bard (31.7%-34.1%) and trainees (4.9%-48.8%). For easy questions, ChatGPT (83.1%-91.5%) and trainees (73.7%-100.0%) showed similar high scores. Consistency analysis revealed that ChatGPT showed a high consistency rate of 80%-85% across three tests, whereas Bard exhibited greater variability with consistency rates of 54%-61%. While LLMs show significant promise in pathology education and practice, continued development and human oversight are crucial for reliable clinical application.
The utility of the mHAI scoring system in pediatric autoimmune hepatitis diagnosis and its association with treatment response
Chen W, Noel G, Amin M and Chen F
Autoimmune hepatitis (AIH) is a chronic inflammatory autoimmune disease with either acute or chronic presentation. Previous scoring systems have primarily focused on chronic hepatitis, but none have been validated in an acute setting of pediatric patients. This study aimed to: 1) summarize the clinicopathologic characteristics of pediatric AIH patients; 2) assess if the modified Hepatic Activity Index (mHAI) can be used in both acute and chronic presentations of pediatric AIH; 3) evaluate the association of initial mHAI scores with treatment response at various endpoints. Thirty-one pediatric AIH patients were categorized into acute and chronic presentation groups. Biopsies were reviewed using the mHAI grading and staging system. AIH treatment endpoints were analyzed: 4 weeks (response vs. non-response), 6 months (complete vs. insufficient response), and approximately 12 months (histological remission vs. non-remission). Patients with acute AIH had higher mean mHAI scores and more prominent interface activity. Those achieving complete response at 6 months had significantly higher mean mHAI scores compared to those with an insufficient response. Notably, patients demonstrating fibrosis reversal at the 1-year follow-up often had higher initial mHAI scores. The mHAI can be used to evaluate acute and chronic presentations of pediatric AIH. Acute pediatric AIH has a higher mHAI score with more severe activity. The patients with a higher mHAI have a greater likelihood of achieving a complete response to treatment at 6 months and subsequent improvement in fibrosis status.
Clinicopathological characteristics of extranodal Rosai-Dorfman disease: A retrospective case series of 25 patients
Tran PTC, Din NU, Xu Z and Ahsan BU
Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis, classically affecting the lymph nodes. Even rarer extranodal disease is diagnostically challenging due to overlapping histologic features with other entities and lack of a universally agreed set of biomarkers. Cyclin D1 immunohistochemistry (IHC) may serve as a useful adjunct in diagnosing extranodal RDD. We present a retrospective case series of patients diagnosed with extranodal RDD between January 2013 and December 2023. IHC staining for cyclin D1 was performed on archived tissue samples. Baseline IHC results for biomarkers supporting the RDD diagnosis were recorded along with patient demographic characteristics, clinical features, and disease outcomes. A total of 25 patients with extranodal RDD were included: 21 women (84 %) and 4 men (16 %). The mean age at diagnosis was 42.6 years. Cutaneous and deep tissue involvement was seen in 5 (20 %) and 20 (80 %) patients, respectively. 11 patients (44 %) had disease localized to the trunk and extremities, and 13 had disease in the head and neck region (52 %), of which 5 occurred in the nose and paranasal tissues. Available follow-up data showed most patients fully recovered (n = 11; 78.6 %). However, 1 patient had disease recurrence, 1 developed blindness, and 1 developed deafness. Cyclin D1 IHC was positive in all samples (100 %), consistent with previous studies. The clinicopathologic findings in this study highlight the spectrum of potential disease sites, possible morbid outcomes related to disease site, and the diagnostic utility of cyclin D1 IHC.
Gelatinous transformation of bone marrow associated with ring sideroblasts: A diagnostic pitfall
Hussain M, Rawas F, Gosnell J, Medeiros LJ and Lyapichev KA
Gelatinous bone marrow transformation (GBMT) is a rare condition characterized by adipocyte atrophy, deposition of extracellular gelatinous substance in the bone marrow and associated hypoplastic hematopoiesis. The underlying pathogenic mechanisms of GBMT remain poorly understood. Here we describe 3 cases of GBMT associated with ring sideroblasts. An electronic search of institutional archives was conducted via the laboratory information system to identify patients with a body mass index (BMI) of <18.5 who underwent bone marrow evaluation. The slides and reports for these bone marrow specimens were reviewed. Bone marrow specimens of 10 patients were identified and reviewed. Three (30 %) were found to have GBMT and ring sideroblasts, ranging from 2 to 20 %. Blasts were not increased and there was no other morphologic evidence of dysplasia. Every patient had one or more peripheral blood cytopenias. In one patient, copper deficiency was proven providing an explanation for the ring sideroblasts. To the best of our knowledge, ring sideroblasts have not been well documented in GBMT and aims to contribute to a better understanding of disease recognition and pathogenesis and also to prevent potential misdiagnosis as a myelodysplastic syndrome.
The usefulness of evaluating PTEN expression for accurate grading of phyllodes tumors
Kim D, Suh KS, Kim MR and Choi SY
Phyllodes tumors (PTs) are classified as benign, borderline, or malignant based on histologic characteristics. However, because histological criteria are subjective and diagnosis requires integrating multiple findings, discrepancies often occur between observers. Therefore, it is necessary to discover biomarkers based on the molecular characteristics of PTs. This study aimed to identify dysregulated microRNAs (miRNAs) in PTs through miRNA profiling and determine whether expression of their target genes could be useful as PT biomarkers. MiRNA profiling was performed on 13 PTs (three malignant, three borderline, seven benign) and six fibroadenomas, and predicted target genes of dysregulated miRNAs were selected using three computation algorithms. The expression of two miRNAs, miR-155 and miR-200c, was 1.69-fold and 1.61-fold higher, respectively, in borderline and malignant PT groups than in the benign PT group (p < 0.05). KEGG pathway analysis revealed that the 374 target genes of these two miRNAs (miR-155 and miR200c) participated in several signaling pathways, adherens junction, cell cycle, and pathway in cancer. Immunohistochemical staining for PTEN, one of candidate target genes of miR-200c, was performed on whole slides of PT tissue classified as malignant (n = 9), borderline (n = 12), or benign (n = 21). Stromal tumor cells of high-grade PTs (borderline and malignant) had significantly lower PTEN expression than those of low-grade PTs (benign) (p-value ≤0.001). Semiquantitative analysis of PTEN expression, score 0-8, revealed that it correlated with histologic findings. Low PTEN expression (s-score of 6 or less) was used as a diagnostic criterion for high-grade PTs, it showed 100 % sensitivity and 95.2 % specificity in 42 cases of PTs. Currently, PT grading based solely on subjective histologic findings is challenging, but semiquantitative PTEN expression analysis could provide a more accurate and objective way to grade PTs.
Clinicopathologic features and tumor immune microenvironment of lymphocyte-rich hepatocellular carcinoma
Zhang YW, Zhao C, Su BJ, Lin WZ, Liu WM, Liang J, Shao CK, Cheng N and Chen JN
Lymphocyte-rich hepatocellular carcinoma (LR-HCC) is a rare variant of HCC characterized by pronounced lymphoid infiltration, providing an opportunity to explore the tumor immune microenvironment (TIME) and its potential impact on disease progression and therapy. This study aimed to describe the clinicopathological features and TIME components of LR-HCC to inform more effective treatment strategies. In this study, we present five novel cases of LR-HCC alongside a comprehensive retrospective analysis of 136 previously documented cases. Immunohistochemical evaluation was utilized to systematically assess TIME components and immune checkpoint inhibitor (ICI) targets. Our findings demonstrated a significant predominance of CD3+ T cells over CD20+ B cells (1.5:1, P < 0.001) and a higher frequency of CD8+ cytotoxic T cells compared to Foxp3+ regulatory T cells (2.4:1, P < 0.001), indicating an immune landscape potentially favorable for immunotherapeutic interventions. Programmed cell death ligand 1 (PD-L1) expression was detected in three out of five cases using the VENTANA SP263 assay, suggesting potential responsiveness to ICIs. A pooled analysis of 38 cases showed a 5-year overall survival rate of 73.6 %, which is notably lower than previously reported rates (>90 %), with 29.4 % of patients experiencing postoperative recurrence or lymph node metastasis. Multivariate analysis identified tumor size as an independent predictor of overall survival. These findings emphasize the relevance of TIME characteristics in understanding LR-HCC and point to promising avenues for targeted and immune-based therapies, contributing to the optimization of clinical management for this distinct cancer subtype.
Metastatic tumours to the parotid: A 20-year single institutional experience with an emphasis on 14 unusual presentations
Tsang PPM, Gupta G and Mukhopadhyay S
The parotid gland is a rare site for distant metastasis. We aim to provide an overview of metastatic tumours to the parotid over the past 20 years, focusing on clinicopathological analysis of 14 rare diagnoses. To the best of our knowledge, we are the first group to present the most up-to-date and largest case series on unusual metastases to the parotid. A total of 93 metastatic cases were identified from 2004 to 2023, on the pathology information system at North West London Pathology, with squamous cell carcinoma (n = 45, 48.4 %) as the most common primary, followed by malignant melanoma (n = 29, 31.2 %) and Merkel cell carcinoma (n = 4, 4.3 %). We came across 14 rare tumours that had metastasised to the parotid, including metastatic adenocarcinoma from kidney (n = 3, 3.2 %), lung (n = 3, 3.2 %) and breast (n = 1, 1.1 %), olfactory neuroblastoma (n = 3, 3.2 %), soft tissue sarcoma (n = 2, 2.2 %), small cell carcinoma (n = 1, 1,1 %) and hidradenocarcinoma (n = 1, 1.1 %). Half of all secondary neoplastic lesions (50.5 %) were found in intra-parotid nodes, while the other half (49.5 %) were found in parotid parenchyma. Our study offers valuable insights into the various tumour types that can metastasise to the parotid across a wide age range. It underscores the necessity of maintaining a broad differential diagnosis. Keeping an open mind regarding the potential primary sources of the tumour is imperative for accurate diagnosis and effective treatment planning.
Histomorphology based prediction of p16 immunopositivity and p16/HPV DNA co-positivity in oral squamous cell carcinoma
Naz F, Tanveer N, Verma H, Arava S, Kakkar A, Pandey S, Goel H, Ranjan A, Chopra A and Tanwar P
The histomorphological features predictive of p16 and human papilloma virus (HPV DNA) positivity in oropharyngeal carcinoma have been a matter of much debate. However, only few studies have been done on oral squamous cell carcinoma (OSCC) to correlate the histomorphological features with p16 and HPV DNA positivity. Oral squamous cell carcinoma has distinct etiopathogenesis, treatment and prognosis as compared to oropharyngeal carcinomas. A total of 800 oral squamous cell carcinoma biopsy cases were evaluated for features suggestive of HPV infection like basaloid appearance, absence of stromal reaction, nests and lobules of tumor cells with pushing borders, central necrosis, lympho-epithelial morphology, koilocytes, and non-keratinizing or hybrid morphology. Immunohistochemistry was performed for p16 expression (E6H4 clone, CINtec histology, Roche diagnostics). The cases which showed 2+/3+ (from moderate to high intensity) staining with >75 % cells were considered as p16 immunopositive. All the p16 immunopositive cases were subjected to real-time PCR (polymerase chain reaction) for HPV DNA detection to confirm HPV positivity. A total of 139 (17.37 %) OSCC cases were p16 immunopositive and out of these 104 (104/139, 74.8 %) cases showed HPV-DNA PCR positivity. None of the features were found to be predictive on multivariate logistic regression analysis. However, on bivariable analysis, nest/lobule with pushing border was the only histopathological feature which had a significant correlation with p16 immunopositivity (P value = 0.0001) and p16 and HPV DNA copositivity (P value = 0.0001). (Fisher's exact test -two tailed). To conclude-morphology is not really predictive of HPV positivity in OSCC cases. Only one feature- nests and lobule with pushing border is suggestive on bivariable analysis.
Prognostic significance of CD3+ and CD8+ T-cells immunoscore in renal cell carcinoma: A comparison between two simple models for assessment
Elwy AE, Nassar MI, Shaban SH and Elsaba TM
The immunoscore (ISc) has been extensively investigated as a prognostic indicator for numerous solid tumors. In renal cell carcinoma (RCC), its prognostic significance has been evaluated in a small number of studies. This study was designed to ascertain the prognostic value of ISc based on CD3+ and CD8+ T cells in patients with RCC. This study included 115 non-metastatic RCC patients who underwent nephrectomy. The ISc was obtained by estimating the densities of CD3+ and CD8+ cells at the invasive margin and center of the tumor using two methods: cell count per square millimeter (cell count/mm) and percentage of cells per square millimeter (% of cells/mm). The patients were categorized into low and high groups according to the ISc. The associations between the ISc and clinicopathological characters, including survival, were analyzed statistically. Adverse clinicopathologic factors were significantly associated with high ISc. Patients with high ISc had significantly worse overall survival (OS) and disease-free survival (DFS) rates over three years (p < 0.001). High ISc was considered a predictor of shortened DFS in univariate analysis (p < 0.001). However, in multivariate analysis, it was a dependent predictor. High ISc could help identify individuals more likely to develop recurrence and may impact treatment strategy for more effective personalized care. Moreover, establishing a modified objective, automated, digital quantification method of immune cells (% of cells/mm instead of cell count/mm) is expected to be simple to implement in routine, highly affordable, time efficient, clinically meaningful, and will improve assay performance.
Clinicopathological analysis of primary central nervous system lymphoma in patients with or without HIV infection
Li M, Chen J, Wang P, Feng E, Chen X, Gao H, Ma Z and Zhou X
The clinicopathological features of HIV-related primary central nervous system lymphoma (PCNSL) and immunocompetent primary central nervous system lymphoma (IC-PCNSL) were found to be distinct. Thirty-seven patients with HIV-related PCNSL and thirty patients with IC-PCNSL were included in our study. Hematoxylin & eosin (HE) staining, immunohistochemical detection using CD10, MUM1, CD20, Bcl-2, Bcl-6, p53, C-MYC, Ki67, methyltransferase like factor 3 (METTL3) antibodies and Epstein-Barr encoding region (EBER) in situ hybridization were performed. All of the patients were classified as the diffuse large B-cell lymphoma (DLBCL) histological type. Patients with HIV-related PCNSL were younger and more likely to be male, with elevated lactate dehydrogenase (LDH) and low sugar content in cerebrospinal fluid (CSF) compared to patients with IC-PCNSL.The positive rates of METTL3, Bcl-2, p53 and EBER were significantly higher in HIV-related PCNSL patients than in IC-PCNSL patients. Furthermore, we also found that the expression of METTL3 was lower in germinal centre B-cell (GCB)-like DLBCL (n = 7) than in non-GCB like DLBCL (n = 30) in HIV-related PCNSL (P = 0.030); however, in IC-PCNSL patients, the expression of METTL3 was not significantly different between GCB-like DLBCL and non-GCB-like DLBCL (P = 0.670). Although the manifestations are similar in PCNSL patients with and without HIV, HIV-related PCNSL differs from IC-PCNSL in terms of pathological characteristics including METTL3, Bcl-2, p53 and EBER. We therefore suggest that the pathogenesis of HIV-related PCNSL and IC-PCNSL may differ according to host immune status.
Prognostic impact of EGFR expression and immunohistochemistry-based "molecular classification" in bladder cancer
Ozsagir YO, Ozsagir E, Dil E, Eren H, Aydin Mungan S and Bedir R
Recent genomic studies emphasize the necessity of molecular classification to reflect diverse clinical and pathological characteristics of bladder cancer. Immunohistochemically bladder cancer can be classified into molecular subtypes, including basal, luminal, and p53-like subtypes. Epidermal growth factor receptor (EGFR) is frequently expressed in basal-type bladder cancers and is associated with poor prognosis. In our study, 88 urothelial carcinoma cases were retrospectively analyzed, molecularly subtyped using CK5/6, GATA3, p16 immunohistochemistry and examined for EGFR expressions as well as clinical and histopathological features. Tumor cell scores ≥20 % considered positive, classifying cases as luminal (GATA3-positive), basal (CK5/6-positive), double-positive (both-positive), or double-negative (both-negative). Further division of luminal and basal cases was based on p16 status: luminal-p53 or basal-p53 (p16-positive) and luminal-non-p53 or basal-non-p53 (p16-negative). Among the cases, 4 (4 %) were double-negative, 48 (55 %) luminal-non-p53, 21 (24 %) luminal-p53, 5 (6 %) basal-non-p53, 3 (3 %) basal-p53, and 7 (8 %) double-positive. Our findings revealed that basal-non-p53 type bladder cancer is associated with poor prognosis, muscle invasion, and high-grade cytology. Basal-p53 and double-negative types exhibited less aggressive features compared to basal-non-p53 types, with associations observed with lamina propria invasion and high-grade cytology. Luminal-p53 type demonstrated higher recurrence rates. Luminal-non-p53 type displayed the least aggressive characteristics, often associated with papillary histopathology. EGFR expression was found to be high in basal-non-p53 type and was further correlated with adverse prognostic indicators, lamina propria invasion, and high-grade cytology. The identification of molecular subtypes and EGFR expression through immunohistochemistry, alongside traditional bladder cancer classifications, enhances tumor behavior prediction and supports effective clinical management.
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Prevalence, cyto-histo correlation, and molecular and ultrasonographic profile
Xu Z, Vitale A, Keller C, Alkhoory W, Zhang Z and Yuan L
Non-invasive follicular thyroid neoplasm with papillary like nuclear features (NIFTP) was introduced in 2017 WHO Classification of Endocrine Tumors. In this study, we aim to characterize the molecular and ultrasonographic profiles of NIFTP and evaluate the performance of fine needle aspiration (FNA) cytology. Consecutive thyroid resections at our institution between 2018 and 2022 were collected; 1282 thyroid resections were identified. NIFTP was diagnosed in 109 cases (prevalence: 8.5 %); 65 (60 %) were the targeted nodules with an average size of 2.5 cm. Among these 65 targeted, 27 had Afirma testing results, 44 had Thyroid Imaging Reporting and Data System (TIRADS) scores, and 53 had FNA results. Of the 27 cases with Afirma reports, 23 were labeled "suspicious", including 5 with RAS-related mutations (risk of malignancy (ROM) 75 %) and 17 without a reportable genetic alternation (ROM 50 %). 60 % cases with TIRADS scores were classified as TIRADS 4, while 16 % were classified as TIRADS 5. The majority of the 53 FNA cases had a diagnosis of AUS/FLUS (53.7 %) or FN (31.5 %). One additional targeted nodule with a diagnosis of NIFTP had BRAFV600E mutation and was reclassified as papillary thyroid carcinoma. In summary, the majority of the targeted NIFTPs had "suspicious" Afirma testing results (85 %), TIRADS 4 scores (60 %) and either AUS/FLUS (53.7 %) or FN (31.5 %) FNA results. The sensitivity and specificity of cytology for diagnosing NIFTP were 90 % and 57 %, respectively, with a positive predictive value (PPV) of 16 % and negative predictive value of 98 %.
Superficial ALK-rearranged myxoid spindle cell neoplasms: Clinicopathologic and molecular analysis of two cases and a review of the literature
Luo W, Zheng J, Hei M, Jiang Y and Su B
Superficial anaplastic lymphoma kinase (ALK)-rearranged myxoid spindle cell neoplasms are a recently identified subtype of cutaneous soft tissue tumors, distinct for their co-expression of CD34 and S100 and characterized by ALK gene rearrangements. Although 72 cases have been reported primarily as isolated case reports, this tumor subtype has yet to be included in the WHO classification of soft tissue tumors, underscoring the need for further study. In this study, we diagnosed two additional cases, both arising in the dermis and subcutaneous tissue. These tumors exhibited characteristic pathological features, including linear or concentric whorl patterns, prominent myxoid and collagenized stroma, mild cellular atypia, and rare mitotic activity. The presence of infiltrative margins and the potential for recurrence after surgery suggest at least locally aggressive clinical behavior. Immunohistochemically, the tumors diffusely expressed S100 and CD34, with strong ALK-D5F3 positivity, confirmed by ALK gene rearrangement. These findings further expand the clinical and pathological spectrum of ALK-rearranged neoplasms and highlight the need for continued research on their biological behavior and classification.
TRPS1 expression in cytologic specimens of salivary duct carcinoma and other salivary gland tumors
Wang M, Cai G and Gilani SM
Recent studies suggest that trichorhinophalangeal syndrome type 1 (TRPS1) is sensitive immunomarker for breast carcinoma (BC). Salivary duct carcinoma (SDC) of salivary gland can share similar morphologic and immunophenotypic features with BC. This study aimed to assess the expression of TRPS1 in SDC and other salivary gland tumors (SGTs). Cytology cases and selected surgical specimens of SGTs were retrieved. Forty-three cases were selected and TRPS1 immunohistochemistry (IHC) was performed on cell blocks and some histologic specimens. Of those 43 cases, all 13 SDC cases showed TRPS1 expression except for one case. The remaining 30 cases include pleomorphic adenoma (n = 7), Warthin tumor (n = 4), basal cell adenoma (n = 3), adenoid cystic carcinoma (n = 2), secretory carcinoma (n = 5), mucoepidermoid carcinoma (n = 4), and acinic cell carcinoma (n = 5). Three of thirty cases were negative for TRPS1 while the remainder showed variable expression of TRPS1 ranging from focal weak to diffuse strong staining. The three negative cases include a case of secretory carcinoma, mucoepidermoid carcinoma and Warthin tumor. Our study confirmed that TRPS1 expression is present in SDC and other SGTs, indicating an overlapping immunoprofile with breast cancer. Additionally, it may not help differentiate SDC or SGTs from each other. Further studies with larger cohorts are needed.
FOXP3 expression in duodenal mucosa: Unique role in pathogenesis and differential diagnosis of celiac disease
Yilmaz F and Atay K
Forkhead box protein P3 (FOXP3) positive regulatory T lymphocytes are indispensable in the inflammatory homeostasis of the gastrointestinal tract and represent a significant subset of regulatory cells in inflammatory, autoimmune, and neoplastic conditions. This study aimed to elucidate the potential of FOXP3 expression in diagnosing and pathogenesis of celiac disease (CD) by comparing duodenal biopsies of CD cases with non-CD ones, some of which had increased intraepithelial lymphocytes (IELs). Two hundred sixty-one duodenal tissues of patients who applied to adult gastroenterology were reevaluated for immunohistochemical analysis. After excluding patients on a gluten-free diet (n = 44), the CD (n = 97) and non-CD (n = 120) groups were divided based on clinical complaints that could be associated with CD (intestinal or extraintestinal), serologic and histologic findings. The specific threshold was determined by receiver operating characteristic (ROC) analysis, and its relationship with CD diagnosis and clinicopathological data was evaluated. ROC analysis offered a ">14" cut-off value for diagnosing CD, for which AUC (Area Under The Curve): 0.968, p < 0.0001, sensitivity: 92.8, specificity: 91.7, positive and negative predictive values were 90 % and 94 %, respectively. High FOXP3 expression was associated with higher IEL, diagnosis of CD, more severe histologic (higher Marsh score) and endoscopic (scalloping) findings, and higher anti-tissue transglutaminase and anti-endomysium IgA titers (p < 0.001). It also correlates with IEL in CD patients and is unaffected by the increase in IEL and the presence of gastric Helicobacter Pylori in the non-CD group. FOXP3 is a sensitive and specific marker for diagnosing CD despite inflammatory conditions resulting from non-CD causes.
T-cells are significantly reduced in the luminal gastrointestinal tract of patients with "complete" 22q11.2 deletion syndrome (DiGeorge syndrome): Utilization of chromogenic multiplex immunohistochemistry to define cellular populations
Kwon GJ, Jeck WR, McCall S, Su Z and Pendse AA
Patients with 22q11.2 deletion syndrome or DiGeorge syndrome commonly report gastrointestinal symptoms in addition to more widely understood cardiac and immunodeficiency abnormalities. However, the morphologic features of gastrointestinal tract pathology in these patients are poorly understood. We previously reported that plasma cells are essentially absent from the luminal gastrointestinal tract of patients with "complete" DiGeorge syndrome. Herein, we add to the current understanding of the luminal gastrointestinal tract changes in patients with DiGeorge syndrome. Patients with cytogenetically confirmed DiGeorge syndrome were identified after approval from our institutional review board. Gastrointestinal tract biopsies from patients with DiGeorge syndrome that were severely immunosuppressed (complete DiGeorge syndrome, DGS-I), partially immunocompromised (partial DiGeorge syndrome, DGS), and from control patients were reviewed. Two panels of chromogenic multiplex immunohistochemistry (IHC) were performed to evaluate the immune cell infiltrate in the lamina propria of the duodenum and colon. "Panel #1" was composed of antibodies targeting CD3, CD20, and CD68. "Panel #2" was composed of antibodies targeting CD4, CD8, CD56, and TCRϒδ. Assessment of cell types identified by these antibody targets demonstrated a significant reduction of duodenal and colonic T-cells in patients with complete DiGeorge syndrome. In addition to establishing the morphologic phenotype of the luminal gastrointestinal tract of patients with DiGeorge syndrome, we also highlight our chosen technology of chromogenic multiplex IHC as a relatively accessible research and diagnostic tool with wide potential to be utilized across various disease processes.
PIT-1/SF-1 co-expression in pituitary neuroendocrine tumors (PitNETs) with comprehensive review of the literature: How should we best characterize these neoplasms?
Faraj CA, McCutcheon IE and Gubbiotti MA
The nomenclature and classification of neuroendocrine tumors of the anterior pituitary have undergone significant change over the last few years. Despite the updated classification system as devised by the World Health Organization, some tumors do not fit neatly into the currently defined categories. The most common tumor type not defined by the updated guidelines is a pituitary neuroendocrine tumor with co-expression of SF-1 and PIT-1. In this manuscript, we provide our institutional experience with such unusual cases and combine our findings with those in the available literature to provide the largest, most comprehensive dataset regarding clinical and pathologic information for these unique tumors. Based on our findings, we also propose a classification scheme for pituitary neuroendocrine tumors to integrate lineage, hormonal expression, and clinical function as we believe this constellation of information will best help the clinical teams treating these patients.
PD-L1 (22C3) expression and prognostic implications in esophageal squamous cell carcinoma
Chi Z, Peng L, Karamchandani DM and Xu J
Programmed cell death-ligand 1 (PD-L1) clone 22C3 is the only Food and Drug Administration-approved companion diagnostic test for pembrolizumab for the treatment of esophageal squamous cell carcinoma (ESCC). However, prior studies conducted in Asia and Europe have used various PD-L1 antibody clones other than 22C3. We aimed to study the expression profile of PD-L1, specifically of clone 22C3, in ESCC and its significance with regards to histological features, clinical parameters, and overall survival in a case series from two large US hospital systems. PD-L1 (22C3) immunohistochemistry was performed on 82 specimens obtained from 75 patients. Electronic medical records were reviewed to obtain the clinical and follow-up data. Of these specimens, 39 % (32/82) were negative for PD-L1 (22C3) expression (combined positive score (CPS) of 0). The remaining 50 specimens were positive, with CPSs ranging from 1 to 100. Treated specimens showed decreased PD-L1 (22C3) expression compared to untreated specimens. In the multivariate Cox proportional hazards regression model, PD-L1 (22C3) expression was shown to be a favorable prognostic factor for overall survival (p = 0.03, hazard ratio 0.16) only when the CPSs were ≥ 25, independent of surgery, definitive chemotherapy and/or radiotherapy, immunotherapy, and initial clinical stages. We performed a comprehensive study to investigate the expression profile of PD-L1 clone 22C3 in the US patients with ESCC. Our analysis showed that PD-L1 (22C3) expression decreased in treated specimens, and a CPS of ≥25 was associated with a favorable prognosis.
Poor response of HER2-positive mucinous carcinomas of breast to neoadjuvant HER2-targeted therapy: A study of four cases
Han M, Schmolze D, Arias-Stella JA, Wei CH, Mortimer J and Fan F
Breast mucinous carcinoma (MC) is typically positive for estrogen receptor (ER) and progesterone receptor (PR) expressions and negative for human epidermal growth factor receptor (HER2) overexpression. HER2 positive MC is a rare entity; its response to neoadjuvant HER2-targeted therapy remains unclear.
Diagnostic immunohistochemistry use in Belgian laboratories
de Meester C, Costa E, Schönborn C and San Miguel L
In Belgium, the use of IHC testing has grown in the last decade. However, there is a lack of information on the specific indications for which it is reimbursed. The aim of the study is to offer an overview on the use of diagnostic inmunohistochemistry (IHC) testing and its recent trends.
Most Siewert type II esophagogastric junction adenocarcinomas in Chinese patients lack a Barrett esophagus background
Tan WW, Cheng CS, Wang KX, Lin MX, Liu SX, Kang LL and Zhang HD
The histological origins and classification of Siewert II esophageal gastric junction (EGJ) adenocarcinomas are controversial. While the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system suggests that they be classified as esophageal cancer, some scholars insist that these cancers include a Barrett esophageal (BE) adenocarcinoma form and a gastric adenocarcinoma form. To obtain data relevant to this debate, in this study, a multi-center sample of 25 cases of Siewert II EGJ adenocarcinoma spanning a 6-year period were analyzed. The endoscopic characteristics of the tumor lesions and pathology characteristics of peritumoral mucosal background in biopsies were determined. Cases were classified as esophageal adenocarcinoma if the tumor center was located on the oral side of the EGJ and accompanied by BE. They were classified as gastric adenocarcinoma if the tumor center was located on the anal side of the EGJ and accompanied by atrophic gastritis. Of the 25 cases examined, 20 had evaluable background mucosal data, including 14 (56 %) classified as gastric adenocarcinoma and 3 (12 %) classified as BE adenocarcinoma. The remaining 3 cases (12 %) did not have signs of BE or atrophic gastritis, and thus were not classified. Siewert type II EGJ adenocarcinoma cases in China were found to be heterogeneous, with most cases being consistent with gastric adenocarcinoma. Thus, it would not be reasonable to classify all Siewert type II EGJ adenocarcinomas as esophageal cancer.