Indian childhood cirrhosis (ICC) & ICC-like diseases: the changing scenario of facts versus notions.

Indian childhood cirrhosis (ICC), a disease considered to have been endemic in and unique to India has now been documented in children of non-Indian origin from other countries. More recently available findings from a large multicentre study sponsored by the Indian Council of Medical Research (ICMR) have dispelled some of the generally accepted notions and have established several new facts on different aspects of the disease. All relevant reports on ICC and ICC-like diseases, till date, were reviewed to obtain a proper perspective on the current state of our understanding on this non-Wilsonian copper overload liver disease. A primary role of exogenous copper in causing the disease was earlier debated on the basis of studies in India but investigators abroad studying some sporadic cases and a series of endemic ICC-like diseases supported a hepatotoxic injury by ingested copper in genetically susceptible infants and children in ICC- like disease and in ICC. Epidemiologic and morphologic findings in the well controlled ICMR study based on 225 cases of ICC and 426 controls, all confirmed on liver biopsy, have however, convincingly refuted this concept. Additionally, this study revealed that unlike what has been believed earlier, older children more than 3 yr age can get the disease and that in its natural course the hepatic histology can transform between the characteristic one considered diagnostic and some other patterns, any one of which can be the morphologic manifestation at first presentation of the patient. Older children and cases with milder morphologic changes at presentation had longer survival. The overall inference from critical analysis of all available data is that ICC and ICC-like diseases clinically manifest in a child of any age though common in younger ones, and a clinical diagnosis must be made in any child with so-called 'cryptogenic cirrhosis'. Exposure to exogenous copper in food, milk and water should not be a prerequisite for this consideration. A liver biopsy whenever feasible should be mandatory for confirmation with the understanding that the morphologic changes in liver can present a few other patterns besides the characteristic one currently taken to be diagnostic. The ascribed current decline in encountering ICC is likely to be due partly to missing a diagnosis and partly to a true reduction in incidence consequent on time related economic and socio-cultural changes.

Kaposi's sarcoma in a patient with AIDS.

We report a case of a 40 year old HIV infected male, citizen of Somalia who presented with multiple painful, livid reddish brown plaques, papules and nodules on both lower limbs and purplish red nodules on the hard palate. The cutaneous nodular lesions on biopsy showed characteristic features of Kaposi's sarcoma. This case is reported due to paucity of Kaposi's sarcoma in Indian literature.

Sudden death due to cardiac toxoplasmosis.

The recognition of cardiac toxoplasmosis has increased in patients with acquired immunodeficiency syndrome. The functional consequences of toxoplasmosis of heart vary considerably depending on the intensity of inflammatory reaction, the extent of involvement of myocardial muscle fibers by necrosis and intramyocytic presence of tachyzoites of Toxoplasma gondii. This report describes a case of toxoplasma myocarditis that lead to fatal cardiac arrest. To the best of our knowledge, this is the first reported case of cardiac toxoplasmosis in the Indian literature, which has manifested as sudden death.

Meningiomas: report of a hospital-based registry.

This is a hospital-based epidemiologic study of meningiomas. Of 1321 central nervous system tumours, meningiomas constituted 21% of the cases, being the second largest category of a single histologic type after astrocytomas. Of the 267 meningiomas studied, 247 were intra-cranial (92.5%). The age of the patients varied between 6 to 84 years. Histological subclassification is presented and treatment schedules discussed. 261 (98%) meningiomas were histologically benign and 5 were malignant meningiomas (1.9%). A 5-year follow-up was available in most cases, with the help of which it was possible to understand the biological behaviour of various sub-types and the influence of other parameters such as location and treatment schedules. Of note was the fact, that out of 261 patients with benign meningiomas, 11 succumbed in the immediate post-operative period and in 8 of these cases, the tumour was located at the base of the skull.

Penicillium marneffei infection: an AIDS-defining illness.

A 29-year-old HIV seropositive male patient from Manipur presented with fever, cough, weight loss and asymptomatic papules and nodules all over the body. Differential diagnoses of secondary syphilis, histoplasmosis, cryptococcosis and penicilliosis were considered. Histopathological and mycological study of the skin biopsy tissue, and blood culture confirmed the diagnosis of penicilliosis. Although penicilliosis, an AIDS-defining illness, is restricted to Southeast Asia, more and more cases are being recognized in non-endemic countries.

A study of clinical and laboratory features of 14 Indian patients with dysferlinopathy.

AIM: The aim of the study was to analyze the clinical and laboratory characteristics of Indian patients having dysferlinopathy. METHODS AND MATERIAL: Patients with limb girdle muscular dystrophy (LGMD) were prospectively studied. History, examination, and laboratory evaluation, including creatine kinase, electrophysiology, and muscle biopsy with immunocytochemistry, was carried out. RESULTS AND CONCLUSIONS: Fourteen patients (14.58% of patients with LGMD) had dysferlin deficiency. The mean age at onset was 19.9 years. Nine patients had distal presentation and in the remaining 5 patients, it was proximal. Asymmetry of muscle weakness was seen in 6 patients. Three patients experienced initial calf pains with transient hypertrophy. Gastrocnemius and tibialis anterior muscles were almost similarly affected. The brunt of proximal weakness was on iliopsoas, hip adductors, hamstrings, and quadriceps muscles. Upper limbs were mildly affected. Biceps lump was seen in 4 patients. The phenotype was mild and ambulation was maintained in all patients, many years into the illness.

Epstein-Barr virus in nasopharyngeal carcinoma in Indian patients.

Formalin fixed paraffin embedded tissue blocks from 40 cases of nasopharyngeal carcinoma were investigated for the presence of Epstein-Barr virus (EBV). Heminested polymerase chain reaction was employed to amplify U 2 region of EBV DNA coding for EBNA 2 gene. This is the first study of its kind carried out in India. EBV was detected in 28 out of 40 (70%) nasopharyngeal carcinomas. Type A EBV was identified in 20 cases (71.4%), type B in 7 cases (25%) and coinfection in one case (3.5%). Either type A, or type B EBV, was identified in 22 out of 23 cases (95.7%) of undifferentiated nasopharyngeal carcinoma and 6 out of 15 cases (40%) of non keratinized squamous carcinoma. The higher incidence of EBV in non keratinized squamous carcinoma of nasopharynx assumes importance in view of the contrary reports in other studies. 26 cases were from Western India, of which 15 (57.6%) showed presence of type A EBV and 2 (7.6%) type B EBV. From Eastern Indian particularly Assam, 4 our of 5 cases showed positivity for type B EBV and 1 a coinfection. Whereas, from Bihar 3 out of 4 cases showed presence of type A EBV. From Middle East (Arabs) type A EBV was detected in 3 out of 5 cases of nasopharyngeal carcinomas. Geographically, type A EBV was far more prevalent in Western India, while in Eastern India particularly Assam, all five vases were positive for type B EBV. Thus, a significant variation in the type of EBV infection was observed in nasopharyngeal carcinoma in different ethnic populations in India.

Senile systemic amyloidosis--a case report.

An 85 years old female presented with acute pain and weakness in left lower extremity and doppler evidence of femoropopliteal block was made which subsequently proved fatal. Necropsy revealed extensive amyloid deposition in the heart and amyloid angiopathy in rest of the organs.

Squash preparation and frozen section in intraoperative diagnosis of central nervous system tumors.

OBJECTIVE: To investigate the diagnostic accuracy of squash preparation (smears) and frozen section (FS) in the rapid intraoperative diagnosis of central nervous system (CNS) tumors. STUDY DESIGN: One hundred eighty-three CNS tumors were examined over a period of 18 months (January 1995-June 1996). All these were open biopsies, and the smear interpretation was compared with FS findings and paraffin section diagnosis. RESULTS: In 183 tumors, squash preparation was satisfactory in 156 cases (85.2%), and the diagnostic accuracy was 89.7% (140/156). The accuracy of FS diagnosis was 90.4% (141/156). CONCLUSION: The squash smear preparation is a fairly accurate and reliable tool in the rapid intraoperative diagnosis of CNS tumors. The accuracy of this technique is nearly as good as that of FS (P value = .9877). With the advent of stereotactic biopsies, the pathologist may have to depend entirely upon cytologic features for a definitive diagnosis.

Primary central nervous system lymphoma.

A clinicopathological analysis of 18 cases of primary intracranial malignant lymphoma encountered in the period 1980 to 1994 is presented. The total SOL's in this period was 924, the incidence of malignant lymphoma working out to 2%. The patients age ranged from 14 to 72 years with maximum prevalence in the sixth and seventh decade. The male to female ratio was 2:1 and the patients presented with evidence of CNS deficit, change in mental status or raised ICI. 15 cases had a single site of involvement while 3 patients had multicentric lesions. As far as could be determined none of the cases had evidence of immunesuppression and test for HIV carried out in five cases was negative. All the tumors were subjected to light microscopy and the diagnosis was confirmed either by ultrastructural examination or immunohistochemistry. 13 tumors were large cell high grade lymphomas while the rest revealed smaller cells. Eleven patients received post operative radiotherapy and two were given post operative chemotherapy. The outcome of the patients was poor in most cases, fifteen out of eighteen died within two years.

Nuclear decondensation of sperm head and failure at in-vitro fertilization: an ultrastructural study.

The problem of unexplained male infertility was investigated by electron microscopic study of spermatozoa from 51 males. The subjects were subdivided as follows: group A (n = 25) normal fertile males (controls), group B (n = 13) successful in-vitro fertilization (IVF) cases (fertilization rate > 50%), group C (n = 13) failed IVF cases. All subjects included in groups B and C had a 6-12 year history of childlessness and IVF was employed when other methods of assisted reproduction failed. The study of spermatozoa in fertile males (controls) was carried out to establish baseline ultrastructural abnormalities. In all 51 cases, an average of 330 (280-800) sperm heads and 660 (330-1190) sperm tails were studied. Decondensation of nuclear chromatin was observed in 70 +/- 15% (mean +/- SD) of spermatozoa in failed IVF cases, 16 +/- 5% in successful IVF cases and 7 +/- 3% in controls. These results were found to be statistically significant (P > 0.001). The mean value for motility of spermatozoa in all three groups was within accepted limits of normality. It is concluded that decondensation of nuclear chromatin seen by electron microscopy is one of the most important causes of male infertility. It is advocated that electron microscopic examination of semen should be carried out in all cases of long-standing, unexplained male infertility before embarking upon IVF programmes.

Percutaneous renal biopsy using Monopty needle.

Forty six percutaneous renal biopsies (thirty one native and fifteen transplant kidneys) were performed using the Monopty needle, compared with equal number of biopsies performed using the Travenol Tru-cut needle. The core length of samples obtained ranged from 3-16 mm using Monopty and 5-13 mm using Tru-cut. Adequate tissue was obtained in 65.5% and 80.4% of cases with the use of Monopty and Tru-cut respectively. Both the needles gave equal number of reuses. The use of Tru-cut needle was associated with serious complications like gross haematuria requiring blood transfusions and perinephric haematoma in ten cases whereas only two cases developed haematuria when the Monopty needle was used. In view of its greater safety we have switched over to using the Monopty needle for percutaneous renal bipsies.

Glomerular basement membrane abnormalities in infants with heavy proteinuria.

Two Indian male children with infantile-onset heavy proteinuria (with nephrotic syndrome in 1) had thickening of the glomerular basement membrane with splitting and basket-weave appearance of lamina densa on electron microscopic evaluation of kidney tissue (like Alport's syndrome), with normal light microscopic findings and negative immunofluorescence. The proteinuria was non-familial and was not associated with microhaematuria in patient 1; transient microhaematuria, perhaps associated with urinary tract infection, was noted in patient 2. There was no neurosensory deafness in the patients or their parents. The nephrotic syndrome remitted totally in one patient over a 7-month period. The proteinuria, as well as the renal disease, was non-progressive in the second patient over a 27-month period. The significance of these basement membrane abnormalities (classically described in Alport's syndrome) in early-onset nephrotic syndrome/heavy proteinuria that is non-familial and non-progressive needs to be evaluated.

Use of combined myeloperoxidase and immunogold technique in hybrid leukemia: a case report.

A case of hybrid leukemia is presented. A 30-year-old man had two blast cell populations with bone marrow. The majority of the blast cells had B-lymphoid markers on their surfaces and a small number of cells had both lymphoid markers and penoxidase activity on the same cell. Immunoelectron microscopy combined with ultrastructural cytochemistry (MPO reaction) demonstrated the biphenotypic nature of the blast cells.

Peripheral nerve sheath tumours: an ultrastructural study of 30 cases.

This report deals with the ultrastructural observations of 30 peripheral nerve sheath tumours [PNST], which include 25 schwannomas of acoustic nerve, one schwannoma of cauda equina, one neurofibroma from a case of Von Recklinghausen's disease, one pigmented neurofibroma of spinal nerve root and a malignant schwannoma of frontal region. Interdigitating slender cytoplasmic processes covered with a continuous layer of basal lamina constitute the single most important ultrastructural attribute of Schwann cells. Myelin formation was encountered in the cell processes of four out of 25 acoustic schwannomas. In four cases Microtubular arrays identical to that in an axon were seen in Schwann cells. These two observations require further support by additional cases of PNST studies by electron microscopy. The neurofibroma consisted only of Schwann cells and no ultrastructurally identifiable perineurial cells or fibroblasts were detected. The cells in the pigmented neurofibroma revealed submicroscopic features of both Schwann cell and melanocyte, indicating their common ancestry. A unique case of malignant schwannoma arising from frontal meninges is illustrated and it is emphasized that electron microscopy is mandatory for a correct histogenetic diagnosis of malignant tumours which occur at unexpected anatomical sites.

Pleomorphic intimal sarcoma of pulmonary artery. A case report.

A rare case of pleomorphic intimal sarcoma of pulmonary trunk is reported. The patient presented with symptoms of right ventricular out flow tract (RVOT) obstruction. Metastatic deposits were seen in lungs, diaphragm and thyroid. Bronchial mucosal involvement was also seen. The tumour showed multicentric origin and on electron microscopic examination in a particular cell line was seen.

Comparative pathology of canine mammary tumours.

The pathological features of 52 canine mammary tumours were studied and compared with those of human breast neoplasms. In many of the former, the constituent cells were both epithelial and myoepithelial. Cartilaginous and osseous metaplasia of the stromal tissue was striking in a few tumours. Carcinosarcomas were also encountered. On a careful search, virus-like particles were observed in five tumours. The similarities and differences between the human and canine mammary tumours were discussed with a view to assessing the suitability of dog mammary tumour as an animal model for human breast tumours.

Rat renal mesenchymal tumor as an experimental model for human congenital mesoblastic nephroma: II. Comparative pathology.

The morphological features of kidney neoplasms induced by ethylnitrosourea (ENU) with or without prior irradiation were examined with a view to comparing them with human renal tumors of childhood. The rat renal tumors consisted of poorly differentiated, highly mitotic mesenchymal cells frequently attempting to differentiate along fibroblastic and myofibroblastic lineages. Though the host renal tubules were frequently entrapped in these tumors, immature tubules and islands of epithelial cells occasionally were seen to form an integral part of the neoplasms. Rarely, adenomatous areas surrounded by mesenchymal proliferation were observed. None of the tumors had the blastemal component that is the hallmark of nephroblastoma. The rat mesenchymal tumors resembled the human congenital mesoblastic nephroma.