Clinicopathological Study of Chronic Kidney Disease of Unknown Etiology in Odisha.

INTRODUCTION: Chronic kidney disease (CKD) is emerging as a serious health problem in Odisha, India. A new form of severe CKD affecting adults, not due to traditional risk factors like diabetes, hypertension, glomerulonephritis, has been reported in Sri Lanka, Central America, and Egypt in the last two decades. This has been named CKD of unknown origin (CKDu), and it is fatal due to late recognition and rapid disease progression. The aim of the study was to elucidate the association between different sociodemographic, and biochemical parameters with renal morphology in CKD of unknown origin patients. METHODS: A cross-sectional study was conducted on 124 consecutive patients with CKD from the period January 2018 to December 2018. Patients in the age group 18-60 years who met clinical criteria for CKD were included. Participants answered a questionnaire. After the necessary history, clinical evaluation, and blood and urine analyses, a kidney biopsy was undertaken. Kidney biopsy was feasible in 51 patients as the rest 61 patients had shrunken kidneys and 12 patients did not give consent. Patients with diabetes mellitus (DM), hypertension, glomerulonephritis, polycystic kidney disease, obstructive kidney disease or any other congenital diseases, snakebite, pregnancy, malignancy, gout, primary hyperparathyroidism, infectious diseases like human immunodeficiency virus (HIV), TB, Hepatitis B and C, malaria, syphilis, leprosy and coagulopathies were excluded. Among the 51 patients, 23 had CKDu, 25 had chronic glomerulonephritis and three biopsies were inconclusive. RESULTS: The mean age of CKDu patients was 36.78 ± 9.85 years. Males (73.9%) were predominantly affected. A family history of CKD was seen in 82.6% of CKDu cases. Hyponatremia and hypokalemia were predominant biochemical abnormalities in our CKDu cases. Binary logistic regression showed rural residence, family history of CKD, exposure to smoke from burning coal, charcoal, or biomass fuels, low socioeconomic status, and low body mass index were strongly associated with CKDu. There was an increased risk of developing CKDu in persons with a family history of CKD [p = 0.003, odds ratio (OR)- 17.58], persons exposed to smoke from burning coal, charcoal or biomass fuels (p = 0.003, OR- 32.4), and patients with low socio-economic status (p = 0.001, OR- 15.87). Interstitial fibrosis (IF), interstitial inflammation with mononuclear infiltration, tubular atrophy (TA), and global glomerulosclerosis (GS) were pertinent histopathological findings in our study. CONCLUSION: There is no strong evidence for a single cause for CKDu, and multiple environmental, occupational and social factors are probably involved. We need to design consistent and comparative multisite studies to identify etiologies of CKDu, across high-risk populations that may help elucidate the importance of region-specific vs global risk factors.

Guidelines for various laboratory sections in view of COVID-19: Recommendations from the Indian Association of Pathologists and Microbiologists.

Declared as a pandemic by WHO on March 11, 2020, COVID-19 has brought about a dramatic change in the working of different laboratories across the country. Diagnostic laboratories testing different types of samples play a vital role in the treatment management. Irrespective of their size, each laboratory has to follow strict biosafety guidelines. Different sections of the laboratory receive samples that are variably infectious. Each sample needs to undergo a proper and well-designed processing system so that the personnel involved are not infected and also their close contacts. It takes a huge effort so as to limit the risk of exposure of the working staff during the collection, processing, reporting or dispatching of biohazard samples. Guidelines help in preventing the laboratory staff and healthcare workers from contracting the disease which has a known human to human route of transmission and high rate of mortality. A well-knit approach is the need of the hour to combat this fast spreading disease. We anticipate that the guidelines described in this article will be useful for continuing safe work practices by all the laboratories in the country.

Clear cell lesions in pathology: Histomorphologic approach to diagnosis.

There has been remarkable progress in the field of surgical pathology; however, histomorphology has remained the most important and essential tool of the surgical pathologist in everyday practice till now. It is surprising that the hematoxylin-eosin (H and E) stain, introduced more than a century ago, has still remained the gold standard stain for histological examination and diagnosis of human diseases. Besides different findings or clues observed in histopathology sections like inclusions, granules, grooving, globules, halo, or clearing, which would enable the pathologist to provide a precise and accurate diagnosis; observation of clear cells is one of the important findings and clue for reporting. It may also sometimes lead to difficulties and delays in establishing the diagnosis. It can be focal or extensive and primary or rarely it may be secondary. Clear cell changes may be observed in many non-neoplastic, benign, or malignant tumors of diverse origin. Clear cell tumors contain a preponderance of clear cells. It can be seen in almost all the organs of human body and can be classified according to location or biological behavior. Commonly seen clear-cell tumors are usually malignant and common organs involved are female genital tract, urogenital tract, head and neck areas, central nervous system, skin, and rarely in bone and soft tissues. For approach to clear cell lesions, one has to decide if the change is artifactual, a mimic of clear cell tumors, or a clear cell tumor in reality. Once the mimics and artifactual/degenerative changes have been ruled out, a tumor either primarily of clear cell origin or showing secondary change has to be decided. The tumor next is to be diagnosed as benign/malignant and epithelial/mesenchymal based on morphology.

Differential expression of cyclin E, p63, and Ki-67 in gestational trophoblastic disease and its role in diagnosis and management: A prospective case-control study.

BACKGROUND: Gestational trophoblastic disease (GTD) constitutes a spectrum of tumors and tumor-like conditions, characterized by proliferation of pregnancy-associated trophoblastic tissue of progressive malignant potential. It is very difficult to differentiate these complex groups of lesions basing on histomorphology alone. Immunohistochemistry (IHC) with cyclin E, P63, and Ki-67 has a definite role in the identification of different trophoblasts and entities of GTD and also in the determination of biological behavior. AIMS: The aim of this study is to find the differential expression of cyclin E, p63, and Ki-67 in normal placenta, hydropic abortus (HA), and various entities of GTD. DESIGN AND SETTINGS: A prospective case-control study conducted in a government medical college. METHODS: Total 96 cases, divided into Group A (48 histologically confirmed cases of GTD) and Group B (controls comprising 8 HA and 40 normal placentas of different trimesters), were studied. The histological samples were subjected to IHC using cyclin E, Ki-67, and p63. STATISTICAL ANALYSIS: Results were analyzed using SPSS statistical method. RESULTS: Among the three immunomarkers used, Cyclin E and Ki-67 show statistically significant difference (P < 0.05) when compared between GTD and control groups, but it was insignificant for p63 (P = 0.369). Strong staining intensity of cyclin E and Ki-67 is seen in complete moles, choriocarcinoma, and placental site trophoblastic tumor. CONCLUSION: This study was done to evaluate the role of cell cycle regulatory proteins such as cyclin E and p63 and proliferation marker Ki-67 in the detection of various trophoblasts and differential diagnosis of the lesions associated with them.

Trucut Biopsy vs FNAC of Pelvic Tumors-Who Wins the Match?

Preoperative pathologic diagnosis of pelvic tumors is mandatory for proper management of patients like neoadjuvant chemotherapy and interval debulking. Currently there are many minimally invasive methods available which include fine-needle aspiration cytology (FNAC) and trucut biopsy, mostly complimentary to each other. FNAC is a cheap, rapid and sensitive method for diagnosis of pelvic tumors. It can be done as an outpatient procedure without complications. But with it, the tissue architecture cannot be seen. Trucut biopsy on the other hand reveals tissue architecture and can help in grading and subtyping of malignant tumors. Trucut biopsy has to be done under image guidance like ultrasound and computed tomography. Patient is administered local anaesthetic and can be discharged safely after 2 hours. Pathologists familiar with histomorphology can give a correct diagnosis easily. But many times sampling errors may occur; especially in large tumors, resulting only in necrosis, hemorrhage and degenerated tissue bits. Also differentiation of borderline from malignant ovarian tumors is very difficult. In case of mixed tumors one component may be missed. Hard tumors like fibromas and leiomyomas yield scanty material and result in inadequate reporting. With FNAC, the overall accuracy rate is estimated to be around 96.3%. With trucut biopsy, adequacy is from 91 to 95% and accuracy is approximately 98% in different studies. When both methods are combined, the adequacy is 100%, diagnostic accuracy 95.5%, sensitivity 94.9% and specificity 100%. Therefore depending on the clinical diagnosis and the location of tumors, either FNAC and/or trucut biopsy can be chosen.

Serous Tubal Carcinogenesis: The Recent Concept of Origin of Ovarian, Primary Peritoneal and Fallopian Tube High-Grade Serous Carcinoma.

Background: Pelvic (non-uterine) high-grade serous carcinomas (PHGSC) including ovarian, tubal and primary peritoneal serous carcinomas have increased death: incidence ratio due to presentation at advanced stage, rapid progression, poor prognosis and high morbidity. Ambiguity regarding their pathogenesis and lack of a proper screening method is the cause of their late detection and high fatality rate. This study was undertaken to assess the fallopian tube for the presence of precursor lesions in pelvic serous carcinoma. Methods: This was a prospective case-control study carried out in a tertiary care center. Consecutive specimens of 55 cases of pelvic high-grade serous carcinoma and 41 controls inclusive of 21 low-grade serous carcinoma, 10 benign adnexal masses and 10 normal adnexa were included in the study. Both side fallopian tubes in each case were subjected to histopathological examination and p53, Ki67 immunohistochemistry. Results: There were 55 cases of PHGSC comprising of 50 cases of ovarian HGSC, two cases of primary peritoneal carcinoma (PPC) and three cases of tubal carcinoma. Serous tubal intraepithelial carcinoma (STIC) was detected in 14 cases (28%), p53 signature in 13 cases (26%) and tubal intraepithelial lesion in transition in 10 cases (20%) of ovarian HGSC. One case (50%) of PPC and one (33%) case of tubal carcinoma revealed the presence of STIC. None of the controls exhibited any precursor lesion except ovarian low-grade serous carcinoma where p53 was detected in 20% of cases. Conclusion: This revelation concludes that fallopian tubes are the sites of precursors of PHGSC to a large extent. In the absence of a proper screening method of HGSC, prophylactic bilateral salpingectomy at hysterectomy for benign diseases can achieve ultimate goal of reduction in incidence of PHGSC.

Poorly Differentiated Sertoli-Leydig Cell Tumour of Ovary with Heterologous Elements.

Sertoli-Leydig Cell Tumour (SLCT) is included under sex-cord stromal tumour of testis or ovary. Ovarian pathology is an extremely rare entity constituting less than 0.5% of all ovarian neoplasms. Majority of the cases present at younger age group, i.e., 2nd and 3rd decade of life. The clinical presentation depends on either mass effect or excess hormone production. Virillization symptoms are the most common presentation and depend upon the quantity of androgen production. Most of the patients have a unilateral mass without extraovarian spread and present at stage-I. Treatment and prognosis depends on the degree of the differentiation and the stage of the disease. Here, we report a case of SLCT of the ovary in a young female. The patient initially presented with pain abdomen due to mass effect and was treated with conservative surgery followed by adjuvant chemotherapy due to the presence of poorly differentiated pathology with heterologous elements.

Cytologic Interpretation of Melanotic Neuroectodermal Tumour of Infancy Involving Cranial Bones: Clue to Diagnosis.

Melanotic neuroectodermal tumour of infancy (MNTI) is a rare, benign but locally aggressive neoplasm of infants commonly affecting the maxilla. It can also involve other areas like skull, mandible, brain and epididymis. The tumour comprise of dual populations of cells like small, basophilic neuroblast like cells and large pigment laden epithelial cells arranged in tubular and pseudoglandular pattern. The proportion of two components varies and therefore the diagnosis can be difficult in absence of the large cells. We describe the cytologic, histologic and immunohistochemical findings in a case of MNTI involving left side orbit with frontal, temporal and parietal bones. The cytologic interpretation could be made due to the suggestive clinical and radiologic findings and detection of large epithelial pigmented cells on thorough searching. The neuroblast like cells was positive for Neuron specific enolase, large cells for HMB-45 and Pan CK. Both the cellular components were negative for desmin. This case report is presented due to its rarity and also to aid the surgical pathologists in diagnosis where the findings are not too straight forward.

Intra-operative cytodiagnosis of primary ovarian choriocarcinoma with Ki67 immunoexpression.

Primary ovarian choriocarcinoma is a rare neoplasm that can be gestational and non-gestational in origin. It accounts for one in 369 million pregnancies. Both types present with similar clinical, histomorphological and ultrastructural findings. But, it is essential to differentiate the two because the gestational type has a better clinical course and responds to single-agent chemotherapy. Usually, the gestational ovarian choriocarcinoma is metastatic from uterine choriocarcinoma and follows antecedent pregnancy and is seen in females of 40 years or older. DNA polymorphism analysis showing the presence of paternal genes in the tumor establishes the gestational origin of choriocarcinoma. We present the intra-operative cytological findings of a case of primary ovarian choriocarcinoma in a 25-year-old lady arising from ectopic pregnancy with Ki67 immunostain.

Risk factors, organ weight deviation and associated anomalies in neural tube defects: A prospective fetal and perinatal autopsy series.

INTRODUCTION: Neural tube defects (NTD) are a group of serious birth defects occurring due to defective closure of neural tube during embryonic development. It comprises of anencephaly, encephalocele and spina bifida. We conducted this prospective fetal autopsy series to study the rate and distribution of NTD, analyze the reproductive factors and risk factors, note any associated anomalies and evaluate the organ weights and their deviation from normal. MATERIALS AND METHODS: This was a prospective study done over a period of 6 years from August, 2007 to July, 2013. All cases of NTDs delivered as abortion, still born and live born were included. The reproductive and risk factors like age, parity, multiple births, previous miscarriage, obesity, diabetes mellitus, socioeconomic status and use of folic acid during pregnancy were collected.Autopsy was performed according to Virchow's technique. Detail external and internal examination were carried out to detect any associated anomalies. Gross and microscopic examination of organs were done. RESULTS: Out of 210 cases of fetal and perinatal autopsy done, 72 (34.28%) had NTD constituting 49 cases of anencephaly, 16 spina bifida and 7 cases of encephalocele. The mothers in these cases predominantly were within 25-29 years (P = 0.02) and primy (P = 0.01). Female sex was more commonly affected than males (M:F = 25:47, P = 0.0005) There was no history of folate use in majority of cases. Organ weight deviations were >2 standard deviation low in most of the cases. Most common associated anomalies were adrenal hypoplasia and thymic hyperplasia. CONCLUSION: The authors have made an attempt to study NTD cases in respect to maternal reproductive and risk factors and their association with NTD along with the organ weight deviation and associated anomalies. This so far in our knowledge is an innovative study which was not found in literature even after extensive search.

Cervical strongyloidiasis in an immunocompetent patient: A clinical surprise.

A 32-year-old lady came for a routine gynecological check up. Her cervical cytologic smear was reported as low grade squamous intraepithelial lesion. As a part of basic routine investigation, cervical punch biopsy was done. Astonishingly it revealed multiple rhabditiform larvae of Strongyloides stercoralis. These were curved thick with pointed end and a short buccal cavity. She did not have any history of immunosuppression including steroid therapy and was otherwise normal. Extensive review of the literature on parasites encountered in cervix yielded few case reports on strongyloides in cytologic smears, but failed to reveal any report till date on S. stercoralis found in histopathology section. Our case is probably the first in the world and the first reported from India to the best of our knowledge. We describe this case of strongyloidiasis of cervix with review of the literature on various parasites encountered in the cervix because of its rarity and also to keep this parasitic infestation as a differential diagnosis of cervical lesions.

Cytodiagnosis of metastatic Ewing's sarcoma of orbital mass and its confirmation by demonstration of EWS/friend leukemia integration 1 fusion gene.

Ewing's sarcoma (EWS) is an undifferentiated sarcoma of bone. Its morphologic appearance resembles many other malignant small round cell tumors. Due to the morphologic overlap, there is diagnostic difficulty and for accurate diagnosis, requires special studies such as immunohistochemistry, electron microscopy, cytogenetics, and molecular genetic analysis. We report a case of metastatic EWS from orbital mass in a 14-year-old female child diagnosed by cytology after clinicopathologic evaluation. She presented with low back ache of 1 year followed by proptosis of the right eye and swelling of the right side chest wall. Cytosmear and Tru-cut biopsy was taken from the orbital mass showed features of EWS. It was confirmed later by further studies including demonstration of EWS/friend leukemia integration-1 fusion gene by molecular genetic analysis.

Cryptococcal lymphadenitis in HIV: a chance diagnosis by FNAC.

Cryptococcosis is a life threatening, opportunistic fungal disease in human immunodeficiency virus-infected individual. Lymph node involvement as a presenting feature in Cryptococcosis is not a common manifestation. A prompt diagnosis is of utmost importance in this disseminated form of cryptococcosis. There are very few reports, however, of cryptococcal lymphadenitis as a presenting feature. We report here a case of cryptococcal lymphadenitis that was diagnosed by fine-needle aspiration cytology of the involved cervical lymph node.

Cytodiagnosis of angiosarcoma of breast.

A 24-year-old female presented with swelling in the left breast for one-and-a-half years associated with pain for last 4 months. During this period, she was operated twice and once again there was local recurrence, the biopsy was interpreted as benign vascular lesion. The case was diagnosed by preoperative cytology as angiosarcoma of breast, after which, she underwent modified radical mastectomy. Angiosarcoma of breast is uncommon with extremely bad prognosis. Familiarity with the clinical and pathologic features is critical in avoiding underdiagnosis and delayed treatment.