Pediatric Clear Cell Renal Cell Carcinoma with Pelvicalyceal System Invasion and Contiguous Extension Upto Bladder: Novel and Bizarre Tumor Behaviour.

BACKGROUND: Paediatric renal cell carcinoma (RCC) is a rare neoplasm which differs significantly in its clinico-pathological behaviour from the adult variant. The clear cell variant constitutes a relatively small histological subset of this neoplasm. CASE REPORT: We present a very unusual, pathologically proven case of clear cell variety of pediatric RCC which showed invasion into the pelvicalyceal system with contiguous extension up to the urinary bladder. Such a novel manifestation of paediatric RCC has not been described previously in literature. A relevant review of literature is included. CONCLUSIONS: The aggressive biological behaviour of the paediatric RCC in our case and the consequent atypical imaging findings are distinctly unusual. These findings may represent a new aggressive variant of this rare neoplasm. The radiologist and clinician should be aware of these novel manifestations of paediatric clear cell RCC.

Optic nerve involvement in a borderline lepromatous leprosy patient on multidrug therapy.

Amidst the plethora of ocular complications of leprosy, involvement of the posterior segment or optic nerve is extremely rare. The mechanism of optic neuritis in leprosy is poorly understood. A 47 year-old man presented with a single lesion suggestive of mid-borderline (BB) leprosy over left periorbital region; the histology showed borderline lepromatous (BL) leprosy with a BI of 3+. After initial improvement with WHO MDT-MB and prednisolone (40 mg/d) he developed sudden and painless diminished vision in the left eye, about 3 weeks later. His visual acuity was 6/9 in the left and 6/6 in the right eye, and there was left optic disc edema, hyperemia and blurred disc margins. Treatment with prednisolone (60 mg/d) along with WHO MDT-MB continued. A month later he returned with painless diminished vision in the other eye as well. Visual acuity was 6/6 in the right and 6/12 in the left eye, and there was right optic disc edema and left optic disc atrophy. CT of the head and MRI of the brain were normal. Inflammatory edema of the orbital connective tissue or other surrounding structures, or direct infiltration of vasa nervosa with resultant vascular occlusion leading to optic nerve ischemia, seems the most plausible explanation of optic nerve involvement in this case.

Tissue concentration of aldosterone in fetal adrenals of intrauterine death cases.

OBJECTIVES: Fetal adrenals are one of the main organs responsible for maturation and survival. Extant literature is not clear about whether second trimester fetal adrenals are capable of synthesizing secreting aldosterone. METHODS: We have taken 20 adrenals from fetuses of intrauterine death cases. None of the fetuses had any external malformations and obstetric history was unremarkable. The organs were weighed and homogenized. The supernatant was used for aldosterone estimation by ELISA. RESULTS: We consistently detected aldosterone in all the cases including second trimester. However, we did not see any correlation between aldosterone concentration and gestational age. It is striking to note that there are wide variations in the tissue levels of aldosterone across different gestational ages and also same period. CONCLUSIONS: Tissue aldosterone levels in second trimester can be possibly induced by stress preceding intrauterine deaths. It is possible that functional status of adrenal is different in intrauterine death cases as opposed to elective abortions in second trimester.

COVID 19 mortality: Probable role of microbiome to explain disparity.

There is a significant difference between COVID 19 associated mortality between different countries. Generally the number of deaths per million population are higher in the developed countries despite better health care efficiency, drinking water quality and expected healthy life span (HALE) at the time of birth. Developing and underdeveloped countries on the other hand have lower mortality even with higher rural and slum populations along with incidence of diarrhea because of lack of sanitation. We analyzed data from 122 countries out of which 80 were high or upper middle income and 42 were low or low middle income countries. There was statistically significant positive correlation between COVID 19 deaths /million population and water current score, health efficiency, and HALE. Statistically significant negative correlation was observed with % rural population and fraction of diarrhea because of inadequate sanitation for all ages. Moreover analysis of 51 countries showed that there is significant negative correlation between COVID 19 deaths /million population and proportion of total population living in slums. We propose that high microbial exposure particularly gram negative bacteria can possibly induce interferon type I which might have a protective effect against COVID 19 since the countries with less mortality also tend to have lack of sanitation and high incidence of attendant diseases. So, far none of the predictive models have taken into account immune status of populations engendered by environmental microbial exposure or microbiome. There might be a need to look at dynamics of COVID 19 pandemic using immune perspective. The approach can potentially inform better policies including interventions.

Low apoptotic index & bak expression in EBV-associated childhood classical Hodgkin lymphoma.

BACKGROUND & OBJECTIVE: Association of Epstein-Barr virus (EBV) with Hodgkin lymphoma (HL) is particularly high in low-income countries, and resistance to apoptosis might play a role in pathogenesis and survival. Data from previous studies are not consistent, and none is available in children. Thus this study was undertaken on Indian children with classical Hodgkin lymphoma to assess the significance of bcl-2, bak and p53 expression, and apoptotic index in relation with EBV status and treatment outcome with chemotherapy alone. METHODS: Children (age<15 yr) with classical HL (n=143) were included in the study. Bcl-2, bak, p53, Ki67 and latent membrane protein-1 (LMP1) were detected by immunohistochemistry in pre-treatment lymph node biopsies. Apoptotic index was assessed by TdT-dUTP nick-end labelling (TUNEL). RESULTS: Bcl-2, bak, p53 were expressed above positivity threshold in 83.3, 94.0 and 7.1 per cent of the cases respectively. More than 10 per cent of apoptotic tumour cells were seen in 60.4 per cent of the cases. 131 (91.6%) cases were EBV associated. EBV-positive cases had a significantly lower mean bak expression (p=0.001) and a lower apoptotic index, without higher proliferation index. Advanced stage showed a borderline association with bcl-2 expression in >25 per cent of tumour cells and p53 negative tumours. In univariate analysis, p53 positive cases, which were significantly associated with B symptoms, had a poorer overall survival (P=0.03) while low proliferation index was associated with poorer failure-free survival. Neither EBV status nor any of the apoptotic parameters studied showed independent association with survival. INTERPRETATION & CONCLUSION: EBV detection in children with classical Hodgkin lymphoma was associated with significant lower bak expression and with lower spontaneous apoptosis of H-RS cells suggesting that EBV-LMP1 might downregulate bak pro-apoptotic protein. this needs to be substantiated further.

MAPKAPK2 plays a crucial role in the progression of head and neck squamous cell carcinoma by regulating transcript stability.

BACKGROUND: Head and neck squamous-cell carcinoma (HNSCC) ranks sixth among cancers worldwide. Though several molecular mechanisms of tumor initiation and progression of HNSCC are known, others remain unclear. Significance of p38/MAPKAPK2 (Mitogen-activated protein kinase-activated protein kinase-2) pathway in cell stress and inflammation is well established and its role in tumor development is being widely studied. METHODS: We have elucidated the role of MAPKAPK2 (MK2) in HNSCC pathogenesis using clinical tissue samples, MK2-knockdown (MK2KD) cells and heterotropic xenograft mice model. RESULTS: In patient-derived tissue samples, we observed that MK2 is reproducibly overexpressed. Increased stability of cyclin-dependent kinase inhibitor 1B (p27), mitogen-activated protein kinase phosphatase-1 (MKP-1) transcripts and decreased half-life of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) transcripts in MK2KD cells suggests that MK2 regulates their transcript stability. In vivo xenograft experiments established that knockdown of MK2 attenuates course of tumor progression in immunocompromised mice. CONCLUSION: Altogether, MK2 is responsible for regulating the transcript stability and is functionally important to modulate HNSCC pathogenesis.

Enterobius vermicularis infestation leading to Meckel's diverticulitis in an adolescent boy: An extremely rare presentation.

Enterobius vermicularis is an intestinal nematode commonly affecting children worldwide. Its transmission is by feco-oral route. Meckel's diverticulitis due to E. vermicularis infestation is an extremely rare presentation. An 11-year-old boy presented with acute abdomen. During surgery inflamed Meckel's diverticulum (M.D) was seen. Histopathology examination of specimen revealed E. vermicularis. Till date, only one case of E. vermicularis infestation of M.D is reported around five decades ago. This histopathological confirmation is extremely important as the required treatment (Mebendazole) of the infected case along with household contacts can prevent the spread of infection and may avoid surgery in known contacts.

Chondrosarcoma third metacarpal: Diagnosis and management options.

Chondrosarcoma is a rare malignant tumor of cartilage commonly arising in the pelvis, proximal femur, and humerus, but quite uncommon in the small bones of the hand. Although limited surgical procedures such as curettage are mentioned as a management option in low-grade chondrosarcomas, they tend to have a high rate of recurrences. Hence, wide excision is recommended as a treatment option even in low-grade chondrosarcomas of the hand.

Cerebral blastomycosis: a case report.

Blastomycosis is a chronic systemic fungal infection characteristically affecting the skin and lungs. Involvement of the central nervous system (CNS) is unusual, with cases generally presenting with meningitis, and rarely as intracranial mass lesion and solitary or multiple abscesses. Only two cases of intracranial extra-axial blastomycosis have been reported from India, and we report the third case, which presented as meningioma in a 23-year old female.

Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians.

AIM: To evaluate the clinical and biochemical profile of patients with non alcoholic fatty liver disease (NAFLD) and to assess their histological severity at presentation. METHODS: Consecutive patients presenting to the liver clinic of All India Institute of Medical Sciences (AIIMS) with raised transaminases to at least 1.5 times upper limit of normal, and histologically confirmed non-alcoholic fatty liver disease were included. Patients who had significant alcohol intake or positive markers of other liver diseases or who were taking drugs known to produce fatty liver were excluded. The clinical, biochemical and histological profile of this group was studied. RESULTS: Fifty-one patients with NAFLD formed the study population. Their median age and BMI were 34(17-58) years and 26.7(21.3-32.5) kg/m(2) respectively and 46 (90.1%) were males. The majority of the patients had mild inflammation, either grade 1 [32 (63%)] or grade 2 [16 (31%)] and only 3 (6%) patients had severe (grade 3) inflammation. Twenty-three (45%), 19 (37%), 8(16%) and 1(2%) patient had stage 0, 1, 2 and 3 fibrosis respectively on index biopsy and none had cirrhosis. On univariate analysis, triglyceride levels more than 150 mg % (OR = 7.1; 95% CI: 1.6-31.5, P = 0.002) and AST/ALT ratio>1 (OR = 14.3; 95% CI: 1.4-678.5, P = 0.008) were associated with high grades of inflammation and none was associated with advanced fibrosis. On multivariate logistic regression analysis, hypertriglyceridemia >150 mg% was the only factor independently associated with presence of high grade of inflammation (OR = 1.6; 95% CI: 1.3-22.7, P = 0.02), while none was associated with advanced fibrosis. Triglyceride levels correlated positively with inflammatory grade (r = 0.412; P = 0.003). CONCLUSION: NAFLD in North Indian patients is a disease of young over-weight males, most of whom are insulin resistant and they tend to have a mild histological disease at presentation.

Cholecystitis Associated with Heterotopic Pancreas, Pseudopyloric Metaplasia, and Adenomyomatous Hyperplasia: A Rare Combination.

Heterotopic pancreatic tissue in the gall bladder is an uncommon incidental finding in most cases. We hereby describe the case of a 45-year-old woman who presented with symptoms of acalculous cholecystitis. Pathological examination detected heterotopic pancreatic tissue, pseudopyloric metaplasia, and adenomyomatous hyperplasia in the gall bladder. This is a rare combination of three entities which is being reported for the first time. This case emphasizes that heterotopic pancreas might be the causative factor for cholecystitis.

Vitamin E-based therapy is effective in ameliorating transaminasemia in nonalcoholic fatty liver disease.

BACKGROUND: Comparative trials of ursodeoxycholic acid (UDCA), vitamin E and weight management programs among patients with nonalcoholic fatty liver disease (NAFLD) are lacking. AIM: To find an effective single agent or combination of agents for management of NAFLD. METHODS: In this retrospective study, consecutive patient with histologically confirmed NAFLD with raised ALT were included. The patients received either weight management (exercise and therapeutic lifestyle changes [TLC] diet with a target to reduce body weight 10% in 6 months) (group I) ; weight management + UDCA (300 mg BID) (group II); or weight management + UDCA + vitamin E (400 mg OD) (group III). Outcome measure was normalization of ALT. RESULTS: 42 patients (18, 12 and 12 in groups I, II and III, respectively) were included between 1996 and 2004. All patients in group III normalized their ALT levels, which was significantly higher than numbers in group I (8/18) and group II (5/12); (p=0.003). Post treatment ALT was significantly lower in group III (28.6 [9.3]) as compared to group I (59.3 [32.2]) and group II (49.0[31.8]); (p=0.01). Type of therapy received was the only factor predictive of ALT normalization. CONCLUSION: Combination regimen containing vitamin E appears to be effective in normalizing ALT among NAFLD patients.

Osseous metaplasia in leiomyoma: A first in a uterine leiomyoma.

Being one of the commonest tumors of the female genital tract during the reproductive years, the leiomyoma uteri expectedly demonstrates a wide spectrum of histological variations. However, heterologous tissue differentiation is a rare finding and frank bone formation is even rarer. The factors that lead to heterologous tissue formation in a leiomyoma are subject to speculation. This is a rare case report and possibly the first, on the formation of pure mature bone in a uterine leiomyoma.

Synchronous Lipoma arborescens of bilateral wrist: An extremely rare manifestation and a new perspective on etiopathogenesis.

Lipoma arborescens is a rare lesion wherein abnormal proliferation of adipocytes in the subsynovial region is seen. Whether it is neoplastic or not is still not entirely clear. Usually, Lipoma arborescens is seen unilaterally around knee joint but it can also be seen around tendon sheaths or bursa in adults. Multiple lesions are also reported. Involvement of wrist is extremely rare. We are presenting a case with bilateral wrist involvement by Lipoma arborescens which to the best of our knowledge is first one in English literature. There are a host of co-morbid/associated conditions reported with Lipoma arborescens out of which chronic irritation and inflammation appears to be most significant. We are proposing a novel perspective on etiopathogenesis of Lipoma arborescens based on extant understanding of cellular differentiation and information gleaned from fetal autopsies. The new perspective also explains the predilection for knee joint.

Mucinous tubular and spindle cell carcinoma of kidney: A case report of an unusual tumor.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare and unusual variant of renal cell carcinoma (RCC). It is important to differentiate this from the other variants particularly papillary RCC since MTSCC is generally low-grade, has low malignant potential and favorable prognosis. We are reporting a 40-year-old female presenting with right flank pain and well-circumscribed renal mass confined to the lower pole. Tumor consisted of tubules and cords separated by pale mucinous material in some areas, whereas other areas showed dense cellularity without significant mucin. The tumor cells were cuboidal or spindle and did not show significant atypical features. The patient underwent nephrectomy and is asymptomatic clinically and radiologically after 2 years.

Renal cell carcinoma, unclassified with unique features.

Renal cell carcinoma, unclassified constitute about 3-4% of all renal carcinomas. It essentially is a tumor where more than morphological variants or subtypes are seen in a single tumor. Usually there is a mixture of 2-3 different types. However, in this particular case there were at least 5 different types of morphological patterns in a single tumor including areas of so-called rhabdoid differentiation. The patient underwent nephrectomy and has been asymptomatic for the last 3.5. years. To the best of our knowledge, this is the first case of its own kind in the published literature.

Lymphangiomatosis: Two cases with unique presentations, salience of nomenclature, and diagnosis.

We are presenting two unique cases of lymphangiomatosis without visceral and bony involvement and critically discussing the nomenclature used in the extant literature. The first case was a 12-year-old boy with ill-defined mass on the right cheek extending into the ipsilateral orbit leading to conjunctival lesion. The second case was of a 14-week-old infant showing diffuse swelling on nape of the neck. In addition there were raised patches on dorsal aspects of bilateral hands and feet. The biopsies from all the lesions showed similar histopathological features consistent with lymphangiomatosis. We propose that the term lymphangiomatosis should be used only in cases with histological features of lymphangiomatosis. The term should not be used in cases of multiple lymphangiomas. We conclude that the lesions clinically diagnosed as lymphangioma may turn out to be lymphangiomatosis. Extensive lymphangiomatosis without visceral or bony involvement may lead to intrauterine death.

Angioleiomyoma uterus in an adolescent girl: a highly unusual presentation.

BACKGROUND: Uterine angioleiomyoma is a very rare gynecologic tumor; only a few such cases have been reported to date and we have found no such tumor reported in an adolescent girl. CASE: We report the case of a uterine angioleiomyoma in an adolescent girl. It presented as a huge abdomino-pelvic mass. The girl had severe menorrhagia and severe anemia. Intra-operatively no distinct planes were found between myoma and myometrium. Due to severe hemorrhage, she underwent sub-total abdominal hysterectomy. SUMMARY AND CONCLUSION: Uterine angioleiomyoma is an extremely rare tumor since only 16 such cases have been reported to date. Its appearance in an adolescent girl seems to be the first case of its kind. So it is being reported not only to familiarize the managing physicians with the possibility of such a tumor and its variable presentation, but also to highlight the need for inclusion of this tumor in WHO classification of tumors of the female genital tract.

Chondrocutaneous branchial remnants or cartilaginous choristoma: terminology, biological behavior and salience of bilateral cervical lesions.

OBJECTIVE: To present and critically examine the spectrum of chondrocutaneous branchial remnants or accessory pinna, including rare case of bilateral cervical lesions, and to explain the basis of the biological behavior. MATERIAL AND METHOD: Five cases of pediatric chondrocutaneous branchial remnants or accessory pinna were included. The ratios of the longest dimensions of the external ear to that of the accessory tragus/chondrocutaneous branchial remnants were calculated. RESULTS: The size and rate of growth of chondrocutaneous branchial remnants or accessory pinna were found to be inversely proportional to the distance between the lesions and the normal pinna. CONCLUSION: The current literature and norms of terminology dictate that two different terminologies for lesions that are essentially histologically identical should be avoided. Chondrocutaneous branchial remnants, accessory pinna/tragus and chondroid/ cartilaginous choristomas are identical lesions with similar pathogeneses and should be referred to as choristomas.