Asis Kumar Karak

Are childhood and adult medulloblastomas different? A comparative study of clinicopathological features, proliferation index and apoptotic index.

Childhood medulloblastomas have been suspected to be biologically different from adult tumors, though comparative studies are sparse in the literature. The present study aims to establish any differences or nexus in the biological characteristics between childhood and adult medulloblastomas. A total of 181 medulloblastomas were studied with respect to clinical and histological characteristics, MIB-1 labeling index (MIB-1 LI), apoptotic index (AI), ratio of apoptotic to LI, p53 and Bcl-2 protein expressions. Two-thirds (112) of the 181 medulloblastomas occurred in children (≤15 years) and 69 in adults (>15 years). Childhood tumors were more commonly of classical histology and midline location while the desmoplastic variant and lateral location occurred more frequently in adults. Adult medulloblastomas were biologically less aggressive, having lower growth rate parameters (mean MIB-1 LI 19.1 ± 15.7; AI 3.73 ± 2.71 and AI : LI 0.207 ± 0.162) as compared to childhood tumors (mean MIB-1 LI 28.3 ± 20.4; AI 2.86 ± 2.14 and AI : LI 0.108 ± 0.111). p53 and Bcl-2 protein expressions were infrequent in all groups of tumors. No difference was noted in any of the parameters when classical and desmoplastic medulloblastomas were compared as a whole. But when compared between the age groups, an interesting observation (hitherto unreported in English literature) was that both classical and desmoplastic variants of childhood medulloblastomas had higher LI, lower AI and lower AI : LI ratio than their counterparts in adults, indicating that differences in growth rates cannot be attributed to differences in the frequency of occurrence of the histological variants in the two age groups. Thus, this study conclusively shows that there is a biological difference between childhood and adult medulloblastomas which is independent of standard histology and appeared to be associated more with age-related factors. This also warrants less-aggressive therapy for adult medulloblastoma.

A study of proliferative markers in central neurocytoma

Summary To gain a better insight into the biological behavior of central neurocytomas, various proliferative indices were studied in these tumors and correlated with the histological features as well as the clinical outcome. Twenty cases of neurocytoma were selected over a 16 year period (1980–1995), which accounted for 0.28% of all intracranial tumors reported at this centre. Treatment consisted of surgical resection (total 14, subtotal six) followed by radiotherapy. Except for five patients who died of surgical complications, the remaining 15 were all alive and well during the follow‐up period, varying from six months to 72 months (average 32 months). Thirteen tumors showed benign histological characteristics (Group I) while seven showed mitoses + necrosis (Group II). The proliferative index was assessed in formalin‐fixed paraffin‐embedded tissue of 17 cases using the silver nucleolar organiser region (AgNOR) technique and immunohistochemical staining for proliferating cell nuclear antigen (PCNA‐PC10 antibody) and Ki‐67 antigen (MIB‐1 monoclonal antibody). The AgNOR counts ranged from 1.2 to 2.6 (mean 1.9±0.4), PCNA labeling index (LI) from 0.1 to 5.5 (mean 2.5±1.8) and MIB‐1 LI from 0.1 to 3 (mean 0.8±0.02). There was no significant difference in any of these parameter values between histological Groups I and II, except that MIB‐1 LI tended to be higher in Group II tumors. Further, there was no significant correlation between these proliferative indices and the mitotic rate of the tumors as well as the survival of the patients. A longer follow‐up will be required to determine the relationship between proliferative markers and outcome as well as to bring out any heterogeneity in their biological behavior. Since these are relatively rare tumors, multicentric pooling of data will be required to reach a definitive consensus regarding their biological aggressiveness and consequentially, the use of radiotherapy in their treatment. The present report is a contribution in this direction.Abbreviations: AgNOR, silver nucleolar organiser region; GFAP, glial fibrillary acidic protein; LI, labeling index; NSE, neuron‐specific enolase; PCNA, proliferating cell nuclear antigen.

Residual goitre in the postiodization phase: iodine status, thiocyanate exposure and autoimmunity

objective  This study was done to assess goitre prevalence, thyroid functional status and cause of residual goitre among school children in the postsalt iodization phase in India.

Clinicopathological features, MIB-1 labeling index and apoptotic index in recurrent astrocytic tumors

This is a study of 64 cases of recurrent astrocytic tumors of all four WHO grades wherein a comparative evaluation of initial vs. recurrent tumor was done with respect to histological grading, MIB-1 labeling index (LI) and apoptotic index (AI). The aim was to identify factor/s that could influence interval to recurrence and/or malignant progression. Recurrence was noted in all grades and upon recurrence, 93.3% of grade II (low grade diffuse) astrocytomas and 63.6% of grade III anaplastic astrocytomas underwent malignant progression. However, none of the Grade I tumors showed evidence of malignant progression. Though interval to recurrence varied considerably, there was a correlation with histological grade of the initial tumor in that grade I and II tumors had a significantly longer mean interval to recurrence (43 months and 54.8 months respectively) as compared to grade III and IV (glioblastoma multiforme) tumors (17.6 and 12.8 months respectively). The interval to recurrence was also longer for grade II and III tumors which showed progression on recurrence (55.3 months for Grade II → Grade III; 54 months for Grade II → Grade IV and 20.6 months for Grade III → IV) as compared to tumors which recurred to the same grade (12.5 months for Grade III → Grade III and 12.8 months for Grade IV→ Grade IV). A statistically significant inverse correlation of MIB-1 LI with interval to recurrence was noted. Higher the MIB-1 LI, shorter was the interval to recurrence. Further a cut off MIB-1 LI value of 2.8% could be proposed in predicting recurrence free survival. Interestingly, MIB-1 LI of grade II tumors, which had progressed to grade IV was significantly higher than MIB-1 LI of grade II tumors which had progressed to grade III. Thus, this study establishes the potential role of MIB-1 LI of the initial tumor in determining interval to recurrence. However, apoptotic index has no role in predicting either interval to recurrence or malignant progression.

Intraventricular neurocytoma: a clinicopathological study of 20 cases with review of the literature.

The clinicopathological features of 20 cases of central neurocytomas are described. They accounted for 0.28% of all intracranial tumours diagnosed during a 16 year period (1980-1995). Lower mean age of the patients at diagnosis (23.1 years), male preponderance (M:F=1.8:1) and higher incidence of involvement of the right lateral ventricle (10/20 cases) were noted in this series, in contrast to reports from Western literature. Total removal of the tumour was done in 14 cases while the remaining six underwent partial resection. Morphogically, the tumours had a striking resemblance to oligodendrogliomas (11/20 had been earlier diagnosed as oligodendrogliomas) and an interesting finding was the presence of dilated vascular channels in 12/20 tumours. The diagnosis was confirmed in all cases by immunohistochemistry and/or electron microscopy. While 18 cases were histologically benign, two had features of atypical neurocytoma. Five patients died due to postoperative complications. The remaining patients received postoperative radiation and their follow-up revealed that all of them were doing well at 12 to 72 months after surgery. These neoplasms should be suspected in any young patient with radiological evidence of an intraventricular lesion; for their differentiation from gliomas, immunohistochemistry and electron microscopy should be done. This is important because, unlike gliomas, these tumours have a relatively favourable prognosis and their current treatment of choice is complete surgical removal without adjuvant chemo- or radiotherapy. Copyright 1999 Harcourt Publishers Ltd.

Etiology, clinical profile, gender identity and long-term follow up of patients with ambiguous genitalia in India.

There is little information on the profile of children with ambiguous genitalia in India. Presented here is an analysis of patients with ambiguous genitalia registered in a general endocrine clinic during the last 2 decades. Seventy-four patients (age 4 months to 36 years) were registered during this period. Fifty-two were more than 5 years old at the time of registration. Thirty-five were reared as females, 29 as males; nine children (4 months to 1 year old) were brought for sex assignment, and one (with epispadias) was brought for correction of urinary incontinence. Investigations revealed 28 patients with congenital adrenal hyperplasia, 14 dysgenetic male pseudohermaphroditism, ten true hermaphroditism, six partial androgen insensitivity, four castration and one epispadias. There were eight patients with perineal hypospadias with normal Leydig cell reserve (normal LH, FSH and testosterone response to LHRH). Sex of rearing and gender identity were concordant in all except the patients with perineal hypospadias with normal Leydig cell response. These observations support the theory that prenatal androgen exposure masculinizes the brain.

Papillary carcinoma of the thyroid and its variants: A cytohistological correlation

Fine‐needle aspiration cytology (FNAC) is considered highly specific for the diagnosis of papillary carcinoma of the thyroid (PCT). In recent years, several variants of PCT have been described. An attempt was made to gauge the accuracy of classification of variants of PCT on aspirates. Cytology smears from 124 of 150 cases of histologically proven PCT with a prior FNAC were reviewed over a 16‐yr period. A diagnosis of papillary carcinoma on FNAC was made in 93 cases. Further subclassification of these cases was done on cytology and tissue sections independently. The variants of PCT classified on FNAC were classical PCT (PCT‐CL), 76 cases; Hurthle‐cell variant (PCT‐HCV), 3 cases; follicular variant (PCT‐FV), 6 cases; tall‐cell variant (PCT‐TCV), 2 cases; high‐grade variant (PCT‐HG), 2 cases; and 2 cases each which were debatably PCT‐CL/PCT‐FV and PCT‐CL/PCT‐HG. Cytology typing was accurate in 65 of the 72 classical variants, while only 7 of the 22 follicular variants were correctly identified on cytology. Two of the 3 high‐grade papillary carcinomas (PCT‐HG) were identified on FNAC, and the solitary case of tall‐cell variant could readily be classified on cytology. In conclusion, identification of the various variants of PCT is possible, though difficulty is encountered in correctly categorizing the follicular variant, which is often mistaken for a follicular neoplasm. Also, identification of the solid variant and the papillary carcinoma with nodular fasciitis‐like stroma was a problem on cytology. Another interesting observation in our series is that an admixture of various cell types was seen in the smears and corroborated on histology to be present in focal areas. Diagn. Cytopathol. 2001;24:167–173.

Imaging in intersex disorders

BACKGROUND Evaluation of the gonads and internal genital structures is an essential component for evaluation of patients presenting with ambiguous genitalia. Ultrasonography (US) and magnetic resonance imaging (MRI) are the two preferred modalities. OBJECTIVE To compare US and MRI in patients with intersex for localization of gonads and internal genitalia. PATIENTS AND METHODS Ten patients with proven intersex disorders were included in the study. Findings from US and MRI were corroborated by those from surgery/laparoscopy. RESULTS For evaluation of the gonads, MRI was found to be marginally more sensitive than US. For internal genital structures, both modalities were found to be equally sensitive and specific with no false positive results. CONCLUSION US still remains the modality of choice for screening patients with intersex disorders. MRI is helpful in cases with equivocal US findings.

Fine‐needle aspiration cytology in a case of isolated involvement of thyroid with Langerhans cell histiocytosis

We present an unusual case of isolated thyroid involvement with Langerhans cell histiocytosis (LCH), diagnosed presumptively by fine‐needle aspiration (FNA) cytology and subsequently confirmed by immunohistochemistry in a 13‐yr‐old boy. The cytologic findings include high cellularity in a hemorrhagic background, the presence of characteristic mononucleated and multinucleated Langerhans cells with prominent nuclear grooves, and abundant foamy cytoplasm in a background of mixed eosinophilic and lymphocytic infiltrate, along with the presence of few focal aggregates of benign thyroid follicular cells. Further diagnostic confirmation was obtained by positive S‐100 protein immunohistochemistry of the Langerhans histiocytes on paraffin‐embedded sections of open thyroid biopsy of the prominently enlarged left lobe. We present the complete clinicopathologic features of this case, along with ultrasound, computerized axial tomographic, and technetium‐99 scan findings. We also discuss possible differential diagnostic consideration in light of a review of the literature and the role of FNA cytologic diagnosis in such a rare yet cytomorphologically characteristic case. Diagn. Cytopathol. 1998;19:33–37.

Immunological subtypes of acute lymphoblastic leukemia in North India

Pretreatment immunologic marker analysis in 152 adult and childhood patients of ALL and ALL/lymphoma employing multiple monoclonal antibodies and hetero-antisera revealed three major subgroups, i.e. T-ALL (37.7%), N-ALL (33.1%) and C-ALL (21.5%). The early age peak was absent, males predominated in all the subgroups and T-ALL had increased incidence of thymic mass. Leucocyte counts of 50,000 X 10(6)/l were equally frequent in the three groups. T-ALL showed marked heterogeneity by showing a variety of markers such as T-helper/inducer, T-suppressor/cytotoxic, p-24, Ia and CALLA. These results show a high prevalence of unfavourable prognostic factors in ALL in our geographic region which might be related to socioeconomic and/or environmental factors.