Hearts don't lie: Cardiac tuberculosis diagnosed on fine-needle aspiration cytology.

Cardiac involvement in tuberculosis is relatively rare when compared to other organs and often involves the pericardium leading to constrictive pericarditis. Myocardial tuberculoma is exceedingly rare and only seldom cases have yet been reported. Our report is of a case diagnosed on fine-needle aspiration cytology.

Acantholytic Squamous Cell Carcinoma: a Diagnostic Pitfall on Cytology.

Acantholytic squamous cell carcinoma is an infrequent subtype of squamous cell carcinoma. This tumour variant being rare in itself has been rarely described at the penile location, thus leading to a limitation on information of pathological and immunohistochemical findings and prognosis. Clinical observations indicate an aggressive biologic behaviour. The cytological features on fine-needle aspiration cytology samples have rarely been described in literature. It is imperative for pathologists to be aware of the cytological features so as to allow the distinction of this variant from conventional squamous carcinoma. Here, we explore an intriguing case of a metastatic tumour to inguinal lymph node with the primary lesion at the penis which constituted a diagnostic challenge on cytological examination.

Morbidity and Mortality of Necrotizing Fasciitis and Their Prognostic Factors in Children.

Background: This is a prospective study of the clinico-etiologic profile and factors affecting outcomes in 40 children managed for necrotizing fasciitis (NF). Materials and Methods: Demographic details, clinical characteristics, and laboratory parameters were recorded, and the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was calculated. Primary outcome (survival vs. nonsurvival) was noted, and prognostic factors were identified. Results: Initiating factors included boils (45%), i.v. cannula extravasations (22.5%), and blunt trauma (17.5%). Lesion (s) were predominantly on the lower limbs (35%) and trunk (25%). Twenty-two patients (55%) had <5% body surface area (BSA) involved. Severely deranged clinical and laboratory parameters were common. Ultrasound localized fluid collections. Pus cultures showed methicillin-resistant Staphylococcus aureus (52.5%), methicillin-sensitive S. aureus [27.5%], and polymicrobial growth (20%). Blood culture was positive in 24 patients (60%). Most isolates were sensitive to clindamycin and amoxy-clavulanate. Prognostic factors for mortality (n = 6; 15%) included categorization as "Sick," BSA involvement >10%, thrombocytopenia, raised serum creatinine, late debridement, and polymicrobial blood culture isolates. All six nonsurvivors had a LRINEC score of ≥8 and positive blood cultures. Six patients (20.7%) developed unsightly scars and 5 (17.24%) contractures across joints. Conclusions: Pediatric NF has significant morbidity and mortality. Patients with adverse prognostic factors can benefit from early referral to a facility with a critical care unit. Adequate wound management is essential to minimize residual deformity.

Squamous cell carcinoma arising from keratinizing desquamative squamous metaplasia of renal pelvis and double paraneoplastic syndrome: Association of two rare entities.

Keratinizing desquamative squamous metaplasia (KDSM) of the upper urinary tract is a rare entity. The present case is of a 45-year-old female patient with an 8-month history of abdominal lump, recurrent right lumbar pain, intermittent fever, and oliguria. Computed tomography kidney, ureter, and bladder revealed a grossly enlarged right kidney along with heterogeneously enhancing soft tissue density mass and internal septations. A differential diagnosis of renal cell carcinoma, urothelial carcinoma, tuberculosis, and pyonephrosis of the kidney was considered as per the clinical and radiological presentation. Intraoperatively, thick fluid was seen in the kidney and its pedicle was seen adhered to duodenum. Partial nephrectomy was done and on microscopic examination squamous cell carcinoma (SCC) was seen arising in the setting of KDSM. Postoperatively, the patient showed an exponential rise of total leukocyte count (100/153 × 103/µl) and serum calcium levels (10.1/17.2/20.4 mg/dl); eventually started deteriorating and later succumbed to illness. We report this rare association of SCC of the renal pelvis arising in KDSM along with the double paraneoplastic syndrome.

Supernumerary tooth autotransplantation to replace missing maxillary central incisor using three-dimensional replica: A 6-year follow-up.

INTRODUCTION: Tooth autotransplantation is a viable surgical treatment option for patients with missing permanent teeth. Premolars are generally used for autotransplantation but often require extensive modifications. This case report evaluates the use of supernumerary tooth as an alternative option for premolar autotransplantation. This report shows successful supernumerary tooth autotransplantation with 6-year follow-up. METHODS: A 13-year-old male with non-contributory medical history was referred for a missing maxillary left central incisor (#9) and presence of a supernumerary tooth. The clinical and radiographic examination revealed presence of supernumerary tooth with similar dimensions to a central incisor. The treatment plan included autotransplantation of the supernumerary tooth to replace the missing central incisor (short-term) and future implant replacement of the autotransplanted tooth when jaw growth ceases (long-term). The patient and parents consented to treatment. A 3-D tooth replica was constructed based on CBCT analyses. Site #9 was prepared using split ridge technique to create a socket to house the 3-D replica. Upon achieving proper socket form, the supernumerary tooth was extracted and autotransplanted in the prepared socket. The supernumerary tooth was splinted, and the bite opened posteriorly using composite to eliminate any occlusal interferences. RESULTS: The patient was followed up clinically and radiographically. The autotransplanted supernumerary tooth integrated well within the newly created socket and remained functional at the 6-year follow-up. CONCLUSIONS: The current case presents successful management of supernumerary tooth autotransplantation with 6-year follow-up. The results show stable periodontium with satisfactory functional and aesthetic results.

Detection of human papillomavirus infection in oral cancers reported at dental facility: assessing the utility of FFPE tissues.

Incidence of human papillomavirus (HPV)-associated oral cancers is on the rise. However, epidemiological data of this subset of cancers are limited. Dental hospital poses a unique advantage in detection of HPV-positive oral malignancies. We assessed the utility of formalin-fixed paraffin-embedded (FFPE) tissues, which are readily available, for evaluation of high-risk HPV infection in oral cancer. For protocol standardization, we used 20 prospectively collected paired FFPE and fresh tissues of histopathologically confirmed oral cancer cases reported in Oral Medicine department of a dental hospital for comparative study. Only short PCRs (~ 200 bp) of DNA isolated using a modified xylene-free method displayed a concordant HPV result. For HPV analysis, we used additional 30 retrospectively collected FFPE tissues. DNA isolated from these specimens showed an overall 23.4% (11/47) HPV positivity with detection of HPV18. Comparison of HPV positivity from dental hospital FFPE specimens with overall HPV positivity of freshly collected oral cancer specimens (n = 55) from three cancer care hospitals of the same region showed notable difference (12.7%; 7/55). Further, cancer hospital specimens showed HPV16 positivity and displayed a characteristic difference in reported sub-sites and patient spectrum. Overall, using a xylene-free FFPE DNA isolation method clubbed with short amplicon PCR, we showed detection of HPV-positive oral cancer in dental hospitals.

Chronic Liver Disease Presenting as Immune Hemolytic Anemia: The Challenges of Diagnosis in the Critically Ill in a Resource-Limited Health Care Setting.

Immune hemolytic anemia is very rarely associated with chronic liver disease. Diagnosis is often complicated in critically ill patients, where an etiological diagnosis can be elusive, especially in routine health care settings. A 48-year-old man presented with jaundice for three months. Ultrasonography showed features of chronic liver disease. Fibroscan showed increased parenchymal stiffness suggesting cirrhosis. Investigations revealed immune hemolytic anemia and thrombocytopenia. A percutaneous liver biopsy was not performed due to worsening thrombocytopenia. Isolated protein C deficiency and portal vein thrombosis were noted in subsequent testing. The patient eventually succumbed to illness. Coagulopathy such as protein C and D-dimer elevation discovered in subsequent rounds of testing may be misleading in rapidly deteriorating patients, emphasizing the need for timely coagulation workup and imaging. Despite comprehensive testing, lack of liver biopsy, as seen herein, may hamper clinical management. Training residents in the skill of transjugular liver biopsy is necessary to manage critical patients at secondary health care facilities.

Filariasis presenting with bicytopenia, progressive splenomegaly and acute renal failure: An unusual case report.

Extra-lymphatic manifestation of filariasis, especially as acute renal failure, is uncommon and may be clinically unsuspected. We document the case of a 60 year old elderly male who presented with bilateral pedal oedema, fatigue and abdominal distension. Investigations revealed severe anaemia, splenomegaly and acute renal failure. Bone marrow aspiration was performed to evaluate the clinical suspicion of malignancy. Out of eight smears examined, microfilaria (Brugia malayi) were identified in two. This presentation was devoid of peripheral eosinophilia. The patient was commenced on a regimen of diethylcarbamazine, on which he made a good recovery. The incidence of extra-lymphatic filariasis is largely unknown and sparsely reported. Such a presentation should be kept in mind by both clinicians and pathologists as it is potentially treatable.

COVID-19 as an independent risk factor for subclinical placental dysfunction.

BACKGROUND: The pandemic of the severe acute respiratory distress syndrome-associated Coronavirus-2 (SARS-CoV-2) has affected millions around the world. In pregnancy the dangers to the mother and fetus are still being explored. SARS-CoV2 can potentially compromise maternal and neonatal outcomes and this may be dependent on the pregnancy stage during which the infection occurs. OBJECTIVE: The present study was done to find the histopathological alterations in the placenta of SARS-CoV-2 positive pregnancies with either no symptoms or mild coronavirus disease (COVID)-19 related symptoms and its association with neonatal outcomes. STUDY DESIGN: This was a prospective analytical study. Twenty seven asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women with a singleton pregnancy delivered between 1st July 2020 and 15th September 2020, were included as cases. An equal number of SARS-CoV-2 negative singleton pregnancies matched for maternal and gestational age during the same period were included as controls. After delivery the histopathological examination of the placenta of these women was done and the findings recorded on a predesigned proforma based on the Amsterdam consensus criteria for evidence of maternal and fetal vascular malperfusion changes. RESULTS: The baseline characteristics were comparable between the cases and controls. The following features of maternal vascular malperfusion (MVM) were significantly higher in the placentae of COVID-19 positive pregnancies: retroplacental hematomas (RPH), accelerated villous maturation (AVM), distal villous hyperplasia (DVH), atherosis, fibrinoid necrosis, mural hypertrophy of membrane arterioles (MHMA), vessel ectasia and persistence of intramural endovascular trophoblast (PIEVT). Fetal vascular malperfusion (FVM) significantly associated with the positive pregnancies were chorioangiosis, thrombosis of the fetal chorionic plate (TFCP), intramural fibrin deposition (IMFD) and vascular ectasia. Additionally, perivillous fibrin deposition was also significantly higher in the placentae of cases. The percentage of spontaneously delivered women was comparable in the two groups. The sex and weight of the newborn and the number of live births were comparable between the two groups. CONCLUSIONS: Asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women, with otherwise uncomplicated pregnancies, show evidence of placental injury at a microscopic level. Similar findings have been demonstrated in other studies too. This placental injury apparently does not lead to poor pregnancy outcomes. The extent of this injury in symptomatic cases of COVID-19 pregnancies and its consequences on the outcomes need to be analysed.

The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.

Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene. At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing. The isoforms of versican are expressed and accumulate in various tissues during development and disease, where they contribute to ECM structure, cell growth and migration, and immune regulation, among their many functions. While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein. In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway. We further show that N-linked glycosylation is required for efficient secretion and solubility of the protein. By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type. Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion. Once secreted, the V3 protein associates with hyaluronan along the cell surface and within the surrounding ECM. These results establish critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells and establishes a role for V3 in the organization of hyaluronan.

Long-Term Follow-Up of Intratympanic Methylprednisolone Versus Gentamicin in Patients With Unilateral Menière's Disease.

OBJECTIVES: To determine whether long term (>48 months) symptomatic vertigo control is sustained in patients with Menière's disease from a previous comparative trial of intratympanic methylprednisolone versus gentamicin, and if the two treatments remain nonsignificantly different at long-term follow-up. STUDY DESIGN: Mail survey recording vertigo frequency in the previous one and six months, further intratympanic treatment received, and validated symptom questionnaires. SETTING: Outpatient hospital clinic setting. PATIENTS: Adult patients with definite unilateral refractory Menière's disease, who previously received intratympanic treatment in a comparative trial. INTERVENTION: A survey of trial participants who received intratympanic gentamicin (40 mg/mL) or methylprednisolone (62.5 mg/mL). OUTCOME MEASURES: Primary: number of vertigo attacks in the 6 months prior to receiving this survey compared with the 6 months before the first trial injection. Secondary number of vertigo attacks over the previous 1 month; validated symptom questionnaire scores of tinnitus, dizziness, vertigo, aural fullness, and functional disability. RESULTS: Forty six of the 60 original trial patients (77%) completed the survey, 24 from the gentamicin and 22 from the methylprednisolone group. Average follow-up was 70.8 months (standard deviation 17.0) from the first treatment injection. Vertigo attacks in the 6 months prior to receiving the current survey reduced by 95% compared to baseline in both drug groups (intention-to-treat analysis, both p < 0.001). No significant difference between drugs was found for the primary and secondary outcomes. Eight participants (methylprednisolone = 5 and gentamicin = 3) required further injections for relapse after completing the original trial. CONCLUSION: Intratympanic methylprednisolone treatment provides effective long-lasting relief of vertigo, without the known inner-ear toxicity associated with gentamicin. There are no significant differences between the two treatments at long term follow-up.

Does Hypoxia-Inducible Factor -1 α (HIF-1α) C1772T polymorphism predict short-term prognosis in patients with oral squamous cell carcinoma (OSCC)?

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a cancer of the oral cavity that is a major health problem in India. There is an urgent need to identify biomarkers that have prognostic significance. We studied HIF-1α levels as well as single-nucleotide polymorphism of HIF-1α gene in cancer and healthy controls. METHODS: Fifty newly diagnosed OSCC patients and 50 age and sex-matched healthy control were included in the study. Serum concentrations of HIF-1α were measured by sandwich ELISA; whereas HIF-1α gene polymorphism study was performed using restriction enzyme digestion by HpH I. RESULTS: The major genotype observed was CC genotype in both control (84%) and patients (86%) followed by CT genotype (control 16%, cases 14%). CT genotype led to more aggressive tumors. On subgroup analysis based on prognosis, the median overall survival of patients who were treatment responders was 488 days (16.2 months) and that of the patients with progressive disease was 365 days (12.1 months). The patients who expired during the study observation period had median survival of 330 days (11 months). CONCLUSION: Our study showed that CT genotype for C1772T polymorphism of HIF-1α predisposes to aggressive tumor phenotype in patients with OSCC. Moreover, patients with CT genotype had poor survival rate as compared to CC genotype. A cut-off value of 460 pg/mL of HIF-1α can help to segregate patients with OSCC from healthy controls.

Expression of breast cancer type 1 and its relation with expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2/neu in breast carcinoma on trucut biopsy specimens.

OBJECTIVE: (1) The objective is to study the immunohistochemical expression of Breast cancer type 1 (BRCA1) in breast carcinoma on trucut biopsy specimens and (2) To relate its expression with that of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER-2)/neu and the clinicopathological parameters. SETTINGS AND DESIGN: A cross-sectional hospital-based study was performed in Lady Hardinge Medical College and Shrimati Sucheta Kriplani Hospital, New Delhi, with collaboration of the Departments of Pathology and Surgery from the period of November 2008 to March 2010. MATERIALS AND METHODS: The study group included 54 cytologically proven cases of breast carcinoma. The immunohistochemical expression of BRCA1 was studied and related with expression of ER, PR, and HER-2/neu on their trucut biopsies. RESULTS: The altered expression of BRCA1 (i.e., reduced or absent expression) was seen in 44.4% cases of breast carcinoma while 55.6% had positive expression. About 83% of breast carcinomas with altered BRCA1 expression were larger than 3 cm in size. The breast carcinomas showing altered expression were found to be mostly high grade (63.6%). This was statistically significant. The ER and PR negativity were seen in 62.5% and 79.2% breast carcinomas with altered BRCA1 expression, respectively. The score 3 positivity of HER-2/neu was more common among carcinomas with altered BRCA1 expression (21% vs. 16.7%). The triple negativity was found in 41.7% breast carcinomas having altered BRCA1 expression. This was statistically significant. CONCLUSION: The combination of immunohistochemical expression of BRCA1, ER, PR, and HER-2/neu and clinicopathological details may be helpful in predicting the individuals more likely to carry BRCA1 mutations and thus selecting the candidate and family members for genetic screening for BRCA1 mutations.

Masson's Tumor Masquerading as a Papillary Adenocarcinoma on Fine Needle Aspiration Cytology: A Case Report.

Intravascular papillary endothelial hyperplasia, previously known as Masson's tumor, is a relatively uncommon reactive endothelial proliferation that occurs most commonly in the vessels of the head, neck, and extremities. We report a case of intravascular papillary endothelial hyperplasia in the neck in a 40-year-old female that was misdiagnosed as papillary adenocarcinoma on fine needle aspiration. The cytologic picture of intravascular papillary endothelial hyperplasia is diverse, making a pinpoint diagnosis of this entity difficult on fine needle aspiration.

Characterization of key transcription factors as molecular signatures of HPV-positive and HPV-negative oral cancers.

Prior studies established constitutively active AP-1, NF-κB, and STAT3 signaling in oral cancer. Differential expression/activation of specific members of these transcription factors has been documented in HPV-positive oral lesions that respond better to therapy. We performed a comprehensive analysis of differentially expressed, transcriptionally active members of these pivotal signaling mediators to develop specific signatures of HPV-positive and HPV-negative oral lesions by immunohistochemical method that is applicable in low-resource settings. We examined a total of 31 prospective and 30 formalin-fixed, paraffin-embedded tissues from treatment-naïve, histopathologically and clinically confirmed cases diagnosed as oral or oropharyngeal squamous cell carcinoma (OSCC/OPSCC). Following determination of their HPV status by GP5 + /GP6 +  PCR, the sequential sections of the tissues were evaluated for expression of JunB, JunD, c-Fos, p50, p65, STAT3, and pSTAT3(Y705), along with two key regulatory proteins pEGFR and p16 by IHC. Independent analysis of JunB and p65 showed direct correlation with HPV positivity, whereas STAT3 and pSTAT3 were inversely correlated. A combined analysis of transcription factors revealed a more restrictive combination, characterized by the presence of AP-1 and NF-κB lacking involvement of STAT3 that strongly correlated with HPV-positive tumors. Presence of STAT3/pSTAT3 with NF-κB irrespective of the presence or absence of AP-1 members was present in HPV-negative lesions. Expression of pSTAT3 strongly correlated with all the AP-1/NF-κB members (except JunD), its upstream activator pEGFRY1092 , and HPV infection-related negative regulator p16. Overall, we show a simple combination of AP-1, NF-κB, and STAT3 members' expression that may serve as molecular signature of HPV-positive lesions or more broadly the tumors that show better prognosis.