Ritu Lakhtakia

Hepatocellular carcinoma in a hepatitis B ‘x’ transgenic mouse model: A sequential pathological evaluation

Background: The introduction of transgenic technology has made it possible to study the steps of carcinogenesis and directly establish the link between viral subgenomic fragments and specific types of cancer. Research directed at hepatitis B virus (HBV)‐related carcinogenesis has benefited from this technology. We present a detailed pathological evaluation of the sequential steps of hepatocarcinogenesis in a hepatitis B ‘x’ (HBx) transgenic mouse model. In this model, the transgene incorporates the region encoding amino acids 58–154 of the HBV X protein and the murine c‐myc gene. This model demonstrated changes in the liver from birth with foci of multicentric dysplasia evolving into nodules and overt hepatocellular carcinoma between 20 and 28 weeks.

Ependymoma with extensive lipidization mimicking adipose tissue : A report of five cases

Lipomatous ependymoma is a recently described entity and only 3 cases of this variant have been reported in the literature. We report 5 cases of this rare variant of ependymoma. Patients’ age ranged from 4 years to 45 years and, interestingly, all of them were males. Two tumors were supratentorial in location, 2 in the fourth ventricle and 1 was intramedullary. Microscopically all of them showed the classical histology of ependymoma along with lipomatous differentiation. The lipomatous component was composed of cells with a large clear vacuole pushing the nucleus to the periphery and giving a signet ring cell appearance. This component demonstrated positivity for GFAP and S-100 protein thereby confirming its glial lineage. Three of the 5 tumors were high grade (WHO-grade III), had a high MIB-1 labelling index (MIB-1 LI) and showed recurrence on follow-up. However, 2 were low grade (WHO grade II) and patients are free of disease till the last follow up.

Chronic subdural haematoma and the enigmatic eosinophil

Summary. The membranes from 50 cases of chronic subdural haematomas were examined histologically and correlated with the duration of the lesion. Cases were divided into three groups based on duration from time of trauma and/or onset of clinical symptoms to date of surgery – Group I: 1 to 30 days, Group II: 31 to 90 days and Group III: >90 days. Infiltration with eosinophils was observed in the vascularised and hyalinised granulation tissue of the subdural membrane in 30 of the 50 cases (60%). There was a trend to correlation both of the frequency and the extent of eosinophilic infiltration with duration of haematoma. Thus, eosinophils were encountered in about half the cases with duration up to 3 months which increased to 80% in cases with duration more than 3 months. The extent of eosinophilic infiltration (mild, moderate or severe) also appeared to correlate with duration of haematoma in that mild infiltration was more common in Group I cases while moderate to severe infiltration were more frequently observed in Group II and III cases. No correlation was observed of the eosinophilic infiltrate with age and sex of the patients or with presence of other cellular inflammatory components of the membrane. Interestingly, a finding hitherto unreported in English literature was the demonstration of mast cells in 7 of 16 membranes (44%) which had been stained using toluidine blue. It is possible that the eosinophils appear at this unusual site due to chemotactic stimulus abetted by these mast cells as well as lymphocytes and haemosiderin pigment. The eosinophils may have an important role in the repair and healing process of these membranes.

Villoglandular papillary adenocarcinoma of the cervix: Case report

The incidence of cervical adenocarcinoma is on the rise over the last several decades. It generally carries a worse prognosis than squamous carcinoma. Villoglandular papillary adenocarcinoma (VGA) of the cervix has been identified as a distinct subset of cervical adenocarcinoma that occurs in young women and supposedly carries an excellent prognosis. We report a case of adenocarcinoma of the cervix in a young woman that had classical histological features of VGA but at operation showed presence of tumor cells in the peritoneal wash. A review of world literature on the 56 cases reported so far is presented where occasional cases showing disease spread have been reported, suggesting caution in the management and follow‐up of this clinicopathologic entity. J. Surg. Oncol. 2000;74:297–299.

Immunophenotypic Characterization of Benign and Malignant Prostatic Lesions

BACKGROUND Biopsy diagnosis is the gold standard for differentiating benign and malignant prostatic enlargements. This study was aimed at supplementing biopsy diagnosis with immunophenotypic characters of prostatic lesions. METHODS Twenty five cases each of nodular hyperplasia and adenocarcinoma prostate were compared for their morphologic appearances and immunophenotyping, by studying antibodies to prostate specific antigen (PSA), transglutaminase, chromogranin and high molecular weight keratin, proliferating cell nuclear antigen, cell death (apoptosis) and neovascularisation (CD 34). RESULTS Markers of differentiation (PSA and transglutaminase) aided recognition of higher-grade tumours. PSA negativity avoided metaplasia being overcalled as carcinoma. Loss of basal cells around malignant prostatic acini as determined by high molecular weight keratin (HMWK), was useful in foci of atypical small acinar proliferation and in prostatic intraepithelial neoplasia. Assessment of proliferation indices identified subsets of tumours, within conventional morphologic Gleasons grades, with a higher growth fraction. Cell death determination and study of tumour vessels did not offer any improvement on morphology. CONCLUSION Immunophenotypic assessment helps in refining morphologic diagnosis of prostatic lesions. Differentiation and proliferation markers objectively assess tumour characteristics with their biologic growth potential and are recommended for diagnostic use. They also help in assessement of response to therapy.

Secretory meningioma mimicking malignancy

Meningiomas are common tumours of the central nervous system (CNS) and majority of them are benign (World Health Organisation Grade 1) [1]. Among the variants, secretory meningioma (SM) is recognized by its gland-like formations [2], which mimics metastasis of adenocarcinoma to the brain. It is also known to be vascular and produces significant peritumoural brain oedema (PTBE) leading to increased perioperative morbidity. These characteristics justify its recognition, to prevent misdiagnosis by the pathologist and care during resection by the neurosurgeon.

Melanoma : A Frequently Missed Diagnosis

In ‘An unforgivable delay’ in the Lancet 2005 Jan 29 issue, a psychiatrist acknowledges, how as a young internist he dismissed an inguinal soft tissue swelling in a middle-aged lady, as a ‘lipoma’ and to his chagrin, realized later, that it was a melanoma! [1]. The confessional prompted this review in view of recent similar experiences with diagnosis of this tumor. Malignant melanoma is an aggressive tumor of melanocytes commonly encountered as cutaneous malignant melanoma (CMM) in fair-skinned individuals predisposed to it by ultraviolet exposure. Fewer cases present as ocular melanomas or malignant mucosal melanoma (MMM) [2, 3]. India enjoys a low incidence of melanoma [4, 5, 6], which could be due to under-reporting of melanoma on account of a low index of suspicion by clinicians and pathologists alike. This is particularly true when a cutaneous lesion lacks pigmentation or an ocular or mucosal melanoma is occult and presents as metastasis. This may lead to a missed or delayed diagnosis and delayed therapy. We draw the attention of the reader to the possible underreporting of melanoma because of our reluctance to ‘think’ about its existence; compounded by a variant morphology that evades diagnosis. Four recent cases highlighting the clinical and diagnostic aspects of melanoma are discussed.

Acute Bilateral Hypopyon in Acute Lymphocytic Leukaemia

Acute lymphocytic leukaemia (ALL) is a malignant clonal disorder of the bone marrow lymphopoietic precursor cells, characterized by accumulation of lymphoblasts that lack the potential for differentiation and maturation [1]. These abnormal cells spill into the circulation and infiltrate other organs such as the liver, spleen, central nervous system (CNS) and the eye. Presence of intraocular leukaemic infiltrates correlates with CNS involvement and with decreased survival [2, 3]. Ocular manifestation may be the only sign of leukemic relapse or may present several months prior to systemic relapse. Hence, prompt anterior chamber aspiration is required for the correct diagnosis and treatment.

ASTROCYTOMAS AND PROGNOSIS-FROM MORPHOLOGY TO TUMOR BIOLOGY

Twenty-seven cases of Astrocytoma were studied to assess the role of a newly introduced proliferation marker-Proliferating Cell Nuclear Antigen (PCNA) in improving prognostic accuracy in comparison to traditional histologic methods like grading. The study revealed a direct correlation between grading and PCNA expression as determined by labelling indices (LI). A 25% PCNA LI separated low and high grade tumors. The difference between PCNA LIs of patients who were alive and those who were dead at the end of the study was statistically significant. However, in this study with limited follow-up, statistically significant relation to survival and recurrence could not be established. The study introduces a new method of assessing tumor biology that enables objectivity in prediction of tumor behaviour.