Amendments in surgical pathology reports: An 8-year institutional experience.

Surgical pathology reports may undergo revisions broadly categorized as addenda (supplementary information) or amendments (changes to finalized reports). Amendments indicate potential flaws in the diagnostic process and serve as important indicators of vulnerabilities in the histopathology workflow. This study analyzed the frequency and distribution of amendments in surgical pathology reports over 8 years to identify patterns highlighting opportunities for improvement. Surgical biopsies, excisions, and resections were included; cytology and molecular tests were excluded. Amended reports were categorized using previously used taxonomy documented in literature. Defects were classified as misinterpretations, misidentifications, defective specimens, or defective reports. Of 101,355 reports, 155 (0.15 %) were signed out with amendments. The amendment rate was approximately 1-2 cases per 1000 reports annually. Misinterpretations accounted for the majority (52 %) of amended reports, with undercalls (62 %) and overcalls (27 %) being predominant subtypes. Tumor staging was amended in 57 (37 %) cases, with 30 being upstaged and 11 downstaged clinically. The highest number of misinterpretation defects occurred in head and neck (36 %) and breast (21 %) specimens. Misinterpretation defects were present in 53 % of malignant cases versus 42 % of benign cases. In 18 cases, there were significant changes in pathological diagnosis (14 major and 4 minor). A standard taxonomy categorizing report defects is crucial for measuring and improving quality control. Accurate pathology reporting impacts patient care and guides workflow improvements. This taxonomy enables us to track variations and deficiencies in our pathology reporting processes in a reproducible way across the department.

Application of lean methodology to frozen section workflow - An audit of present practices at a single large oncology center.

AIM: We conducted a pilot study to analyze the frozen section workflow in the histopathology department and to construct a future state map using Lean management for a better efficiency. METHOD: We analyzed the current state of frozen section workflow in our department, from receipt of the specimen to delivery of slides to the pathologist to communication of report to the surgeon by using value-stream mapping and spaghetti diagram. Further, with the help of the fishbone diagram and Pareto's chart, root cause analysis was done, and a future state map was created with help of a spaghetti diagram to eliminate the non-value-added steps. RESULTS: Our current value-stream map identified a total specimen processing time of 3393 min of which 2880 min were value-added, translating to a process cycle efficiency of 84.88 %. Also, with the help of tools of lean management we constructed a future state map to improve process cycle efficiency. CONCLUSION: In this study, we have attempted to use a few tools of lean management systems and suggested ways for continuous improvements that can be successfully implemented in histopathology laboratories.

Impact of 2018 ASCO/CAP guidelines on HER-2 reporting categories of IHC and reflex FISH in breast cancer.

Human epidermal growth factor receptor 2 (HER-2) is an established prognostic and predictive biomarker for breast cancer. To ensure accuracy and uniformity for HER-2 testing, ASCO/CAP published guidelines in 2007 which were updated in 2013 and recently in 2018. In this first study from Indian Oncology center, we evaluated the impact of 2018 ASCO/CAP guidelines. We found a substantial decrease in equivocal IHC cases (P-value < .00001). On reclassification, a total of 5.6% cases from equivocal and positive categories (2013 guidelines) shifted to the negative FISH result category (P-value < .0001), with adoption of 2018 guidelines and eliminated the double equivocal cases.

Impact of 2013 ASCO/CAP HER2 reporting guidelines in breast cancer: An assessment study from Indian oncology centre that primarily performs HER2 IHC testing with special emphasis on IHC equivocal category.

The ASCO/CAP guidelines for HER2 reporting in breast cancer published in 2007 and were updated in 2013 to assure that the right patient receives the targeted therapy. The updated guidelines have lowered the threshold for HER2 positivity criteria and altered the equivocal category for both IHC and FISH. This first study from India addresses the impact of these updated guidelines in the various reporting categories at a tertiary care centre. We compared the trend of HER2 IHC reporting 1 year before (Period A) and 1 year after (Period B) the implementation of updated 2013 ASCO/CAP guidelines. All HER2 equivocal IHC cases of post 2013 guidelines were reclassified as per 2007 guidelines to detect additional number of cases that have been put into equivocal category. Reflex FISH correlation was also assessed to detect any additional cases eligible for anti HER2 therapy with implementation of these updated guidelines. With implementation of updated 2013 guidelines, there was significant decrease in the number of cases scored as 1+ (from 30.7% to 20.6%; P value: .0001) while significant increase in number of 2+ cases (from 20.2% to 27.3%; P value: .004). Post 2013 guidelines, 39% (64 cases) of tumors were additionally put into the equivocal category which would have been considered as negative (score 1+) as per 2007 guidelines. The reflex FISH testing in these equivocal cases resulted in detection of only 1.5% of additional cases eligible for anti HER2 therapy. With implementation of updated 2013 guidelines, there is no significant increase in HER2 positivity trend. However, there is appreciable increase in IHC equivocal cases which subsequently led to increased reflex FISH testing without significantly contributing to the detection of additional eligible cases for anti HER2 therapy, but resulted in delaying of definite HER2 status along with financial implications.

Adrenal ganglioneuroma with retroperitoneal lymph node metastasis: A rare scenario.

ABSTRACT: Ganglioneuroma (GN) is the most differentiated and benign variant of neuroblastic tumors, most commonly located in the posterior mediastinum, followed by the retroperitoneum and adrenal gland. Children of <10 years of age are more commonly affected than adults. Though benign, GNs can very rarely metastasize to regional lymph nodes or distant sites like liver, bone, spleen, and soft tissues. Metastatic lesions are assumed to represent neuroblastomas in which the metastasis and the primary tumor, both have matured. This differentiation can occur spontaneously or after treatment. We present a primary ganglioneuroma of adrenal gland in a 4-year-old child with nodal metastasis, without any blastemal component at any site.

FH deficient uterine leiomyomas-a case series.

Introduction: Fumarate hydratase (FH) deficient uterine leiomyomas account for only 0.4 % of all uterine leiomyomas. They are characterized by some distinct histological features and may be associated with Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Methods: Herein we present a series of five cases of FH deficient uterine leiomyomas in patients with a mean age of 30 years. All five patients underwent myomectomy. Three of these cases had an outside histopathologic diagnosis ranging from Smooth muscle tumor of uncertain malignant potential (STUMP) to Leiomyosarcoma while two cases were operated at our centre. All five cases were reported as suggestive of FH deficient leiomyomas and were advised germline testing along with genetic counselling. Results: Immunohistochemically four of the cases showed moderate to strong positivity for 2-SC with a complete loss or reduced expression of FH while one case showed absence of 2-SC staining. Discussion: Mutations in FH lead to reduced enzyme activity and accumulation of fumarate leading to a complete loss or aberrant reduced expression seen on immunohistochemistry, which confirms the diagnosis. It is important to differentiate it from a leiomyosarcoma or other malignant spindle cell tumors as these tumors follow a benign course. Their association with HLRCC also needs to be established for a suitable follow up since HLRCC-associated RCCs are often aggressive. Conclusion: Management of such leiomyomas is myomectomy or hysterectomy with advice of genetic testing to rule out HLRCC. Histomorphology and immunohistochemistry are imperative for a correct and timely diagnosis.

Diagnostic utility of LMO2 immunohistochemistry in distinguishing T-lymphoblastic leukemia/lymphoma from thymoma.

Distinguishing T-lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) from thymomas (especially B1 or B2 type) can be challenging particularly in limited trucut biopsy material where appreciating architecture is difficult or the background epithelial component does not provide tangible evidence for definite diagnosis. As a pathologist, it is important to accurately diagnose these neoplasms because they have entirely distinct management protocols. Recent studies have reported that LIM Domain Only 2 (LMO2) is expressed in neoplastic lymphoblasts of T-ALL/T-LBL and is absent in thymocytes of normal thymuses or thymomas. An observational study was done to test the sensitivity and specificity of LMO2 in differentiating neoplastic lymphoblasts from thymocytes of thymomas/normal thymuses. Our study showed that LMO2 had sensitivity of 70% and specificity of 100% in diagnosing LBL. None of the thymomas (B1 or B2 type) showed expression of LMO2 in the neoplastic cells. LMO2 is a reliable marker of transformed T-cell precursors and should be routinely included in immunohistochemical panel when evaluating thymic/mediastinal neoplasms.

Extranodal follicular dendritic cell sarcoma presenting as colonic mass: A diagnostic and therapeutic challenge.

Folliclular dendritic cell sarcoma (FDCS) is an extremely rare neoplasm originating from folliclular dendritic cells, both nodally and extranodally. Its primary presentation as a large colonic mass is rare and can be misdiagnosed as epithelial tumor/soft tissue tumor both clinically and through histomorphology. Due to its rarity and limited consensus guidelines about its management, it presents as a diagnostic and therapeutic challenge for pathologists and oncologists. However, accurate diagnosis is imperative due to its distinct prognostic and therapeutic implications. Herein we report, two cases of extranodal FDCS of colon with the aim of contributing to the management of this uncommon entity.

Fumarate hydratase-deficient renal cell carcinoma: an oncology care institutional experience.

Renal cell carcinoma (RCC) accounts for 2% of all cancer cases worldwide, and majority are sporadic. The latest World Health Organization (WHO) classification of renal cell tumors (fifth edition, 2022) has molecularly defined renal tumor entities, which includes fumarate hydratase (FH)-deficient RCC. FH-deficient RCC is an aggressive carcinoma caused by pathogenic alterations in FH gene, seen in 15% of patients with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) syndrome. These tumors occur more frequently at a younger age and present at an advanced stage, carrying a dismal prognosis. We report a series of 10 cases of FH-deficient RCC. The mean age was 49.8 years, and all cases presented in advanced stages (III and IV). Morphologically, the cases had varied architectural patterns with characteristic eosinophilic macronucleoli and perinucleolar halo. On immunohistochemistry (IHC), all showed diffuse nucleo-cytoplasmic expression of S-(2-succino)-cysteine (2-SC), with loss of FH in seven cases. FH-deficient RCCs are aggressive neoplasms and can be diagnosed using specific IHC markers (FH and 2-SC). These patients should undergo germline testing for FH gene mutation, genetic counseling, and surveillance of family members.

Evaluation of Turnaround Times of Diagnostic Biopsies: A Metric of Quality in Surgical Pathology.

Introduction. Timely and accurate diagnosis of diseases is crucial for effective patient care. Turnaround time (TAT) in surgical pathology, defined as the time between accessioning the sample and reporting results, is a key performance indicator reflecting quality and efficiency. This study explores factors affecting TAT for diagnostic biopsies in a tertiary oncology hospital. Methods. A 1-month pilot study was conducted, focusing on 695 in-house diagnostic biopsies. Biopsies were categorized as routine (requiring only hematoxylin and eosin (H&E) staining) or complex cases (requiring additional tests). TAT was defined as the time between sample accessioning and report availability in the electronic medical record, with delays defined as exceeding 3 days for routine cases and 4 days for complex cases. Survival analysis using Kaplan-Meier plots was utilized to analyze TAT. Results. The overall mean TAT was 3.7 ± 2 days, with routine cases at 3.1 ± 2 days and complex cases at 4.8 ± 2 days (P < 0.001). Survival analysis revealed prolonged TAT for complex cases. Organ-specific analysis highlighted variations in TAT, with brain biopsies presenting the highest complexity and longest TAT. Surprisingly, malignant cases demonstrated slightly shorter TATs compared to benign cases (P = 0.026). Delays were observed in 34% of all cases. Conclusions. Laboratory TAT is crucial and is frequently used as a performance benchmark. We analyzed the various causes of delayed TAT in our hospital's histopathology department, with an emphasis on variables in the analytical phase. The results of this study demonstrate that cases involving ancillary techniques had significantly longer TATs compared to routine H&E cases.

Metastatic choriocarcinoma of the kidney in the absence of existing primary uterine tumor: A rare presentation.

Gestational choriocarcinomas are malignant neoplasms generally arising in the uterus in women of childbearing age. These are aggressive tumors with a high incidence of metastasis to vascular organs such as the lung, liver, and brain. Renal metastasis is extremely rare with low incidence rate and very few cases have been reported in literature. Hereby, we report a rare case of metastatic choriocarcinoma to the kidney in a 29-year-old female 10 years after resection of a hydatidiform mole. The histopathological diagnosis was made on a nephrectomy specimen. Pelvic and abdominal scan did not show any abnormal radiological findings. She was started on first-line chemotherapy and showed a complete response. In conclusion, gestational or primary nongestational choriocarcinomas should always be considered as a differential diagnosis in young females of reproductive age group presenting with flank abdominal pain, unexplained hematuria, and atypical renal tumor histology.

Myeloid sarcoma presenting as nasopharyngeal mass: A rare clinicopathological scenario.

Myeloid sarcoma (MS) is considered as an extramedullary manifestation of acute myeloid leukemia (AML) with or without concurrent AML. It can present at any age and any site, however, nasopharynx being an extremely rare site of manifestation. MS may precede AML by weeks, months or years, thereby necessitating an early diagnosis and timely intervention and treatment. We report a case of MS in a young female who presented with nasal obstruction and epistaxis for 3 months. The present case also highlights the significance of judicious use of immunohistochemistry panel while dealing with a hematolymphoid neoplasm devoid of expression of B-cell or T cell specific markers in head and neck region.

Primary pulmonary NUT midline carcinoma: An elusive and a rare diagnostic entity.

Nuclear protein in testis (NUT) midline carcinoma is a poorly differentiated tumor, is more common in midline anatomic sites, and involves young adults and children mainly. Primary pulmonary NUT midline carcinoma (NMC) is a rare and poorly defined entity in the prevailing literature. Being a highly aggressive and fatal neoplasm, it gets incumbent for the oncologists and the pathologists to be aware of this entity as it holds distinct management protocol and prognosis. Currently, BET inhibitors (BETi) and histone deactylase inhibitors have shown promising results as targeted therapies in clinical trials in head and neck NMC. We present a case report of NMC of primary pulmonary location in a young male with widespread bony metastasis.

Correlation NKX2.2 IHC and EWSR1 break-apart FISH in the diagnosis of Ewing sarcoma: Can combined NKX2.2 and CD99 immunoexpression obviate or minimize the need of FISH testing? First assessment study from Indian tertiary cancer care center.

Context: Ewing sarcoma (ES) are malignant small round cell tumors (MSRCT) characterized by rearrangements of EWSR1 gene. Although gold standard for diagnosis is detection of specific fusion genes by molecular testing, these ancillary tests are costly and only available in limited number of settings. There is a persuasive evidence for reliability of NKX2.2 immunohistochemistry (IHC) as a surrogate marker for EWSR1 gene rearrangement in ES. Aims: The aim of this study is to correlate the NKX2.2 immuno-expression with genetically confirmed ES cases and also to assess the reliability and accuracy of NKX2.2 along with combined positivity of NXX2.2 and CD99 in diagnosing ES and differentiating it from other relevant histological mimics. Settings and Design: The present study is a retrospective study conducted over a period of 6-year duration in a tertiary cancer care center. Methods and Material: We evaluated NKX2.2 immunoexpression in 35 genetically confirmed cases of ES and also in pertaining differential entities (n = 58) of ES including rhabdomyosarcoma (n = 20), lymphoblastic lymphoma (n = 14), Wilms tumor (n = 10), poorly differentiated synovial sarcoma (n = 4), small-cell osteosarcoma (n = 4), neuroblastoma (n = 5), and mesenchymal chondrosarcoma (n = 1). CD99 was performed in the category of MSRCTs showing NKX2.2 positivity to evaluate combined specificity for the diagnosis of ES. Results: Of the 35 genetically confirmed cases of ES, 29 cases (83%) showed NKX2.2-positive expression (83% sensitivity). Compared to ES, NKX2.2 was positive in only 05% cases (3/58 cases) of non-ES MSRCT. Only two of five cases of neuroblastomas and one case of mesenchymal chondrosarcoma showed NKX2.2 positivity. CD99 positivity was seen in 100% of ES and in the single case of mesenchymal chondrosarcoma. All five cases (100%) of neuroblastoma were negative for CD99. Conclusions: The presented study, which is the first from an Indian oncology center, showed NKX2.2 IHC is quite reliable in diagnosis of ES in the right clinicopathological context. With remarkable sensitivity and specificity of NKX2.2 IHC for diagnosis of ES, we propose that combined positivity of CD99 and NKX2.2 IHC can obviate or minimize the need of EWSR1 gene rearrangement molecular testing for diagnosis of ES.

Bilateral, multicenteric metanephric adenoma associated with Wilms' tumor in a child: a rare presentation with important diagnostic and therapeutic implications.

Metanephric adenoma is an uncommon benign renal tumor that occurs predominantly in adult females and rarely in children. On histomorphology it shows a resemblance to Wilms' tumor, nephrogenic rests and papillary renal cell carcinoma. Multifocality along with multicentricity has not been documented in English literature till date. From a diagnostic and therapeutic viewpoint, recognition of this entity is of the utmost importance, because it shows a favorable clinical outcome. We describe a rare case of bilateral, multicentric metanephric adenoma associated with triphasic Wilms' tumor (stage II) of the left kidney in a male child.

High Grade Myoepithelial Carcinoma of Maxillary Sinus with Extensive Rhabdoid Differentiation and INI-1 Loss: Expanding the Histopathological Spectrum of Sinonasal Carcinoma.

Myoepithelial carcinoma (MEC) of salivary gland is an uncommon tumor with no specific age or sex predilection. Most of the cases (~90%) arise in parotid and submandibular glands followed by palate. MEC of maxillary sinus is rare. We describe an extremely rare case of high grade MEC with rhabdoid differentiation and INI-1 loss involving maxillary sinus of an elderly male.

Treatment conundrums in osteosarcoma of the breast: Case report of two cases from a tertiary care cancer center in India.

Extraosseous sarcoma of the breast is an infrequent entity and a harbinger of poor prognosis. Histogenesis of this tumor is uncertain, and it can arise both in denovo and metastatic settings. Morphologically, it is indistinguishable from its skeletal counterpart and clinically, it presents like any other subtype of breast cancer. Tumor recurrence with a propensity for hematogenous rather than lymphatic spread plagues with this malicious disease. Treatment guidelines are mainly extrapolations from those of treatment of other extra-skeletal sarcomas as literature is limited in this context. In this study, it was aimed to present two clinical cases with similar clinical profiles and different treatment outcomes. The intent of this case report is to contribute to the limited database available for management of this rare disease.

Analysis of Spatial Heterogeneity of Responses in Metastatic Sites in Renal Cell Carcinoma Patients Treated with Nivolumab.

Background: The purpose was to determine whether tumor response to CPI varies by organ and to characterize response patterns in a group of surgically treated metastatic RCC patients treated with Nivolumab. Methods: A retrospective analysis was undertaken between January 2016 and March 2020 on patients receiving Nivolumab for metastatic RCC, following first-line therapy and having at least one baseline and two follow-up scans. A Fisher's exact test was used to compare categorical variables, and a Kruskal-Wallis test was used to compare continuous variables. Results: Twenty-one out of thirty patients evaluated were eligible, and they were divided into two groups: responders (n = 11) and non-responders (n = 10). According to all iRECIST standards, 18 (85.7 percent) of the 21 patients had PD (10 patients), PR (3 patients), or SD (8 patients). At baseline, 7, 15, 4, 13, 7, and 7 patients, respectively, had detectable hepatic metastasis and lung, brain, lymph node, soft tissue, and other intra-abdominal metastases; these patients were evaluated for organ-specific response. The ORRs for hepatic metastasis and lung, brain, lymph node, soft tissue, adrenals, and other intraperitoneal metastases were correspondingly 10%, 20%, 35%, 0%, and 25%. In total, 13 (61.9%) of them demonstrated varied responses to CPI therapy, with 6 (28.5%) demonstrating intra-organ differential responses. The lymph nodes (35%) had the best objective response (BOR), followed by the adrenals and peritoneum (both 25%), the brain (20%), and the lung (20%). The response rate was highest in adrenal gland lesions (2/4; 50%), followed by lymph nodes (13/19; 68.4 percent) and liver (5/10; 50%), whereas rates were lowest for lesions in the lung (9/25; 36%), intraperitoneal metastases (1/4; 25%), and brain (1/5; 20%). Conclusions: In renal cell carcinoma, checkpoint inhibitors have a variable response at different metastatic sites, with the best response occurring in lymph nodes and the least occurring in soft tissue.

Cytomorphological Categorization of Thyroid Lesions according to The Bethesda System for Reporting Thyroid Cytology and Correlation with their Histological Outcome: An Indian Oncology Centre Experience.

Objective: The objective of this study was to report the experience of an Indian premiere tertiary care oncology center in reporting fine needle aspiration cytology of thyroid lesions according to the Bethesda system of reporting thyroid cytopathology (TBSRTC) given by National Cancer Institute (NCI). These were then correlated with their histopathological outcome, analyzing the level of specificity and sensitivity of the procedure. Material and Methods: Aspiration cytology of thyroid lesions, presented during a 5.5-year duration, was reported retrospectively and prospectively, according TBSRTC, and correlated with their histopathologic diagnosis. Results: A total of 431 patients were evaluated comprising 289 females and 142 males, with a median age of 52 years. Among the cytological categories 80 (18.6%) were non-diagnostic (ND), 131 (30.2%) benign, 45 (10.4%) follicular lesion of undetermined significance (FLUS), 27 (6.3%) follicular neoplasm, 33 (7.9%) suspicious for malignancy (SM), and 115 (26.7%) malignant. Histopathology reports were available in 142 of these cases. Final malignant diagnosis was reported in 11 of 14 ND (78.6%), 5 of 18 benign cases (27.7%); 9 of 17 FLUS (52.9%), 7 of 13 FLUS (53.89%), 19 of 20 SM (95%), and 58 of 60 malignant cases (96.7%). The procedure had sensitivity of 94.4%, specificity of 61.9%, positive predictive value of 90.3% and negative predictive value of 72.22%. Conclusion: TBSRTC provides uniform categorization of thyroid cytology, which also helps in further management. This valid system has helped to streamline the reporting terminologies as well as the clinical management.

Molecular stratification of high-grade urothelial carcinoma by immunohistochemistry with its histomorphological and clinical correlation.

Introduction: Urothelial carcinoma poses a significant cause of morbidity and mortality. The recent classification of Tumors of Urinary System by World Health Organization fourth edition) has elucidated its molecular subtypes and its associated prognostic significance. Methods: We used immunohistochemistry marker expression (CK5/6, CK20, CD44, EGFR) as a surrogate marker, to stratify 150 cases of high-grade urothelial carcinoma into the intrinsic molecular subtypes. A correlation was also done with immunohistochemical markers p53, p21, E-cadherin and Ki-67. Results: On subtyping, 47.3% cases were basal, 42.7% luminal and 10% remained unclassified. We did not find GATA3 useful for molecular stratification in our study. Muscle invasion was seen in 59% of basal and 31% of luminal subtype (P = 0.016). Squamous differentiation was most commonly associated with basal subtype (P < 0.001). EGFR expression was seen in 62% of basal and 38% of luminal subtype (P = 0.014), and thus can be used as an additional marker for molecular stratification. Overexpression of p53 was seen in 64% cases of muscle invasive and 36% of non-muscle invasive high-grade carcinomas (P < 0.0001). An inverse relationship was observed between p53 and p21 immunoexpression (r = -0.494) (P < .0001). The overall survival at 1- and 2-year interval was more in the luminal subtype, suggesting an early mortality in basal group, (P = 0.827), and at 6 years both the groups had almost similar results. Conclusion: High-grade urothelial carcinoma is challenging in terms of therapeutic strategy. Increased understanding of underlying molecular basis helps identifying targetable treatment options, and newer biomarkers will enhance predictive and prognostic stratification.