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Abstract Background The mechanisms enabling dynamic shifts between drug-resistant and drug-sensitive states in cancer cells are still underexplored. This study investigated the role of targeted autophagic protein degradation in regulating ovarian cancer stem cell (CSC) fate decisions and chemo-resistance. Methods Autophagy levels were compared between CSC-enriched side population (SP) and non-SP cells (NSP) in multiple ovarian cancer cell lines using immunoblotting, immunofluorescence, and transmission electron microscopy. The impact of autophagy modulation on CSC markers and differentiation was assessed by flow cytometry, immunoblotting and qRT-PCR. In silico modeling and co-immunoprecipitation identified ID1 interacting proteins. Pharmacological and genetic approaches along with Annexin-PI assay, ChIP assay, western blotting, qRT-PCR and ICP-MS were used to evaluate effects on cisplatin sensitivity, apoptosis, SLC31A1 expression, promoter binding, and intracellular platinum accumulation in ID1 depleted backdrop. Patient-derived tumor spheroids were analyzed for autophagy and SLC31A1 levels. Results Ovarian CSCs exhibited increased basal autophagy compared to non-CSCs. Further autophagy stimulation by serum-starvation and chemical modes triggered proteolysis of the stemness regulator ID1, driving the differentiation of chemo-resistant CSCs into chemo-sensitive non-CSCs. In silico modeling predicted TCF12 as a potent ID1 interactor, which was validated by co-immunoprecipitation. ID1 depletion freed TCF12 to transactivate the cisplatin influx transporter SLC31A1, increasing intracellular cisplatin levels and cytotoxicity. Patient-derived tumor spheroids exhibited a functional association between autophagy, ID1, SLC31A1, and platinum sensitivity. Conclusions This study reveals a novel autophagy-ID1-TCF12-SLC31A1 axis where targeted autophagic degradation of ID1 enables rapid remodeling of CSCs to reverse chemo-resistance. Modulating this pathway could counter drug resistance in ovarian cancer.

Background: There can be a diagnostic challenge in differentiating giant cell tumor of bone (GCTB) from its mimics. Lately, histone H3F3A (Histone 3.3) G34W has been identified as a promising immunohistochemical marker. Aims: This study was aimed at evaluating H3.3 G34W immunostaining in 100 GCTBs, including its value in resolving diagnostic dilemmas. Materials and Methods: Immunohistochemical staining for H3.3 G34W was graded in terms of staining intensity (1+ to 3+) and the percentage of tumor cells showing crisp nuclear staining. Results: One hundred GCTBs occurred in 58 males and 42 females (M: F ratio = 1.3), of 7-66 years age (average = 31.3, median = 28), commonly in distal femur (26), followed by proximal tibia (17), distal radius (12), proximal humerus (7), metacarpals (7), sacrum (6), proximal fibula (6), and relatively unusual sites (19), including a single multicentric case. Out of 92 GCTBs, wherein H3.3 G34W immunostaining worked, 81 (88.1%) showed positive staining in the mononuclear cells, including tumors with fibrous histiocytoma-like areas, sparing osteoclast-like giant cells, with 3+ staining intensity in 65/81 (80%) tumors. All 7/7 (100%) malignant GCTBs showed positive staining, including the pleomorphic/sarcomatous cells. All 7/7 (100%) metastatic GCTBs showed positive immunostaining. Seven out of 10 post-denosumab treated GCTBs showed positive H3.3 G34W immunostaining in the residual mononuclear cells. None of the other 37 “giant cell-rich” lesions displayed H3.3 G34W immunostaining. Four of 9 GCTBs tested for H3.3 G34W mutation showed positive results. Conclusions: The diagnostic sensitivity and specificity of H3.3 G34W for GCTB were 88.1% and 100%, respectively. This constitutes one of the first reports from our country, further validating the diagnostic value of H3.3 G34W in differentiating GCTB, including metastatic and malignant forms from its mimics, including small biopsy samples. Its value in various diagnostic dilemmas is presented and utility in identifying residual tumor cells in post-denosumab treated GCTBs is worth exploring.

Clear cell adenocarcinoma (CCAC) of cervix is a rare subtype of endocervical adenocarcinoma that accounts for 4% of all cervical adenocarcinoma with many morphological mimickers. Retrospectively study cases of cervical clear cell adenocarcinoma of the cervix. Clinical profile and pathological features of CCAC of the cervix diagnosed between 2018-2022 were retrospectively analyzed.The database of the Department of Pathology of our institute was systematically searched for patients diagnosed with clear cell adenocarcinoma of the cervix during 2018-2022.A total of 19 patients were studied with the mean age of patients being 53.72 years (range 25 -84 yrs,standard deviation-25.9) and median tumor size being 5.6cm. Lymph node metastasis was identified in 33.3% and distant metastasis were seen in 20% of the cases. Staging could not be done in 4 cases.FIGO staging of the cases included IB1(2 cases), IB2(2 cases), IIB (3 cases),IIIA (1 case)IIIB(4 cases),and IV(3 cases). On histopathological evaluation, heterogeneous architectural pattern comprising of tubulocystic, solid, and papillary patterns were seen in 13 cases (13/19,68.4%). Pure tubulocystic (3/19,15.7%), pure papillary (2/19,10.5%), and pure solid patterns (1/19,5.3%) were also identified. Tumor cells with clear cytoplasm ranged from 5% to 95%. Nuclear atypia was moderate to marked in all the cases (19/19,100%). Mitotic activity varied from 1/10hpf to 20-22/10hpf. By immunohistochemistry, tumor was positive for Napsin A in all the cases,p16INK4a was negative in majority of cases (15/19,78.9%) and ER was negative in 14 cases (14/19,73.7%) .p53 showed wild type staining except for one case . Clear cell adenocarcinoma being a rare subtype of cervical adenocarcinoma, needs to be differentiated from other Human Papilloma Virus(HPV) independent adenocarcinomas (gastric and mesonephric types) and benign entities such as endocervical glandular Arias-Stella reaction. Judicious use of a panel of immunostains is often helpful.

Background: Infantile Ewing Sarcoma (ES) is an extremely rare disease with comparable outcomes on contemporary protocols. There is a paucity of data from India. Methods: Infants with proven ES diagnosed between January 2012 and December 2020 were retrospectively analyzed. The staging was performed using positron emission tomography-computerized tomography scan. Treated infants were administered weight-based chemotherapy. The local control was with surgery and/or radiotherapy. Results: There were 10 infants with ES with a male-to-female ratio of 2.3:1. The majority had extraosseous (90 %, n = 9) or axial primary (50 %, n = 5). Five patients with localized disease received treatment. Two died during induction chemotherapy (sepsis-1, cause unknown-1), and 3 are alive with no evidence of disease at a median follow-up of 8 years (range: 4–9). Two episodes of complicated febrile neutropenia were reported in 5 treated infants. Conclusions: ES in infants is rare and predominantly extraosseous with axial primary. Treated infants with non-metastatic disease tolerated chemotherapy well with good outcomes.

Malignant perivascular epithelioid tumors (PEComas) involving the uterus are uncommon. Herein, we present the clinicopathological features of two such cases, including their diagnostic implications with recent updates. A 62-year-old lady presented with vaginal bleeding. Ultrasonogram revealed a heterogeneous uterine mass. She underwent an endometrial biopsy and total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO), which revealed a 3.2 cm-sized proliferative tumor in the fundus. A 45-year-old lady presented with recurrent abdominal pain. She underwent cytoreductive surgery twice with adjuvant chemotherapy for multiple tumors and TAH-BSO for a uterine tumor, 2 years before. Microscopic examination of both tumors revealed markedly atypical, polygonal-shaped/epithelioid tumor cells containing eosinophilic cytoplasm and arranged in a nesting pattern with intervening thin-walled blood vessels, mitotic figures (≥ 6/10 high power fields (hpfs)), and tumor necrosis. Tumor infiltration was more than half the myometrial thickness in the first tumor and pelvic nodal metastasis. The second tumor revealed rhabdoid-like and vacuolated cells along with “spider-like” giant cells. Immunohistochemically, both the tumors were positive for HMB45 and desmin, while negative for epithelial markers. Additionally, the second tumor was positive for smooth muscle actin (SMA) and TFE3. Both patients developed tumor recurrences. In view of multiple tumor deposits, the second patient was induced with a mammalian target of rapamycin (m-TOR) inhibitor (everolimus) but unfortunately died of the disease. Malignant PEComas involving the uterus are ultra-rare, aggressive tumors. An index of suspicion, based on certain histomorphological features, supported by immunohistochemical expression of myomelanocytic markers is necessary for a correct diagnosis. Certain PEComas display TFE3 positivity. A correct diagnosis has significant implications, including an aggressive clinical course and the possibility of targeted therapy, especially in recurrences or metastasis.

Vulvo-vaginal stromal tumours are a rare and diverse group of mesenchymal neoplasms unique to hormone-responsive stroma of the vulva and vagina. These tumours are mostly benign, except for the locally aggressive deep angiomyxomas. Often these tumours pose diagnostic challenges, resembling certain malignant vulvo vaginal tumours.This case series highlights clinicopathological features of four angiomyxomas; a single angiomyofibroblastoma, and another superficial myofibroblastoma, including their clinical outcomes. All patients were in their 4th or 5th decade of life. Only 1/4 angiomyxomas was correctly diagnosed at the referring hospitals. Three out of four patients harbouring angiomyxomas achieved clinical remission post-surgery, while one patient was lost to follow-up. By immunohistochemistry, tumor cells showed variable positivity for desmin, SMA, ER, and PR, and negativity for S100P and CD34. The angiomyofibroblastoma was initially misdiagnosed as a liposarcoma, and the patient was lost to follow-up after diagnosis. Immunohistochemically, the tumor cells were diffusely positive for SMA and ER; weakly and focally positive for desmin, and negative for AE1/AE3, CD34, and S100P. The patient with superficial myofibroblastoma is in clinical remission post-excision with an 18-month follow-up. Immunohistochemically, the tumor cells showed CD34 positivity. Therapeutically, none of the patient received adjuvant treatment, except for a single patient with angiomyxoma, who underwent chemoradiation for a synchronous cancer cervix post-surgery.This case series provides valuable insights into the clinical heterogeneity, diagnostic intricacies, and outcomes of vulvo-vaginal stromal tumours from an oncology centre in India, further contributing to a better understanding of these rare tumours.

PURPOSEDesmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are associated with significant barriers including access, cost, and toxicities. This study aimed to explore the efficacy and safety of the metronomic therapy (MT) in DF in a large, homogenous cohort from India.PATIENTS AND METHODSThis study involved histologically confirmed DF cases treated with MT comprising vinblastine (6 mg) and methotrexate (15 mg) both once a week, and tamoxifen (40 mg/m2) in two divided doses once daily between 2002 and 2018.RESULTSThere were 315 patients with a median age of 27 years; the commonest site was extremity (142 of 315; 45.0%). There were 159 (50.1%) male patients. Of the 123 (39.0%) prior treated patients, 119 had surgery. Of 315 patients, 263 (83.5%) received treatment at our institute (MT—151, 77—local treatment, 9—tyrosine kinase inhibitor, and 26 were observed). Among the MT cohort (n = 163, 61.2%), at a median follow-up of 36 (0.5-186) months, the 3-year progression-free and overall survival were 81.1% (95% CI, 74.3 to 88.4) and 99.2% (95% CI, 97.6 to 100), respectively. There were 35% partial responses. Ninety-two patients (56.4%) completed 1-year therapy, which was an independent prognosticator (P < .0001; hazard ratio, 0.177 [95% CI, 0.083 to 0.377]). MT was well tolerated. Predominant grade ≥3 toxicities were febrile neutropenia, 12 (7.4%) without any chemotoxicity-related death. The annual cost of MT was $130 US dollars.CONCLUSIONThe novel, low-cost MT qualifies as one of the effective, less toxic, sustainable, standard-of-care options for the treatment of DF with global reach and merits wide recognition.

Inflammatory leiomyosarcoma (LMS) is a newly included rare tumor entity in the group of smooth muscle tumors in the recent WHO classification. Recent studies have shown skeletal muscle expression within this tumor and its proximity with histiocyte-rich rhabdomyoblastic tumor (HRRT). A 17-year-old male presented with a soft tissue lump over the back of his neck of one-year duration. Radiologically, a lesion measuring 5.9 cm in the largest dimension was seen, extending from the skull base up to the C2 vertebral level, abutting the occipital bone. The initial biopsy was reported as a fibrohistiocytic tumor at the referring laboratory. A microscopic review of the sections from the initial biopsy and subsequent resection revealed a well-circumscribed, cellular tumor composed of plump spindle and polygonal-shaped tumor cells with relatively bland nuclei, moderate to abundant eosinophilic cytoplasm and numerous interspersed histiocytes, including foam cells and lymphocytes. Immunohistochemically, the tumor cells were positive for desmin, MYOD1 and SMA, focally positive for myogenin, while negative for h-caldesmon, SOX10 and S100P. A diagnosis of inflammatory leiomyosarcoma/HRRT was offered. Subsequently, the tumor was tested for MYOD1 (L122R) mutation and was found to be negative. The patient underwent adjuvant radiation therapy and is free-of-disease at 12 months post-treatment. This case constitutes an extremely rare case of an inflammatory LMS/HRRT, identified in the neck region. This tumor should be differentiated from its close mimics, such as a spindle cell/sclerosing rhabdomyosarcoma, as the latter is treated more aggressively, including with chemotherapy, given its relatively poor prognosis.

Several defining molecular alterations have recently been identified underlying high-grade endometrial stromal sarcomas, such as YWHAE: NUTM2A/B fusions, ZC3H7B: BCOR fusions, and BCOR internal tandem duplication (ITD). BCOR is a useful immunohistochemical marker for identifying these tumors. A 37-year-old lady was presented with a 10-cm-sized tumor in the pouch of Douglas, involving the vaginal vault, bilateral adnexa, and peritoneum. A 53-year-old lady with a prior hysterectomy was presented with a 12-cm-sized tumor in the vault with abdominal deposits. Histopathological examination of both tumors revealed atypical cells comprising oval to spindle-shaped nuclei, a variable amount of myxoid stroma, and mitotic figures exceeding 10/10 high power fields. Immunohistochemically, the former tumor was diffusely positive for CD10, and the second tumor displayed patchy staining. Both tumors were positive for BCOR. Estrogen receptor (ER) showed variable staining in both tumors. By fluorescence in-situ hybridization (FISH), both tumors lacked YWHAE gene rearrangement. Both tumors had an aggressive clinical course, including extensive involvement This constitutes the first report of BCOR-positive high-grade sarcomas involving the female genital tract from our subcontinent. BCOR is a useful immunostain for identifying these relatively aggressive tumors. The differential diagnoses and the prognosis of these ultra-rare tumors are discussed herewith.

In the original publication [...]

Inflammatory myofibroblastic tumors (IMTs) are uncommon; intermediate grade soft tissue tumors occurring in young individuals with an uncertain behaviour. The incidence of pulmonary lymphangitis carcinomatosis (PLC) is around 6-8% of all pulmonary metastases. However, PLC due to papillary thyroid carcinoma (PTC) is very uncommon. We present a case of a 26-year-old male, who presented with a solitary left lung nodule on radiological scans. There was also a past history of thyroid surgery done two years back for PTC. Histology revealed a soft tissue tumor reminiscent of IMT. The periphery of the IMT nodule showed metastatic PTC in the form of extensive PLC. In view of this unusual histology, a diagnosis of PTC with nodular fasciitis-like stroma (PTC-NFS) was initially considered. However, molecular studies for anaplastic lymphoma kinase (ALK) gene rearrangement confirmed the diagnosis of IMT. This case highlights the unusual occurrence of tumor-to-tumor metastasis causing diagnostic challenges and also the importance of molecular testing.

Introduction: Loop electrosurgical procedure of the transformation zone of the cervix (LEEP) is the preferred method for many investigators for early detection and treatment of high grade intraepithelial neoplasia(HGCIN). Histopathology reports of LEEP should contain information about the diagnosis, presence or absence of neoplasia ( with its grade) and comment on excison margins. Aim: Our aim was to study LEEP reports for its contents and to see their correlation with preprocudure histology and/or cytology report. Results: Between 2011 and 2017, 44 LEEP reports were archived and studied for their contents from our records. Slides were not reviewed. Mean age was 47.66 years (median 47 years). Forty two (( 95.45%) reports mentioned that all the tissue was examined. Deep cut examination was mentioned in 17/44 cases (38.64%). The concordance rate between LEEP and preprocudure histology and /or cytology for CIN II plus diagnosis is 65.9%. A strict definition is used. If, however, diagnoses between inflammation and CIN I, ASC-H and inflammation, and ASC-H and CIN I are considered non discordant, then the concordance rate rises to 72.7 %. The breakup of discordant cases is given. Conclusion: Literature shows wide range of concordance due to variable definitions and variety of reasons; possible reasons are discussed.

This case report aims to present clinicopathological features of an extremely rare case of multifocal pseudomyogenic hemangioendothelioma (PMHE) in the scalp. A 21-year-old male developed multiple, focally ulcerated, nodules over the root of his nose and scalp. One of the skin lesions was sampled at another dermatology clinic, where this was diagnosed as a sarcoma. A review of biopsy sections showed well-circumscribed dermal lesions, comprising plump spindle and epithelioid cells, mimicking rhabdomyoblasts. Immunohistochemically, tumor cells were positive for AE1/AE3, CD31, FLI-1 and ERG. INI-1 was retained. A diagnosis of PMHE was offered. Subsequently, the patient underwent wide excision and has been asymptomatic for 8 months, post-surgery. PMHE is rarely reported in the head and neck region, where it can constitute a diagnostic pitfall. Awareness of this tumor and appropriate immunohistochemical stains are necessary for its timely diagnosis, in order to avoid radical treatments. A review of similar, previously documented cases is presented.

Background: Liposarcomas including atypical lipomatous tumors (ALT)/well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPSs) display a histomorphological spectrum with their several diagnostic mimics. Murine double minute 2(MDM2) gene amplification characterizes ALT/WDLPS and DDLPS. Presently, there is no documented study from our subcontinent on the validation of MDM2 gene testing in these tumors. Material and Methods: Twenty-eight cases, diagnosed as ALT/WDLPS (n = 5) and DDLPSs (n = 23), along with 10 other tumors were tested for MDM2 gene amplification, using fluorescence in situ hybridization (FISH) on tissue microarrays (TMAs). Fourteen cases, diagnosed as ALT/WDLPS and DDLPS, along with 49 other tumors were tested for MDM2 immunostaining. Twenty tumors were tested for p16INK4a immunostaining. Results: FISH was interpretable in 25 (89.2%) cases. Among the 20 cases diagnosed as DDLPSs, 19 displayed MDM2 gene amplification. Among the 5 cases diagnosed as ALT/WDLPS, four showed MDM2 gene amplification. Finally, 19 cases were confirmed as DDLPS and 4 as ALT/WDLPS. Furthermore, 7/19 cases confirmed as DDLPS and all 4 cases as ALT/WDLPS tested for MDM2 immunostaining, displayed its diffuse immunoexpression, while a single case of DDLPS showed its focal immunostaining. None of the 49 control cases displayed diffuse MDM2 immunoexpression. ALL 16 DDLPSs and 4 cases of ALT/WDLPS displayed p16INK4a immunostaining. The sensitivity for diffuse MDM2 immunostaining was 87.5% in cases of DDLPS, 100% in ALT/WDLPS, and specificity was 100%. The sensitivity for MDM2 gene amplification was 94.7% in cases of DDLPS and 100% in cases of ALT/WDLPS. The sensitivity for p16INK4a was 100%. Conclusion: This constitutes the first sizable study on MDM2 testing in ALT/WDLPS and DDLPS from our subcontinent using TMAs. MDM2 gene amplification testing continues as the diagnostic gold standard for ALTs/WDLPSs and DDLPSs and is useful in cases of diagnostic dilemmas. Diffuse MDM2 (IF2 clone) and p16INK4a immunostaining, together seem useful for triaging cases for FISH.

Objectives Peritoneal tuberculosis can mimic advanced abdominal malignancy. We describe clinical and laboratory characteristics in a series of female patients with peritoneal tuberculosis who were referred to a tertiary cancer center with a diagnosis of suspected advanced ovarian/primary peritoneal cancer. Materials and Methods Details of clinical features, laboratory results including serum tumor markers, radiological findings, and ascitic fluid evaluation were retrospectively collected from hospital records for patients diagnosed to have peritoneal tuberculosis and reported descriptively. Statistical Analysis Descriptive statistics was performed using SPSS Statistics for Windows software, version 20.0 (SPSS, Chicago, Illinois). Results Between January 2009 and December 2017, 120 patients of peritoneal tuberculosis with a median age 41 years (range, 15–79 years) were identified. Of these 112 (93.3%; 95% CI 88.9–97.8%) patients had ascites and 63 (52.5%; 95% CI 43.6–61.4%) had adnexal mass at presentation. Mean serum cancer antigen 125 (CA-125) level was 666.9 (range, 38–18,554) U/mL. Ascitic fluid was negative for malignant cells in all patients and lymphocyte rich exudate was seen in 103 (91.9%; 86.9–97.0%) patients. Ascitic fluid adenosine deaminase (ADA) level was more than 40 U/L in 107 (95.5%; 95% CI 91.7–99.4%). Ascitic fluid Ziel–Neelsen staining was positive in 4/62 (6.5%; 95% CI 0.3–12.6%) patients while ascitic fluid culture examination for mycobacterium tuberculosis was positive in 7/59 (11.9%; 95% CI 3.6–20.1%) patients. The diagnosis of tuberculosis was based on image-guided biopsy in 44 (36.7%) patients, surgical biopsy in 8 (6.7%) patients, and a combination of clinicoradiological and laboratory features in 68 (56.7%) patients. All patients received standard antitubercular treatment. Conclusions The study results suggest that peritoneal tuberculosis has clinical, radiological, and serological profile which may mimic advanced ovarian/primary peritoneal cancer. Peritoneal tuberculosis should be considered in the differential diagnosis of advanced abdominal malignancy.

Abstract Alterations in key kinases and signaling pathways can fine-tune autophagic flux to promote the development of chemoresistance. Despite empirical evidences of strong association between enhanced autophagic flux with acquired chemoresistance, it is still not understood whether an ongoing autophagic flux is required for both initiation, as well as maintenance of chemoresistance, or is sufficient for one of the either steps. Utilizing indigenously developed cisplatin–paclitaxel-resistant models of ovarian cancer cells, we report an intriguing oscillation in chemotherapy-induced autophagic flux across stages of resistance, which was found to be specifically elevated at the early stages or onset of chemoresistance. Conversely, the sensitive cells and cells at late stages of resistance showed stalled and reduced autophagic flux. This increased flux at early stages of resistance was found to be dictated by a hyperactive ERK1/2 signaling, which when inhibited either pharmacologically (U0126/Trametinib) or genetically, reduced p62 degradation, number of LC3+veLAMP1+ve puncta, autophagolysosome formation, and led to chemo-sensitization and apoptosis. Inhibition of ERK1/2 activation also altered the level of UVRAG and Rab7, the two key proteins involved in autophagosome–lysosome fusion. Noninvasive imaging of autophagic flux using a novel autophagy sensor (mtFL-p62 fusion reporter) showed that combinatorial treatment of platinum–taxol along with Trametinib/chloroquine blocked autophagic flux in live cells and tumor xenografts. Interestingly, Trametinib was found to be equally effective in blocking autophagic flux as chloroquine both in live cells and tumor xenografts. Combinatorial treatment of Trametinib and platinum–taxol significantly reduced tumor growth. This is probably the first report of real-time monitoring of chemotherapy-induced autophagy kinetics through noninvasive bioluminescence imaging in preclinical mouse model. Altogether our data suggest that an activated ERK1/2 supports proper completion of autophagic flux at the onset of chemoresistance to endure initial chemotherapeutic insult and foster the development of a highly chemoresistant phenotype, where autophagy becomes dispensable.

Epithelial ovarian cancer (EOC) is the deadliest gynaecological malignancy and the eighth most prevalent cancer in women, with an abysmal mortality rate of two million worldwide. The existence of multiple overlapping symptoms with other gastrointestinal, genitourinary, and gynaecological maladies often leads to late-stage diagnosis and extensive extra-ovarian metastasis. Due to the absence of any clear early-stage symptoms, current tools only aid in the diagnosis of advanced-stage patients, wherein the 5-year survival plummets further to less than 30%. Therefore, there is a dire need for the identification of novel approaches that not only allow early diagnosis of the disease but also have a greater prognostic value. Toward this, biomarkers provide a gamut of powerful and dynamic tools to allow the identification of a spectrum of different malignancies. Both serum cancer antigen 125 (CA-125) and human epididymis 4 (HE4) are currently being used in clinics not only for EOC but also peritoneal and GI tract cancers. Screening of multiple biomarkers is gradually emerging as a beneficial strategy for early-stage diagnosis, proving instrumental in administration of first-line chemotherapy. These novel biomarkers seem to exhibit an enhanced potential as a diagnostic tool. This review summarizes existing knowledge of the ever-growing field of biomarker identification along with potential future ones, especially for ovarian cancer.

PURPOSEThere are limited data on management of cervical cancer in women living with HIV in the modern antiretroviral therapy era. The study aimed to evaluate outcomes and toxicities of these patients treated with radiotherapy.MATERIALS AND METHODSA retrospective analysis of HIV-positive cervical cancer patients treated with radiotherapy between 2011 and 2018 was conducted at a tertiary care center in India.RESULTSEighty-two HIV-positive cervical cancer patients treated with radiotherapy were identified. Their median age was 45 years. Seventy-four (90%) patients received radiotherapy with curative-intent and eight patients received palliative radiotherapy. Median CD4 count at the start of treatment was 342 cells/mm3 (interquartile range: 241-531). Among patients planned for definitive radiotherapy, concurrent cisplatin was planned in 52 (70%) patients with a median of four chemotherapy cycles, and 81% (n = 60) patients received brachytherapy. Among patients who received brachytherapy, the median prescription dose was 80 Gy. Seventy-seven patients completed their prescribed treatment. At a median follow-up of 37 months, 3-year disease-free survival of patients planned with curative-intent was 54%. On multivariate analysis, treatment completion was associated with favorable disease-free survival. Grade III/IV acute gastrointestinal toxicity was seen in five (6.8%) patients, whereas 30% patients had grade III/IV acute hematologic toxicity. All these patients completed their planned radiotherapy with good supportive care.CONCLUSIONStandard treatment of chemoradiation should be planned in women living with HIV with well-managed HIV presenting with locally advanced cervical cancer. Our study highlights the need for optimal management of these patients by a multidisciplinary team with intensive supportive care to ensure completion of planned treatment to achieve better outcomes.

Epithelioid sarcoma (ES) is rare and aggressive soft tissue neoplasm characterized by tumor cells showing epithelioid morphology and immunohistochemically, characteristic loss of INI1/ SMARCB1 in most cases. The proximal-type ES usually involves the deeper soft tissues of the vulva or perineum is an extremely rare entity with diagnostic challenges. Surgery is the mainstay of treatment in localized diseases. Radiation and chemotherapy are used in the advanced and metastatic setting, however, their role in the adjuvant setting is uncertain. Anthracycline and gemcitabine-based chemotherapy are given in metastatic and recurrent tumors. We report 4 cases of ES treated over a period of 6 years at our center. All the cases initially presented at a local hospital with vulvar swelling with a benign mimic (3/4) or squamous cell carcinoma (1/4). The median age of diagnosis was 34 years (range 17–80). The diagnosis was established with epithelioid morphology of tumor cells and immunohistochemically characteristic loss of INI1/SMARCB1 in all cases. 3 cases were treated with upfront surgery and two of them received adjuvant radiotherapy. One case received upfront palliative therapy due to lung metastasis at the time of presentation. On median follow-up of 24 months (2–63), 2 cases were disease-free. One case had a recurrence in the lungs and chest wall after a disease-free interval of 63 months. She underwent surgical excision of metastatic deposits, however developed second lung recurrence after 3 months and is being treated with Adriamycin-based chemotherapy. All patients are alive at the last follow-up.

Patient-specific precision medicine approaches are important for future cancer therapies. Here, the authors show that functional drug profiling with Rhabdomyosarcoma cells isolated from PDX and primary patient tumors uncovers patient-specific vulnerabilities.

Dedifferentiated liposarcoma (DDLS) is characterized by a wide histopathological spectrum. Spindle cell type of rhabdomyoblastic dedifferentiation has been rarely described in case of DDLS. A 39-year-old male presented with a recurrent retroperitoneal tumor mass, diagnosed as well-differentiated liposarcoma, for which he underwent surgical excisions on two occasions, followed by adjuvant radiation therapy previously. Computed tomogram scan his of abdomen revealed a large-sized, fat-containing recurrent, retroperitoneal mass, measuring 18.1 cm in the largest dimension. Histopathologic examination of the resected tumor revealed distinct areas of well- and dedifferentiated liposarcoma, including areas reminiscent of a myxofibrosarcoma, further progressing into a high-grade spindle cell sarcoma with fascicular and “Herringbone-like” growth patterns (fibrosarcoma-like). Immunohistochemically, high-grade spindle cell sarcomatous (dedifferentiated) component displayed distinct positivity for desmin and MyoD1, along with focal tumor nuclei, showing nuclear positivity for myogenin. Both well-differentiated liposarcomatous and dedifferentiated components displayed diffuse, intense nuclear positivity for MDM2 (overexpression) and p16INK4A. Furthermore, upon testing tumor sections displaying spindly sarcomatous areas for MDM2 amplification, by FISH technique, nearly all tumor cells displayed MDM2 gene amplification. This case constitutes one of the rare cases of DDLS displaying spindle cell rhabdomyoblastic dedifferentiation. Its diagnostic and treatment implications are discussed herewith.

Cytological examination plays an important role in the initial work-up of the serous cavity effusion fluids to find out the possible etiology as benign or malignant. Among malignant effusions, cytology is helpful in determining the exact type, site, and stage of the tumor. However, for reporting effusion cytology specimens, there is no consistent and reproducible reporting system. Aims: The aim of these guidelines is to provide a standardized format for effusion cytopathology right from sample receipt to its ultimate report sign-out for implementation in all cytopathology laboratories. The Indian Academy of Cytologists in consultation with experts across the country has prepared guidelines pertaining to collection, preparation, and diagnostic categories of effusion specimens to reduce reporting variability. The guidelines are made keeping in mind the different areas of practices in India, especially low- and medium-resource settings. The guidelines are broadly divided into essential, optimal, and optional categories for best usage and appropriate allocation of the precious specimens. In referral centers or well-established setups, essential ancillary techniques can be done for accurate and final diagnosis. By adhering to and implementing these uniform guidelines, it is hoped that clinical patient care and management in India will improve and be of uniformly good quality by enabling and facilitating good laboratory practices.

One of the common indications of ascitic fluid examination in gynecological oncopathology is the detection and classification of malignant cells, especially in cases of clinically suspicious tubo-ovarian masses. The present study was undertaken to assess and validate the diagnostic utility of cell blocks (CBs) and compare its results with the corresponding conventional smears, prepared from effusion samples. CBs were prepared by thromboplastin technique in 220 cases. In 208 cases, diagnostic concordance between results obtained from smears and corresponding CBs was evaluated. Various antibody markers were tested, as per individual case. The average age of patients was 52.2 years. Positive immunohistochemical (IHC) staining for various markers was observed in 182 cases (82.7%) The most frequently positive antibody marker was PAX8 (101/134), followed by p53 (85/92) [mutation type (either diffusely positive or completely negative)], WT1 (tumor cells) (80/112), calretinin (2/87) (diffuse), BerEP4 (21/49), CA125 (21/24), CK7 (31/39) and CK20 and CDX2, together (5/16). Various other IHC markers utilized, including their positive expression, were TTF1 (1/10), p40 (3/3), p63 (2/4), ER (21/29), HBME1 (1/7), GATA3 (1/4), and MIC2 (1/1). Complete diagnostic concordance between CBs and smears was observed in 170/208 cases (81.7%). There were 20 major discordances, 10 minor and 8 cases with sampling errors. IHC was useful in classifying 158/182 (86.8%) cases, including serous or Müllerian adenocarcinoma (n = 123), mostly high-grade (121); metastatic squamous carcinoma (3); gastrointestinal-type adenocarcinoma (8); pulmonary adenocarcinoma (1); breast adenocarcinoma (1); Ewing sarcoma (1); and mesothelioma (2). CBs are complementary to smears in the detection of gynecological malignancies, mostly high-grade serous adenocarcinomas. These provide an opportunity for testing several IHC markers, for a precise diagnosis, including in various uncommon case scenarios, associated with significant therapeutic implications.

In spite of the advent of many high throughput technologies, tumor tissue biomarkers are still the gold standard for diagnosis and prognosis of different malignancies including epithelial ovarian cancer (EOC). EOC is a heterogeneous disease comprised of five major subtypes which show distinct clinicopathological features and therapy response. Acquirement of chemoresistance toward therapy is a major challenge for successful treatment outcome in EOC patients. Several markers have been tested by immunohistochemical method to evaluate their prognostic merit to predict clinical outcome. However, a vast majority of such markers have been assessed for high-grade serous and clear cell ovarian cancer, among all subtypes of EOC. The current review elaborates upon those biomarkers that can potentially predict chemoresistance with subtype specificity.

Over the years, immunohistochemistry has emerged as a powerful tool for a more precise diagnosis of certain tumors in gynecologic oncopathology and resolving certain diagnostic dilemmas with significant treatment implications. Certain specific immunohistochemical (IHC) markers have been useful in the more correct identification of rare tumors, characterized by specific molecular signatures. Immunohistochemistry has also been useful in the identification of underlying genetic events, characterizing various tumors, as well as precancerous lesions. This review will focus upon the judicious application of various IHC antibody markers in gynec oncopathology, including authors' experience during “sign-outs” and especially during interaction with other oncology colleagues within the institutional disease management group. The updated references were retrieved from PubMed.

COVID-19, caused by the SARS-CoV-2 virus, has been declared a pandemic by the World Health Organization. This scenario has impacted the way we practice cytopathology. Cytology laboratories receive fresh and potentially infectious biological samples including those from the respiratory tract, from COVID-19 positive or suspected patients. Hence, the Indian Academy of Cytologists thought it necessary and fit to bring forth appropriate guidelines starting from transportation, receipt, processing, and reporting of samples in the COVID-19 era. The guidelines are prepared with the aim of safeguarding and protecting the health care personnel including laboratory staff, trainees and cytopathologists by minimizing exposure to COVID-19 so that they remain safe, in order to able to provide a continuous service. We hope that these national guidelines will be implemented across all cytopathology laboratories effectively.

A solitary fibrous tumor (SFT), although ubiquitous, is rarely documented in the female genital tract, especially confirmed by STAT6 immunostaining and underlying NAB2-STAT6 gene fusion. A 24-year-old female presented with a gradually increasing vulvar swelling in her right labia, which rapidly increased in size over 1-year duration. Radiologically, a subcutaneous, predominantly solid, lobulated mass, measuring 10 cm in the largest dimension was seen involving her right labia majora and perineum. She underwent tumor resection, elsewhere, where it was reported as a pleomorphic sarcoma. Histopathologic review revealed a cellular tumor comprising spindle cells, displaying mild nuclear variation, arranged diffusely and focally, in a hemangiopericytomatous growth pattern, within a collagenous stroma. Interspersed were blood vessels with perivascular hyalinization and few giant cells. By immunohistochemistry, tumor cells showed patchy immunostaining for CD34 and diffuse immunostaining for STAT6. Furthermore, the tumor displayed NAB2ex6-STAT6ex 17 fusion by RT-PCR technique. This case constitutes one of the few reported cases of vulvar SFT, confirmed by STAT6 immunostaining and the second such case, displaying NAB2-STAT6 gene fusion. Diagnostic and treatment implications are discussed herewith.

BackgroundTreatment of malignant melanoma has undergone a paradigm shift with the advent of immune checkpoint inhibitors (ICI) and targeted therapies. However, access to ICI is limited in low-middle income countries (LMICs).Patients and MethodsHistologically confirmed malignant melanoma cases registered from 2013 to 2019 were analysed for pattern of care, safety, and efficacy of systemic therapies (ST).ResultsThere were 659 patients with a median age of 53 (range 44–63) years; 58.9% were males; 55.2% were mucosal melanomas. Most common primary sites were extremities (36.6%) and anorectum (31.4%). Nearly 10.8% of the metastatic cohort were BRAF mutated. Among 368 non-metastatic patients (172 prior treated, 185 de novo, and 11 unresectable), with a median follow-up of 26 months (0–83 months), median EFS and OS were 29.5 (95% CI: 22–40) and 33.3 (95% CI: 29.5–41.2) months, respectively. In the metastatic cohort, with a median follow up of 24 (0–85) months, the median EFS for BSC was 3.1 (95% CI 1.9–4.8) months versus 3.98 (95% CI 3.2–4.7) months with any ST (HR: 0.69, 95% CI: 0.52–0.92; P = 0.011). The median OS was 3.9 (95% CI 3.3–6.4) months for BSC alone versus 12.0 (95% CI 10.5–15.1) months in any ST (HR: 0.38, 95% CI: 0.28–0.50; P < 0.001). The disease control rate was 51.55%. Commonest grade 3–4 toxicity was anemia with chemotherapy (9.5%) and ICI (8.8%). In multivariate analysis, any ST received had a better prognostic impact in the metastatic cohort.ConclusionsLarge real-world data reflects the treatment patterns adopted in LMIC for melanomas and poor access to expensive, standard of care therapies. Other systemic therapies provide meaningful clinical benefit and are worth exploring especially when the standard therapies are challenging to administer.

An active fluidic microenvironment governs peritoneal metastasis in epithelial ovarian cancer (EOC), but its critical functional/molecular cues are not fully understood. Utilizing co-culture models of NIH3T3 cells (differentially overexpressing Jagged1) and SKOV3 cells expressing a Notch3 luciferase reporter-sensor (SNFT), we showed that incremental expression of Jagged1 led to proportional Notch3 activation in SNFT. With no basal luciferase activity, this system efficiently recorded dose-dependent Notch3 activation by rh-Jag1 peptide and the non-appearance of such induction in co-culture with NIH3T3Δjag1 cells indicates its sensitivity and specificity. Similar Notch3 modulation was shown for the first time in co-cultures with HGSOC patients’ ascites-derived cancer-associated fibroblasts and Jagged1-expressing EOC cell lines. NIH3T3J1-A and OVCAR3 co-cultured SNFT cells showed maximum proliferation, invasion, and cisplatin resistance among all the heterotypic/homotypic cellular partners. VEGFA and CDKN1A are the two most upregulated genes identified across co-cultures by the gene profiler array. Co-culture induced VEGFA secretion from SNFT cells which also reduced cancer stem cell differentiation in platinum-resistant A2780 cells. rh-Jag1-peptide promoted enhanced nuclear-cytoplasmic p21 expression. Additionally, metastatic HGSOC tumors had higher VEGFA than corresponding primary tumors. This study thus demonstrates the tumoral and non-tumoral cell-mediated differential Notch3 activation imparting its tumorigenic effects through two critical molecular regulators, VEGFA and p21, during EOC progression.

Bacground: Primary bone sarcomas mainly metastasize through haematogenous route and rarely through lymph nodes due to paucity of lymphatic channels in the bone (1). Nodal spread in chondrosarcoma is extremely rare and there are two reported cases in literature including one previously published by our institute (3, 5). Aims and Objectives: We present a series of chondrosarcoma cases (primary tumour located in the scapula, proximal femur, proximal humerus and pelvis), presenting with lymph node metastasis, treated at our institute. We assessed the oncological outcome of these cases and the impact of nodal metastasis on survival. Materials and Methods: Between January 2006 and December 2015, 243 patients of extremity and pelvic chondrosarcoma were operated at our institute. These cases were retrieved from a prospectively maintained database. Four (1.6%) of these patients developed lymph node metastasis. Clinical and radiological details of these cases were retrieved from electronic medical records and case files. Histopathology of the primary chondrosarcoma lesion and nodal metastasis was reconfirmed by a pathologist specializing in sarcomas. Conclusion: Lymph node metastasis though extremely rare in primary osseous chondrosarcoma, definitely affects their survival adversely. The rarity of the occurrence of lymph node metastasis in primary osseous tumors, especially chondrosarcoma highlights the need for multi institutional studies to pool knowledge and evaluate the prognostic significance and etiopathogenesis of lymph node metastasis in primary bone chondrosarcoma.

Fine needle aspiration cytology (FNAC) for diagnosis of musculoskeletal tumors is well discussed and debated. The current evidence restricts its application in recurrent and metastatic lesions, with core needle biopsy as the acceptable technique/gold standard for the primary diagnosis of these challenging tumors. However, there are several studies showing reasonable sensitivity and specificity in primary diagnosis of bone and soft tissue tumors, especially in differentiating benign from malignant tumors. There is an acceptable limitation in the exact subtyping of soft tissue tumors, based on cytology smear examination, in the absence of ancillary techniques. Nonetheless, cytology constitutes an optimal material for triaging cases for ancillary techniques, such as immunocytochemistry, immunohistochemistry, molecular cytogenetics, and molecular diagnosis, in the form of smears and cell block preparations. This review focuses on the strengths and limitations of cytology versus core needle biopsy in the diagnosis of bone and soft tissue tumors, with the current evidence in the form of published studies, including the authors' experience.

Small round cell lesions of the bone encompass a heterogeneous group of tumors and tumor-like lesions, including Ewing sarcoma, small cell osteosarcoma, mesenchymal chondrosarcoma, neuroblastoma, non-Hodgkin's lymphoma (NHL), “Ewing-like” undifferentiated round cell sarcomas, metastasizing small cell carcinoma, along with plasma cell dyscrasia and Langerhan's cell histiocytosis. At the same time, there are tumor mimics, for example, chronic osteomyelitis, which has overlapping radiologic features with Ewing sarcoma and a primary intraosseous NHL. An exact diagnosis necessitates integration of clinical, radiologic, pathologic, and ancillary test results, including immunohistochemical and molecular results. Currently, there are several immunohistochemical markers and specific molecular signatures, driving most of these tumors, available, for an exact diagnosis. This review focuses on a pragmatic approach towards uncovering specific small round cell lesions of the bone, emphasizing upon integration of traditional morphology with ancillary techniques, including immunohistochemical markers and molecular techniques, the latter, especially in cases of Ewing sarcoma, Ewing-like undifferentiated round cell sarcoma, mesenchymal chondrosarcoma, and neuroblastoma. Subsequent to the diagnostic approach, including an impact on treatment, individual intraosseous round cell lesions have been described in detail. The references include updated articles from PUBMED.

Standard guidelines for the management of early and locally advanced cervical cancer are available from various academic consortiums nationally and internationally. However, implementing standard-of-care treatment poses unique challenges within low- and middle-income countries, such as India, where diverse clinical care practices may exist. The National Cancer Grid, a consortium of 108 institutions in India, aims to homogenize care for patients with cervical cancer by achieving consensus on not only imaging and management, but also in addressing potential solutions to prevalent challenges that affect the homogenous implementation of standard-of-care treatment. These guidelines therefore represent a consensus statement of the National Cancer Grid gynecologic cancer expert group and will assist in homogenization of the therapeutic management of patients with cervical cancer in India.

Purpose: Metastatic osteosarcoma is largely treated with high-dose methotrexate (HDMTX)–based therapy, especially in the pediatric population. This mandates complex pharmacokinetic monitoring in a costly inpatient setting to mitigate unpredictable serious toxicities. Hence, a non-HDMTX–based regimen is worth exploring, especially in India and low- and middle-income countries. Materials and Methods: All consecutive treatment-naïve patients with metastatic osteosarcoma were prospectively treated on the novel OGS-12 protocol consisting of sequential doublets of doxorubicin, cisplatin, and ifosfamide. Four cycles were administered as neoadjuvant therapy followed by planned curative intent surgery and metastasectomy when feasible, followed by four cycles of adjuvant chemotherapy. Baseline characteristics, histologic response, event-free survival (EFS), overall survival (OS), and toxicity data were prospectively collected. Results: Three hundred seventeen patients were enrolled onto the OGS-12 protocol from 2011 to 2014, of whom 80 (25%) had metastatic disease; median age was 17 years. The majority of patients were nutritionally challenged with high-risk features. At presentation, 83% of patients (66 patients) had lung metastases. After neoadjuvant chemotherapy, 57% of patients were histologically good responders. Four-year EFS and OS rates were 24% and 27%, respectively, in the intent-to-treat population and 27% and 29%, respectively, in the per-protocol analysis. Significant grade 3 or 4 toxicities were febrile neutropenia (51%), thrombocytopenia (36%), and anemia (54%). Histologic response was an independent predictor for EFS and OS in patients who underwent surgery. Surgical intervention was found to be significant for survival in univariable analysis. Conclusion: The novel, low-cost, non-HDMTX–based, dose-dense OGS-12 regimen has shown comparable outcomes to international standards in metastatic osteosarcomas and is worthy of wider clinical application. An aggressive multimodality approach may result in long-term survival in a select group of patients and, hence, is worth considering.

A 28-year-old lady presented with multiple swellings in her left shoulder, associated with intermittent pain since last one and a half years. Radiologic imaging revealed multiple, well-defined, subcutaneous lesions in her left supraclavicular region. Fine needle aspiration cytology (FNAC) smears were initially reported as Ewing sarcoma, elsewhere. On review, the smears showed cohesive clusters of round-to-oval cells with scant cytoplasm, which were focally arranged in an acinar-rosetting pattern around hyaline "droplets/bodies," along with few scattered lymphocytes against a background of red blood cells. The diagnosis considered was adnexal tumor. Subsequent biopsy from the multiple lesions confirmed the diagnosis of eccrine spiradenoma. By immunohistochemistry, tumor cells were positive for CK7, epithelial membrane antigen (focally), S100 protein, and tyrosine-protein kinase Kit(C-KIT) /Cluster of differentiation (CD117). This case underscores the value of FNAC in skin adnexal tumors and constitutes as the first case report of multiple eccrine spiradenomas, initially misdiagnosed as Ewing sarcoma. Literature review of similar reported cases with treatment implications are presented.

Background: A wide clinicopathologic spectrum of a chordoma exists. Brachyury constitutes as its most useful diagnostic immunohistochemical (IHC) marker. Methods: During a 7-year-period, 4 unusual histopathologic types of chordomas were identified. Immunohistochemistry was performed by polymer technique. Results: Clinicopathologic features of the 4 cases are as follows: Cases 1 and 2: Two tumors occurred in the sacrococcygeal and lumbosacral regions of a 42-year-old male and a 34-year-old female, respectively. Histopathologic examination showed areas of classical chordoma; juxtaposed to a high-grade, spindle cell sarcoma. By IHC, cytokeratin (CK), epithelial membrane antigen (EMA), S-100 protein, and brachyury were found to be distinctly positive in the differentiated chordomatous areas. Both these cases were diagnosed as dedifferentiated chordomas. The first patient, postresection and adjuvant radiation therapy (RT), died after 14 months of therapy. Case 3: A 58-year-old male presented with pain in his sacral region and urinary incontinence. Imaging disclosed a sacral mass. Histopathologic examination showed physaliphorous cells intimately admixed with, markedly pleomorphic cells, scattered mitotic figures, and focal tumor necrosis. By IHC, the tumor cells were positive for CK, AE1/AE3, S-100 protein, brachyury, and INI1/SMARCB1. The diagnosis of a poorly differentiated chordoma was offered. Despite surgical resection and adjuvant RT, the patient died within 18 months. Case 4: A 58-year-old male presented with a soft tissue lesion in his left leg. Histopathologic examination showed physaliphorous cells, embedded in a myxohyaline stroma. By IHC, the tumor cells were positive for EMA, S-100 protein, brachyury, and INI1. Diagnosis of an extra-axial, soft tissue chordoma was offered. Conclusions: These four unusual chordomas, confirmed by brachyury immunoexpression, constitute as one of the first such documentation from our country, revealing a wide clinicopathologic spectrum of chordomas. Dedifferentiated and poorly differentiated chordomas are associated with an aggressive clinical course. Further diagnostic implications are discussed herewith.

In today’s era, limb salvage surgery is the procedure of choice and current standard of care in appropriately selected patients of bone sarcomas. For adequate oncologic clearance, preoperative evaluation of the extent of tumor is mandatory. The present study was done to compare measurements of bone sarcomas (osteosarcoma, Ewing’s sarcoma, and chondrosarcoma) as determined by magnetic resonance imaging (MRI) with the histopathological extent seen on resected specimens. We prospectively evaluated 100 consecutive patients with a diagnosis of bone sarcoma who underwent limb salvage surgery between May 2014 and December 2014. The maximum longitudinal (cranio-caudal) dimension of tumor on the noncontrast T1-WI sequence of MRI (irrespective of whether it was pre/postchemotherapy) was compared with the gross dimensions of the tumor on histopathology. The arithmetic mean difference, Wilcoxon signed-rank test, and Spearman’s correlation analysis were used to test the differences and correlation between groups. Mean tumor size on MRI based on the largest extent on MRI was 12.1 ± 4.85 cm (mean ± standard deviation), while it was 10.77 ± 4.6 cm (mean ± standard deviation) on histopathology. In 79 cases, MRI overestimated the extent of disease; the mean was 1.79 cm with a standard deviation of 1.56 cm. When the disease extent was underestimated on MRI (13 cases), the mean was 0.58 cm with a standard deviation of 0.43 cm. In 8 cases (osteosarcoma (7), Ewing’s sarcoma (1)), MRI measurement was equal to histopathology. The Spearman correlation analysis showed a high correlation of tumor length on histopathology with the MRI for all patients (R = 0.948, P

Background: The COVID-19 pandemic accelerated the widespread adoption of digital pathology (DP) for primary diagnosis in surgical pathology. This paradigm shift is likely to influence how we function routinely in the postpandemic era. We present learnings from early adoption of DP for a live digital sign-out from home in a risk-mitigated environment. Materials and Methods: We aimed to validate DP for remote reporting from home in a real-time environment and evaluate the parameters influencing the efficiency of a digital workflow. Eighteen pathologists prospectively validated DP for remote use on 567 biopsy cases including 616 individual parts from 7 subspecialties over a duration from March 21, 2020, to June 30, 2020. The slides were digitized using Roche Ventana DP200 whole-slide scanner and reported from respective homes in a risk-mitigated environment. Results: Following re-review of glass slides, there was no major discordance and 1.2% (n = 7/567) minor discordance. The deferral rate was 4.5%. All pathologists reported from their respective homes from laptops with an average network speed of 20 megabits per second. Conclusion: We successfully validated and adopted a digital workflow for remote reporting with available resources and were able to provide our patients, an undisrupted access to subspecialty expertise during these unprecedented times.