Non-dysraphic extramedullary intradural spinal lipoma with neurocutaneous melanocytosis.

INTRODUCTION: Intradural spinal lipomas are very rare and constitute less than 1% of all spinal tumors. Such tumors are usually associated with spinal dysraphism and occur mostly in the lumbosacral or cervical region. Intradural spinal lipomas tends to be intramedullary or subpial. Meningeal melanocytoma is further rarer cases that comprise less than 0.1% of cases. These usually occur in the fifth or fifth decade and chances of malignant transformation are high. CASE REPORT: Here, we report an extremely rare case (first to the best of our knowledge) of a 9 years female child who presented to us with rapid progressing paraparesis. She was operated and found to have an intradural purely extramedullary spinal lipoma without spinal dysraphism. Moreover, she had melanin pigment deposits all over her meninges which is further rare. On presentation, the patient was bedridden but after surgery, the patient improved and could walk without support. CONCLUSIONS: To the best of our knowledge, this is the first case of spinal cord lipoma in dorsal location along with melanin pigments in the meninges. We discuss the pathogenesis, presentation and management of intradural extramedullary spinal lipomas.

Fetal phenotypes of Mendelian disorders: A descriptive study from India.

OBJECTIVE: Exome sequencing (ES)-based diagnosis of Mendelian diseases in the fetus is limited by paucity of phenotypic information. This study reports the comprehensive phenotypes of some fetuses with Mendelian disorders. METHODS: Next generation technology-based sequencing of all coding regions of the genome (Exome sequencing) or targeted gene sequencing using Sanger or next generation platforms was performed in a cohort of deeply phenotyped, cytogenetically normal fetuses with morphological defects. Prenatal ultrasonographic phenotypes and postmortem details including dysmorphology, histopathology, and radiography were ascertained. Novel candidate genes, novel/unusual findings, and unusual genotypes in cases with confirmed Mendelian disorders are described. RESULTS: Of the 102 fetuses sequenced, 45 (44%) achieved definitive diagnosis of a Mendelian disorder with 50 pathogenic/likely pathogenic variants. The majority (87%) were autosomal recessive, 69% families were consanguineous, and 54% variants were novel. Dysmorphic syndromes, skeletal dysplasias, and metabolic disorders were the commonest disease categories, ciliopathies and dystroglycanopathies, commonest molecular categories. We describe the first fetal description of six monogenic diseases, and nine cases with novel histological findings. Nineteen cases had novel/unusual findings. CONCLUSION: This cohort demonstrates how deep fetal phenotypes of some Mendelian disorders can show novel/unusual findings, which have important implications for prenatal diagnosis of these conditions.

Development and Prospective Validation of the Levothyroxine Dose Prediction Model in Primary Hypothyroidism.

Multiple visits are needed to achieve euthyroidism on levothyroxine in newly detected primary hypothyroidism. We aimed to develop a levothyroxine dose estimation algorithm for primary hypothyroidism. Adults with newly diagnosed hypothyroidism were enrolled prospectively, first in the training cohort, followed by the validation cohort separated by time and person. We developed a predictive algorithm from Training Cohort and validated the model in Validation Cohort. Training Cohort: In this cohort, 358 subjects (259 women and 99 men) were enrolled. The median duration needed to achieve euthyroidism was 4±0.5 months. The mean levothyroxine daily dose was 60.5±34.1 µg. Data of euthyroid subjects within 6 months of treatment initiation and age range 18-65 years were used for algorithm development. In the multivariable linear regression algorithm, pretreatment serum thyrotropin level, and sex formed the best-fit predictive model (adjusted R2 0.73, p-value <0.001). Validation Cohort: Eighty-four subjects (61 women and 23 men) were enrolled and started on an estimated levothyroxine dose derived from the developed prediction model. On the first follow-up on treatment, 34/50 participants achieved euthyroidism (68%) at 1.5 months. In conclusion, the proposed prediction model for levothyroxine dose estimation effectively achieves early euthyroidism in two-third subjects in the age range of 18-65 years.

Exome sequencing for perinatal phenotypes: The significance of deep phenotyping.

OBJECTIVE: To ascertain the performance of exome sequencing (ES) technology for determining the etiological basis of abnormal perinatal phenotypes and to study the impact of comprehensive phenotyping on variant prioritization. METHODS: A carefully selected cohort of 32/204 fetuses with abnormal perinatal phenotypes following postmortem/postnatal deep phenotyping underwent ES to identify a causative variant for the fetal phenotype. A retrospective comparative analysis of the prenatal versus postmortem/postnatal phenotype-based variant prioritization was performed with aid of Phenolyzer software. A review of selected literature reports was done to examine the completeness of phenotypic information for cases in those reports and how it impacted the performance of fetal ES. RESULTS: In 18/32 (56%) fetuses, a pathogenic/likely pathogenic variant was identified. This included novel genotype-phenotype associations, expanded prenatal phenotypes of known Mendelian disorders and dual Mendelian diagnoses. The retrospective analysis revealed that the putative diagnostic variant could not be identified on basis of prenatal findings alone in 15/22 (68%) cases, indicating the importance of comprehensive postmortem/postnatal phenotype information. Literature review was supportive of these findings but could not be conclusive due to marked heterogeneity of involved studies. CONCLUSION: Comprehensive phenotyping is essential for improving diagnostic performance and facilitating identification of novel genotype-phenotype associations in perinatal cohorts undergoing ES.

Exome sequencing identifies novel ACE splice-site variant in a fetus with renal tubular dysgenesis.

We report a 32-week fetus conceived of consanguineous parentage which presented with severe early onset oligohydramnios and history of a similarly affected sibling in previous pregnancy. Ultrasonography and autopsy were inconclusive, prompting exome sequencing on fetal DNA. This resulted in identification of a homozygous novel 3' splice-site variation in intron 17 of the ACE gene (NM_000789.3:c.2642-1G>A), confirming diagnosis of autosomal recessive renal tubular dysgenesis, and facilitating prenatal diagnosis in subsequent pregnancy.

Pilomatricoma: An unusual cause of lump in a male breast.

We present the case of a 48-year-old man who presented with a painless, progressively increasing lump in the left breast. The mammographic and sonographic appearance of the lesion was suspicious for malignancy. Fine needle aspiration cytology and histopathologic examination confirmed the diagnosis of pilomatricoma. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:209-211, 2018.

A Dysmorphology Based Systematic Approach Toward Perinatal Genetic Diagnosis in a Fetal Autopsy Series.

BACKGROUND: This retrospective study assesses the contribution of genetic disorders in fetuses undergoing postmortem evaluation and the performance of a clinical dysmorphology based systematic approach toward genetic diagnosis. MATERIALS AND METHODS: Ninety fetuses, including spontaneous losses and terminated pregnancies, underwent a postmortem evaluation including dysmorphological examination, radiological studies, and histopathological examination. Genetic testing including karyotyping, biochemical testing, Sanger sequencing, and exome sequencing were performed selectively. RESULTS: A genetic etiology was concluded in 48 fetuses (55%). As a standalone test, dysmorphological examination was able to ascertain a definite genetic diagnosis in sixteen cases, histopathology in six; and karyotyping, biochemical testing and exome sequencing in two cases each (Total 28). Additionally, dysmorphology findings indicated possible genetic disorder in 20 cases. CONCLUSION: Genetic etiologies contribute significantly to fetuses undergoing autopsy in this series. A systematic approach to postmortem fetal evaluation guided by dysmorphological examination provides high diagnostic yield toward perinatal genetic diagnosis.

An Unusual Encounter: Microfilaria Incidentally Detected in the Bone Marrow Aspirate of a Chronic Kidney Disease Patient.

Lymphatic filariasis is endemic in a few states of India and is one of the most common public health concerns. Wuchereria bancrofti (W. bancrofti) is the most common parasite that causes lymphatic filariasis in India. Microfilariae have been commonly found in the peripheral blood and body fluid, as well as demonstrated in fine needle aspirates (FNA) and bronchial cytology. They have been rarely reported in bone marrow aspirates. Due to the nocturnal periodicity of W. bancrofti, it may be missed in peripheral blood during the day. Though peripheral eosinophilia is a presenting feature of filariasis, it may be absent in the majority of cases, as in this case. We report an incidental finding of W. bancrofti in the bone marrow aspirate of a 72-year-old male who had chronic kidney disease.

Ethical Considerations in Post-Mortem Sperm Retrieval: A Comprehensive Review.

This comprehensive review delves into the moral and ethical dilemmas surrounding post-mortem sperm retrieval (PMSR) and its implications for creating new individuals. The paper examines the challenges posed by unusual requests for sperm retrieval from the deceased's widow and parents, as well as the broader socio-ethical considerations associated with PMSR. These requests have often been denied due to the absence of established laws and guidelines governing posthumous sperm retrieval and subsequent births, which were once deemed impossible. While some countries have implemented institutional policies to regulate its use to some extent, there remains a lack of standardized rules and procedures for the collection and retrieval of sperm after death. It is essential to introduce institutional guidelines to facilitate requests for assisted reproductive technology (ART) following successful sperm retrieval. Additionally, the development of PMSR legislation is necessary to ensure a proper balance between the moral rights and fundamental rights of the deceased, their family, and any current or future offspring, while providing adequate protection for all parties involved.

Cytohistological findings and diagnostic challenges in rare pediatric pulmonary mesenchymal malignancies: A report of two cases.

Pulmonary mesenchymal tumors are uncommon neoplasms and the data available on their clinical, cytohistomorphological, immunohistochemical, and molecular findings are limited, leading to difficulty in timely diagnosis and management. Case 1: A 12-year-old boy presented with a right endobronchial mass. Imprint smears from endobronchial biopsy revealed moderately pleomorphic spindle cell tumor arranged in fascicles and perivascular pattern with attached myxoid material showing occasional mitotic activity suggesting a cytological diagnosis of sarcoma. Biopsy also displayed similar morphology. Extensive immunohistochemistry (IHC) showed diffuse SMA, focal AE1/AE3, and diffuse ALK positivity along with a MIB/Ki67 index of 30%-40% leading to the diagnosis of inflammatory myofibroblastic tumor (IMT; Sarcoma grade). Case 2: A 8-year-old boy presented with a huge left-sided mass replacing the entire lung parenchyma and eroding adjoining ribs. Pleural fluid cytology revealed vague clusters of PAS-positive diastase-sensitive small atypical cells with associated inflammatory cells in the hemorrhagic background, suggesting a diagnosis of malignant small round blue cell tumor. Trucut biopsy from the mass showed spindled to round cells showing diffuse positivity with CD99 and BCL-2. Molecular studies with reverse transcription-PCR (RT-PCR) for SYT-SSX and EWS-FLI1 were negative for synovial sarcoma and Ewing's sarcoma, respectively. Given the clinical setting, PAS positivity, IHC, and molecular studies, the diagnosis of tumors of uncertain differentiation with the possibility of Ewing's sarcoma family of tumors (ESFT) with a translocation between EWS1 and other ETS-family members (ERG, FEV, ETV1, E1AF, etc.) was suggested.

Predictive ability of complete blood count, mean platelet ratio, mean platelet volume, and neutrophil/lymphocyte ratio for severe pneumonia among RT-PCR or radiologically proven COVID-19 patients.

Background: Immuno-inflammatory markers related to white blood cells, and platelets are shown to be associated with COVID-19 infection, and considered to be independent markers for clinical outcomes and mortality. The present study aimed to study the predictive value of these hematologic parameters in progression of COVID-19 to severe pneumonia. Methods: This was an analytical cross-sectional study conducted among RT-PCR or radiologically proven COVID-19 patients in a tertiary care hospital in Rajasthan. Semi-structured questionnaire was used to collect the epidemiological information of the patients with COVID-19. Complete blood count and other laboratory parameters were also studied among the patients. Results: Mean age of participants in the study was 52 years, with about 70% being males. Cough and breathlessness were the most common symptoms among the patients. It was found that the parameters related to white blood cells were significantly different between patients with COVID-19 infection and severe pneumonia (except absolute monocyte count). NLR was significantly higher among those with severe pneumonia. In the univariate analysis, age (OR - 1.02), NLR (OR - 1.16), and albumin (OR - 0.45) were found to be significant predictors of progression to severe pneumonia. In the final model, adjusted for confounders, only NLR and albumin levels significantly predicted progression to severe pneumonia among COVID-19 patients. Conclusion: The study consolidates the predictive ability of NLR for severe pneumonia. It is an important finding, as health facilities with limited access to laboratory investigations can rely on simple markers in routine practice to predict the progression of COVID-19 infection to severe pneumonia.

Extra Nasopharyngeal Angiofibroma Arising From Oropharynx: A Clinical Report.

Angiofibroma arising from sites other than nasopharynx is rare and termed as Extra nasopharyngeal angiofibroma (ENA). ENAs commonly arise from nasal septum, maxillary sinus, and inferior turbinate. But angiofibroma arising from oropharynx have not been frequently reported. We present here a case of middle-aged male who presented with a large pedunculated oropharyngeal mass attached to palatopharyngeal fold. Endoscopic radiofrequency assisted transoral excision of mass was done. Histopathological features were consistent with angiofibroma arising from oropharynx. Patient recovered well with no evidence of recurrence till 18 months of follow up. In this report, we have tried to emphasize the diagnostic workup for oropharyngeal mass. This report also provides an insight into the clinical and pathological behavior of extra nasopharyngeal angiofibroma.

Extensive mucoepidermoid carcinoma-like differentiation in follicular carcinoma of the thyroid.

Mucoepidermoid carcinoma (MEC) is a rare malignant thyroid neoplasm. Cases of MEC with papillary, insular, and anaplastic thyroid carcinoma have been reported. Here, we present a case of follicular carcinoma with extensive MEC-like differentiation. A 62-year-old female presented with complaint of thyroid swelling for 10 years. Cytological features were suggestive of follicular neoplasm. Contrast-enhanced computed tomography showed metastasis to lung and vertebrae. Salivary glands and breasts were normal on examination and imaging. Subtotal thyroidectomy with bilateral neck dissection surgery was performed. The specimen was submitted for histopathological examination. Microscopy showed features of follicular carcinoma with capsular and vascular invasion along with an additional MEC-like morphology. Follicular carcinoma with extensive MEC-like differentiation is a rare observation. Since the tumor was sparing salivary glands and breasts, we considered it as mucoepidermoid differentiation over a collision tumor. However, immunohistochemistry and molecular analysis were the limitations.

Cytologic and flowcytometric findings in a case of myelomatous pleural effusion: A rare and ominous presentation of multiple myeloma.

Plasma cell myeloma is a hematologic malignancy characterized by multifocal clonal proliferation of plasma cells usually associated with M protein secretion in serum and/or urine and evidence of organ damage. Generally, the presenting features are related to anemia, bone lesions, and renal failure. Pleural effusion is rare in multiple myeloma and when present is often due to nonmalignant causes. Myelomatous pleural effusion that is, effusions directly due to pleural infiltration by plasma cells is even rarer. We present a case of a patient presenting with dyspnea due to myelomatous pleural effusion. The fluid in such a case may be subjected to cytology examination, protein electrophoresis, flowcytometric analysis, and cytogenetics. The case highlights the utility of cytomorphology and flowcytometry in the diagnosis of myelomatous pleural effusion and also highlights that this type of presentation portends a poor prognosis to the patient.

Histopathologic spectrum and clinical correlation of lesions of jaw - a series of 60 cases.

Odontogenic tumors have the potential for the development of malformations of the teeth as well as the surrounding tissue. Sound knowledge of various types of jaw lesions and their characteristics will help the clinician with timely measures and management. Our main aim was to study the histopathological nature of various jaw lesions retrieved from biopsies and resected specimens. Consecutive 60 cases of jaw lesions were analyzed. Odontogenic cyst, odontogenic tumor, fibro-osseous lesions, and giant cell lesions were included in this study. Lesions of the oral cavity, soft tissue lesions, secondary and inflammatory lesions of the jaw were excluded. H&E stained slides were examined by light microscopy. A total of 60 jaw lesions were analyzed for histologic type. Odontogenic cysts (55%) were found to be most common followed by odontogenic tumors (25%), fibro-osseous lesions (10%), giant cell lesions (05%), and non-odontogenic cysts (05%). The most commonly affected age groups were between 20-40 years. The mandible was more commonly involved bone. To conclude, based only on histology, the distinction between odontogenic cysts is difficult and almost impossible when they are secondarily infected. For definitive diagnosis clinical-radiological correlation is needed.

Clinical, Virological, and Pathological Profile of Patients Who Died of COVID-19: An Autopsy-Based Study From India.

Background and objective Ever since its emergence in December 2019, coronavirus disease 2019 (COVID-19) has affected more than 220 million people worldwide, resulting in more than 45 million deaths. The present autopsy-based study was undertaken to understand the pathophysiology of the disease and correlate the histopathological and virological findings with the antemortem clinical and biochemical determinants. Methods In this prospective observational study, autopsies were carried out on 21 reverse transcription-polymerase chain reaction (RT-PCR)-proven COVID-19 patients who had died of the disease. The histopathological findings of tissue samples from lungs, liver, and kidneys collected during the autopsy were graded based on their presence or absence; if present, they were graded as either focal or diffuse. The findings were correlated with antemortem clinical and biochemical findings. Postmortem tissue RT-PCR analysis was conducted, and findings were compared with postmortem histopathological findings. Results There was multisystem involvement with the COVID-19 cases. The involvement of lungs was observed in most of the cases (90.4%). The presence of viral RNA was observed in all the organs including the liver (57.1%) and kidney (66.6%). An association was observed between antemortem biochemical parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT)] and the histopathological features in the liver. No correlation between the Sequential Organ Failure Assessment (SOFA) score recorded clinically and lung histopathology was observed; nor was there any correlation between blood urea-creatinine levels and kidney histopathology. Conclusions Our study shows that COVID-19 is a multisystemic disease and the mortality associated with it is likely to be multifactorial. Despite the presence of amplifiable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various organs, no association could be established between the clinical and histopathology findings. Neither the duration of hospitalization nor the duration of mechanical ventilation showed any correlation with the severity of histopathological findings in the lungs at autopsy.

Human sodium iodide symporter (hNIS) in fibroadenoma breast--a immunohistochemical study.

Human sodium iodide symporter (hNIS), responsible for the active transport of iodine is an integral plasma membrane glycoprotein present in the thyroid cells and extrathyroid tissues like breast and salivary glands. If its functional form is unequivocally shown in benign or malignant breast tissues, then it may serve as a basis for diagnosis and treatment using radioactive iodine. With an aim to analyze the hNIS expression in a distinct benign breast condition of fibroadenoma, biopsy proven fibroadenoma tissues, normal non-lactating breast tissue and biopsy proven infiltrating duct carcinoma tissues were examined for hNIS expression using immunohistochemistry. Out of 20 biopsy proven fibroadenoma tissues, 19 (95%) showed positivity for hNIS protein and only one was negative. Of these 10% were mildly positive, 50% cases were moderately positive and 35% showed intense positivity. None of the control tissue obtained from reduction mammoplasty specimens or normal breast tissues samples (5 cms away from the tumor) were positive, hNIS was also intensely positive in 9 out of 10 (90%) infiltrating duct carcinoma tissues and moderately positive in one case. These preliminary results show that hNIS was present in high frequency as demonstrated by immunohistochemistry in fibroadenoma breast.

Synchronous Breast Carcinoma, Uterine Myoma, and Ovarian Teratoma in a Single Woman.

Multiple primary tumors in a patient diagnosed with invasive ductal breast cancer are rarely reported in the literature. Here we present a case of invasive ductal carcinoma of the breast in a 42-year-old lady, with synchronous uterine leiomyoma (UL), ovarian teratoma and with prior history of follicular adenoma of thyroid in the same patient. The clinical presentation and management plan is discussed with a review of the literature. Breast cancer is the most common cancer in women where the concomitant occurrence of multiple primary tumors is a diagnostic and therapeutic challenge. In low- and middle-income countries, where facilities of genetic screening in all patients of synchronous neoplasia are limited due to scarcity of resources, strong clinical suspicion, multidisciplinary management, and follow-up remain important.