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.

Clinicopathological Characteristics and Prognostic Factors of Synchronous Endometrial and Ovarian Cancers-A Single-Institute Review of 43 Cases.

OBJECTIVES: The objectives of our study were to demonstrate the clinicopathological characteristics and determine the prognostic factors for women with synchronous primary cancers of the endometrium and ovary. METHODS: A retrospective analysis of 43 pathologically proven cases of synchronous primary endometrial and ovarian cancers diagnosed between January 2005 and December 2015 was carried out. Patients with uterine sarcomas, carcinosarcomas, borderline tumors, and nonepithelial tumors of the ovary and patients who received neoadjuvant chemotherapy were excluded from the study. Disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method. Multivariate analysis to determine independent prognostic factors was performed using the Cox regression model. RESULTS: Mean age at diagnosis was 48.49 years. The most common presenting symptom was abnormal uterine bleeding in 58.2% of the patients. Nineteen patients (44.2%) were obese, and 13 patients (30.2%) were overweight. Twelve patients (30%) were nulliparous, and 25 (58.2%) were premenopausal; 76.7% of the patients received adjuvant treatment after surgery. Mean follow-up period was 48.9 months. Twelve patients developed recurrence, and 7 patients died of recurrent disease. The 5-year DFS for all patients was 65.13%, and the 5-year OS was 79.75%. The 118-month DFS and 118-month OS were 65.13% and 72.50%, respectively. On multivariate analysis, grade 3 disease for both endometrial and ovarian cancers and presence of lymphovascular space invasion were associated with significantly worse 118-month DFS and OS, respectively. CONCLUSIONS: Women with synchronous primary endometrial and ovarian cancers are young, nulliparous, obese, and premenopausal and have a favorable overall prognosis. Grade 3 disease at both sites and presence of lymphovascular space invasion are independent prognostic factors for recurrence and survival, respectively.

Unmasking the Masquerade: Fine-Needle Aspiration Diagnosis of Dedifferentiated Liposarcoma Clinically Mimicking Lymphoma.

A preoperative diagnosis of dedifferentiated liposarcomas (DDLPS) on fine-needle aspiration cytology (FNAC) is rare with scarce indexed literature. Herein, we describe a case of DDLPS diagnosed on fine needle aspiration which was presumed to be a lymphoma clinically and radiologically.

Lymphoepithelial carcinoma of tongue - Devil in garbs of Hodgkin lymphoma: A case report and review of literature.

Lymphoepithelial carcinoma (LEC) of head and neck region predominantly arises in salivary gland, oral cavity, oropharynx, nasal cavity, paranasal sinuses, and larynx; those arising from tongue are rare. Morphologically, it is a poorly differentiated squamous cell carcinoma, with early regional and distant metastasis. Diagnosis of LEC can sometimes be challenging especially in small biopsy and more so when seen at unusual location. Combination of morphology and immunohistochemistry (IHC) helps the diagnosis. Herein, we report a rare third case of LEC arising from lateral border tongue, diagnosed in a 36-year-old male. The presented case highlights challenges faced during diagnosis in small biopsy. Treatment of LECs comprises of surgery followed by radiotherapy or combined chemoradiation. Though, almost 70% of LEC of oral cavity region present with cervical nodal metastasis, their prognosis remains favorable.

Primary Oropharyngeal SMARCA4-Deficient Carcinoma: Expanding the Diagnostic Spectrum in Head and Neck Cancer.

With the advent of molecular immunohistochemistry and next generation sequencing, Switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex altered tumors have gained recognition recently. SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily B member 1 (SMARCB1) and SMARCA4 are the primary SWI/SNF components altered in several recently described undifferentiated malignancies in head and neck region with predilection for paranasal sinuses in SMARCB1-deficient tumors and nasal cavity in SMARCA4-deficient tumors. However, to the best of our knowledge, SMARCA4-deficient tumors of the oropharynx have not been described. We present an unusual case of SMARCA4-deficient carcinoma of the oropharynx (palatine tonsil) which is the first case in the literature, expanding the topographic distribution of SMARCA4-deficient tumors in the head and neck region and emphasizing the importance of BRG1 as an essential immunohistochemical marker for the diagnosis of this distinct entity.

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.

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.

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.

Extraskeletal Myxoid Chondrosarcoma of Floor of Mouth-A Rare Case Report and Review of Literature.

Introduction: Chondrosarcomas are rare malignancies of the cartilage and myxoid chondrosarcoma is its variant which commonly occurs in soft tissue of extremities. Extraskeletal chondrosarcoma is a rare malignant neoplasm of bone or soft tissue origin and is characterized by the presence of spindle cells admixed with well differentiated cartilage or chondroid stroma. They are mostly radioresistant tumours and surgical resections with adequate margins is considered as the ideal treatment modality with adjuvant radiotherapy in high grade tumours and add on chemotherapy, in case of presence of poor prognostic factors. Case Report: A 51-year-old diabetic, hypertensive female patient presented to our outpatient department with difficulty in chewing food for a duration of 6 months. On clinical examination, she had an ulceroproliferative growth involving right lower alveolus and floor of mouth. MRI face and neck with contrast showed a 4.1 × 2.9 × 4.5 cm lesion involving right lower alveolus extending to floor of mouth. Biopsy showed features of extraskeletal myxoid chondrosarcoma. She was planned for upfront surgery (Right composite resection with modified radical neck dissection with free fibula flap). Patient was stable post-surgery and was discharged in stable condition. Final histopathology report was high grade myxoid chondrosarcoma. The case was presented in tumour board and the patient was planned for adjuvant radiotherapy. She has been on regular follow up for the past 2 years and shows no signs of recurrence. Conclusion: Extraskeletal myxoid chondrosarcoma of oral cavity is a rare entity and very few cases are reported. It is a malignant neoplasm which is diagnosed with the help of immunohistochemistry. Surgery is the ideal modality of treatment accompanied by adjuvant radiotherapy in cases of high-grade tumours.

AI-based pipeline for early screening of lung cancer: integrating radiology, clinical, and genomics data.

Background: The prognosis of lung carcinoma has changed since the discovery of molecular targets and their specific drugs. Somatic Epidermal Growth Factor Receptor (EGFR) mutations have been reported in lung carcinoma, and these mutant proteins act as substrates for targeted therapies. However, in a resource-constrained country like India, panel-based next-generation sequencing cannot be made available to the population at large. Additional challenges such as adequacy of tissue in case of lung core biopsies and locating suitable tumour tissues as a result of innate intratumoral heterogeneity indicate the necessity of an AI-based end-to-end pipeline capable of automatically detecting and learning more effective lung nodule features from CT images and predicting the probability of the EGFR-mutant. This will help the oncologists and patients in resource-limited settings to achieve near-optimal care and appropriate therapy. Methods: The EGFR gene sequencing and CT imaging data of 2277 patients with lung carcinoma were included from three cohorts in India and a White population cohort collected from TCIA. Another cohort LIDC-IDRI was used to train the AIPS-Nodule (AIPS-N) model for automatic detection and characterisation of lung nodules. We explored the value of combining the results of the AIPS-N with the clinical factors in the AIPS-Mutation (AIPS-M) model for predicting EGFR genotype, and it was evaluated by area under the curve (AUC). Findings: AIPS-N achieved an average AP50 of 70.19% in detecting the location of nodules within the lung region of interest during validation and predicted the score of five lung nodule properties. The AIPS-M machine learning (ML) and deep learning (DL) models achieved AUCs ranging from 0.587 to 0.910. Interpretation: The AIPS suggests that CT imaging combined with a fully automated lung-nodule analysis AI system can predict EGFR genotype and identify patients with an EGFR mutation in a cost-effective and non-invasive manner. Funding: This work was supported by a grant provided by Conquer Cancer Foundation of ASCO [2021IIG-5555960128] and Pfizer Products India Pvt. Ltd.

A Case Series of Neurolymphomatosis: Role of Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Scan Reiterated.

Neurolymphomatosis is rarely encountered in high-grade lymphomas. In this case series, we retrospectively analyzed six neurolymphomatosis cases to look for possible risk factors, common and uncommon presentations, and the lessons learned. Neuropathic pain was the most common symptom with mono or polyradiculopathy in this series. However, all lymphomatous infiltrated nerves diagnosed on fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) were not symptomatic. The lumbar, brachial plexus, and trigeminal nerve were the most common sites and were depicted well on FDG PET/CT. Magnetic resonance imaging (MRI) of the brain better delineates cranial nerves and meningeal involvement. Cerebrospinal fluid flow cytometry was normal until meninges were involved. FDG PET/CT incrementally evaluated extra-neural disease sites, thus helping in deciding biopsy sites and further management. We concluded that a whole-body FDG PET/CT including limbs with MRI brain was the appropriate investigation for evaluating suspected neurolymphomatosis in advanced-stage diffuse large B-cell lymphoma.

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.

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.

Macroscopic Extranodal Extension In Oral Squamous Cell Carcinoma-A Subgroup With Poor Survival.

BACKGROUND: Oral cancer portends a significant cause of morbidity and mortality worldwide. Cervical lymph node metastasis with extranodal extension (ENE) is associated with a poor prognosis. There has been accumulating evidence regarding the extent of ENE to be associated with prognosis and survival. AIM: This observational study was performed to analyze the prognostic implication of macroscopic and microscopic ENE in metastatic cervical lymph nodes of oral cavity cancer patients. METHODS: A total of 92 oral cavity cancer patients with pathologically detected ENE were included in this study. Both the groups (macroscopic and microscopic ENE) were compared in terms of overall survival and disease-free survival by using Kaplan -Meier. The pattern of failure was determined by Fischer's exact test. Univariate and multivariate analyses were calculated to determine the significant risk factors of death. RESULTS: The 2 years of disease-free survival and overall survival rates for the whole cohort were 51.2% and 53.9% respectively. The 2-year survival rate for the microscopic group (≤2 mm) and macroscopic (>2 mm) was 72.6% and 0% respectively, while the distal failure rate in microscopic ENE group and macroscopic ENE group was 22.22% and 44.83% respectively (p-value = 0.026). CONCLUSIONS: Macroscopic ENE (>2 mm) in oral cavity squamous cell cancer represents an aggressive entity with early regional and distant failure as compared to microscopic ENE (≤2 mm). Thus, macroscopic ENE (>2 mm) warrants a distinct subgroup with special consideration for intensification of treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:588-593, 2023.