Chondroblastoma: a clinico-pathological analysis

To determine the clinico-pathological and histological features of Chondroblastoma [CB]. Case series. The Aga Khan University Hospital, Karachi, from 2000 to 2013. The histological slides of all reported cases of CB were retrieved and reviewed for morphological features. Clinical features were noted from surgical pathology reports. Frequency of features was noted. Sixty one cases of CB were identified. Pain was the most common presenting symptom. The age ranged from 10 to 38 years [mean 20 +/- 1.98 years; M: F 2.5:1] with 61% patients in the second decade of life. Forty six cases occurred in long tubular bones; distal femur being most common site. Metaphysis, clavicle, temporal bone and metacarpal were also involved. Histologically, all CBs were composed of round to polygonal cells and scattered osteoclast-type multinucleated giant cells and majority had hemosiderin pigment. Chicken-wire calcifications and coarse calcifications were seen in 85% and 26% of cases respectively. A spindle cell component was seen in 54% of cases. ABC-like areas were seen in 10 cases. Mitosis ranged from 1 to 6/10 HPFs. Recurrence was seen in 2 cases. Recurrent tumor showed similar morphology when compared with the initial tumor. CB is a benign tumor but has potential for recurrence. Males are more affected, second decade is more common and distal femur is most common site. Metaphysis, clavicle, temporal bone and metacarpal were the rare sites of CB. Histological features predictive of recurrence were not separately identified

Non-hodgkin lymphoma [NHL] in Pakistan

Lymphomas are classified as Hodgkin's and Non-Hodgkin's lymphomas [HL; NHL]; NHL being further subdivided into B, T and Null cell categories on the basis of WHO classification. With a few exceptions worldwide, B-NHL are more common, accounting approximately 80-85% of all cases of NHL compared to T-NHL, which accounts for about 10-15% of all NHL cases. The incidence of NHL has shown a steady increase and attention is being focused on the possible causes of this increase. Epidemiologic studies indicate that environmental factors do play a role in the causation of NHL, such as drugs, pesticides, solvents, hair dyes, viruses [EBV, HTLV-1, Hepatitic C and HIV] and Helicobacter pylori. Hence many different environmental factors of risk acting on large segments of the population can contribute for increase of NHL.

Fibrolamellar hepatocellular carcinoma- a rare clinical variant

Fibrolamellar type is a rare variant of hepatocellular carcinoma [FLHCC]. A 20 year old boy presented with pain and mass in the epigastric region for the last six months. Early diagnosis and confinement of the lesion to a lobe made it possible to perform complete resection of tumour along with subtotal gastrectomy. Patient recovered well and was sent to oncologist for further treatment

Immunoproliferative small intestinal disease [IPSID]

This study describes the frequency, demographics, clinical presentation, endoscopic findings, histopathological features, treatment and outcome of 'Immunoproliferative small intestinal disease' [IPSID]. Archives contained a total of 27 cases of IPSID diagnosed and treated over an 18-year period. A M: F ratio of 2.4:1 was seen with a mean and median ages of 28.7 and 25 years. Most patients [68.8%] presented with abdominal pain and diarrhoea. In the majority [62.5%], duodenum was the primary site of involvement. Endoscopy showed polypoidal, raised or flat lesions. Biopsy findings included blunting or flattening of villi with dense plasma cell infiltrate and lymphoepithelial lesions. Twenty-four cases were categorized as stage A and B [benign and intermediate] and three were categorized as stage C [malignant, diffuse large B-cell lymphoma with plasmacytoid features]. Stage A and B patients responded well to antibiotic treatment [tetracycline] with regression of the lesions while for stage C patients standard CHOP chemotherapy was administered

BRCA1 status in Pakistani breast cancer patients with moderate family history

To determine BRCA1 status in breast carcinoma patients of Pakistani origin. Observational study. The Oncology Clinics of the Aga Khan University Hospital, Karachi, between May 2005 and December 2009. Fifty three breast cancer patients based on clinical and laboratory diagnosis were recruited for this study. Moderate family history was defined as having a close relative [mother, daughter, sister] diagnosed with breast cancer under 45 years. Peripheral blood samples were collected from each patient in a 5 ml tube containing EDTA as anticoagulant. Subsequent to DNA extraction, mutational analysis of BRCA1 exons 2, 5, 6, 16, 20 and 22 was carried out using single strand conformation polymorphism [SSCP] assay while protein truncation test [PTT] was used to examine mutations in exon 11. All BRCA1 sequence variants were confirmed by DNA sequencing. Twenty-three patients were diagnosed with early onset breast cancer, 30 patients had moderate family history. At the time of diagnosis, the median age of enrolled patients was 39 years [range 24-65 years]. Out of 53 patients, analyzed by SSCP assay, mobility shift was detected in exon 6, 16 and 20 of three patients, whereas one patient was tested positive for mutation in exon 11 by PTT assays. All patients with BRCA1 mutations were further confirmed by DNA sequencing analysis. In exon 16 c.4837A > G was confirmed, which is a common polymorphism reported in several populations including Asians. Moreover, mutations in exon 6 [c.271T > G], exon 20 [c.5231 delG] and exon 11 [c.1123 T > G] were reported first time in the Pakistani population. Several BRCA1 mutations were observed in Pakistani breast cancer patients with moderate family history. Therefore, mutation-based genetic counselling for patients with moderate family history can facilitate management, if one first or second degree relative or early onset disease is apparent

Gastric MALT lymphoma: a rarity

Association of Helicobacter pylori [H.Pylori] infection with gastric 'Mucosa Associated Lymphoid Tissue' [MALT] lymphomas [MALTomas] is well established. In this study the frequency and characteristics of gastric MALToma over a period of 18 years was evaluated. During this period 24 patients with gastric MALToma were diagnosed; out of them, 13 [54.2%] had active H.Pylori infection. The mean and median age was 49.7 and 53.5 years. The male: female ratio was 17:7. The common presenting complaints were epigastric pain [n=10] and dyspepsia [n=9]. Endoscopic findings revealed mild gastric hyperemia [n=16], superficial erosions [n=4] and superficial ulcers [n=4]. It was concluded that the prevalence of gastric MALToma was very low in contrast to a high H. pylori gastritis in the Pakistani population

Protective effect of zinc over lead toxicity on testes

To determine the effects of lead and zinc on testes. Randomized control trial. Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi, from August 2003 to December 2005. Sixty adult [90 days old] albino rats were obtained from animal house JPMC for the study and divided into 3 groups. Group A received injection normal saline 1 cc intraperitoneally daily for 8 weeks. Group B received lead chloride in a dose of 10 mg/kg body weight intraperitoneally daily. Group C received zinc chloride in a dose of 1 mg/kg body weight before half an hour of injection of lead chloride in a dose of 10 mg/kg body weight intraperitoneally daily so that to provide pre-treatment. On the day of completion of treatment the animals were sacrificed testes removed and fixed in Bouins fluid. Testes were dehydrated in the ascending strength of alcohol, 5 micro m thick sections were cut and stained with PAS Iron Hematoxylin. Student's t-test was used for statistical analysis with significance at p<0.05. The mean diameter of seminiferous tubule was 291.91 +/- 1.18, 198.53 +/- 1.67 and 288.77 +/- 1.11 micro m in groups A, B and C respectively. Diameter of seminiferous tubules decreased by 31.99% in group B [p<0.001; CI 89.023 to 97.736] as compared group A and while group B comparing with group C, the diameter of seminiferous tubules was decreased by 31.25% [p-value=0.076; CI-94.264 to-86.203]. Mean thickness of germinal epithelium was 96.19 +/- 1.01, 50.69 +/- 1.20 and 94.94 +/- 0.54 micro m in groups A, B and C respectively. Thickness of germinal epithelium decreased by 47.30 in group B [P<0.001; CI 42.503 to 48.496] as compared to group A and while comparing group B with group C, the thickness of germinal epithelium was decreased by 46.61% [p=-44.25; CI-46.704 to-41.787]. Zinc prevented toxic effects of lead on germinal epithelium in the albino rats

Model for end-stage liver disease [MELD] score as a useful prognostic marker in cirrhotic patients with infection

To determine the association of Model for End stage liver disease [MELD] score to the outcome of cirrhotic patients with bacterial infection and to compare it with Child-Turcott-Pugh [CTP] score. Descriptive study. The Aga Khan University Hospital, Karachi, from January 2005 to December 2007. Patients with diagnosis of liver cirrhosis and bacterial infection were included. Demographic features, laboratory data and type of infection were recorded. Multiple logistic regression assays were applied to determine the factors associated with poor outcome in cirrhotics with infection. Receiver-Operating Characteristics [ROC] were used to determine the cut-off values of CTP score and MELD score with the best sensitivity and specificity. A total of 530 patients, 313 male [59%] with a mean age of 53 +/- 13 years were analyzed. Spontaneous bacterial peritonitis was the predominant infection seen in 369 [69%] patients. One hundred and eighty six [35%] patients died. Factors associated with poor outcome were a CTP score of more than 11 [p=0.001], raised blood urea nitrogen [p=0.020], raised creatinine [p=0.004], shock [p=0.002], and MELD score > 22 [p=0.03]. An eight percent increase in mortality rate was noticed with every one point rise in MELD score above 22. ROC curve showed that the specificity of CTP and MELD score to predict poor outcome in these patients was 36% and 59% respectively. Child-Turcott-Pugh score more than 11, raised BUN and creatinine, shock and high MELD score were poor prognostic markers in cirrhotic patients with infection. MELD score had better specificity than CTP score in determining outcome

Comparison of complications of septal surgery with and without use of intra-nasal splints

To compare the adhesion formation and post-operative pain with and without intranasal splints in patients undergoing septal surgery with inferior turbinectomy. Comparative study. The study was carried out in CMH Rawalpindi from April2005 to Oct 2005. Total 60 patients undergoing septal surgery were randomly divided into two groups. In Group A intranasal splints [made from plastic infusion bottles] were placed with paraffin gauze packing and in Group B, paraffin gauze packing was done without intranasal splints. Follow-up was carried out at 48 hours and 01 week after surgery for assessment of pain scores, while adhesion formation was monitored for two months after surgery. Mean age of patients in Group A [with splints] was 26.43 years and of Group B [without splints] was 25.77 years. There was marked difference of pain scores at 48 hrs after surgery between two groups and difference was found highly significant [p value 0.001]. The p-value of pain score for data at one week was 0.022, still significantly different but lesser than the one at 48 hrs. Only two patients both without splints were found to have adhesions [p value 0.150]. It is concluded that intranasal splints increased post-operative pain significantly and there was no significant benefit in reducing the post-operative adhesion formation with splints

Hepatic angiosarcoma with metastasis to small intestine

Hepatic angiosarcomas are rare tumours with poor prognosis, with patients usually dying within 6 months. Metastases mainly occur in lymph nodes, spleen, lungs, bones and adrenals. Metastasis to small intestine is even rarer. Similarly, primary or metastatic angiosarcomas in small intestine are extremely rare, often present with recurrent gastrointestinal bleeding and anemia, and have an extremely poor prognosis. Both primary or metastatic intestinal angiosarcomas may exhibit epithelioid morphology. It may be very difficult to differentiate between primary and secondary cases in intestine and especially when the tumour exhibits epithelioid morphology

Comparative predictive value of three prognostic markers, s-phase fraction, PCNA and mitotic count on axillary lymph node metastasis in carcinoma breast

Axillary lymph node metastasis is the single most important prognostic factor in carcinoma of the breast. Therefore, prognostic markers that may reliably predict probability of lymph node [LN] metastases are of great value. This study was conducted to compare the predictive value of two novel prognostic/ proliferative markers i.e. S-phase fraction [SPF] and proliferating cell nuclear antigen [PCNA] in parallel with mitotic index. Data of consecutive cases of infiltrating ductal carcinoma [IDC] breast diagnosed from July 2003 to July 2004 at the section of the Histopathology, The Aga Khan University Hospital, Karachi, were reviewed. A total of 112 cases of infiltrating ductal carcinoma [IDC] of the breast with axillary LN sampling were selected. SPF was calculated by flow cytometry while PCNA staining was done by immunohistochemistry. Mitotic count was calculated according to modified Bloom and Richardson's grading guidelines. It was observed that the number of axillary LN was found between the results of various categories of PCNA on axillary LN metastases [p value: 0.182] and mitotic count with axillary lymph node metastases [p value: 0.324]. It was concluded that mitotic count and /PCNA alone cannot be used in predicting axillary LN metastases. SPF was found to be a more reliable marker compared to PCNA reactivity and conventional mitotic count in predicting axillary LN metastases

Frequency of primary solid malignant neoplasms in both sexes, as seen in our practice

To determine the frequency of various histologic types of primary solid malignant neoplasms in males and females, in our practice, in a large series of surgical biopsies. A retrospective study of 20,000 consecutive surgical biopsies in the section of Histopathology, Aga Khan University Hospital [AKU], Karachi, in 2004. Squamous cell carcinoma of oral cavity was the commonest malignant neoplasm in males followed by diffuse Large B cell, Non-Hodgkin's lymphoma and Prostatic adenocarcinoma. In females, infiltrating Ductal carcinoma of the breast was overwhelmingly the commonest malignant neoplasm followed by Squamous cell carcinoma of the oral cavity and esophagus. Out of 20,000 biopsies, there were 4616 [23.08%] malignant neoplasms. Carcinoma of oral cavity is very common in our population in both sexes

Frequency of primary solid malignant neoplasms in different age groups as seen in our practice

To determine in a large series of surgical biopsies, the frequency of various histologic types of primary solid malignant neoplasms in males and females in different age groups. A retrospective study of 20,000 consecutive surgical biopsies reposted in the section of histopathology, AKU in 2004. Malignant neoplasms are commonest in the fifth and sixth decades of life. The commonest malignant neoplasms in the first decade were Hodgkin's lymphoma and Wilm's tumor in males and females respectively. In the second decade, osteosarcoma in males and Ewing's sarcoma/PNET in females. In the third decade, colorectal adenocarcinoma in males and infiltrating Ductal carcinoma of breast in females. In the fourth decade, squamous cell carcinoma of oral cavity in males and infiltrating ductal carcinoma of breast in females. In the fifth decade squamous cell carcinoma of oral cavity in males and infiltrating ductal carcinoma of breast in females. In sixth decade, squamous cell carcinoma of oral cavity in males and infiltrating ductal carcinoma of breast in females and in the seventh decade, prostatic adenocarcinoma in males and infiltrating ductal carcinoma of the breast in females. Above age of 70 years, the commonest malignant were again prostatic adenocarcinoma in males and infiltrating ductal carcinoma of breast in females. Malignant neoplasms are commonest in the fourth, fifth and sixth decades of life

Coexistence of caseating granulomas with hodgkin's lymphoma: a diagnostic and clinical dilemma

Hodgkin's lymphoma [HL] is a neoplasm of the B lymphocytes. The histological picture may resemble granulomatous lesions similar to those seen in tuberculosis as collections of epitheloid cells are not uncommonly seen in HL. In areas which are endemic to tuberculosis, the close association and the coexistence of the two must be recognized for the proper diagnosis and treatment of the illness. A series of cases of Hodgkin's lymphoma is reported in which the biopsy specimens from different parts of the body portrayed caseating granulomatous lesions

Plaque formation reduction with glutathione monoester in mice fed on atherogenic diet

To determine the role of glutathione monoester on reducing the development of plaque formation in an animal model. Laboratory control trial. Aga Khan University, Karachi, from January 2004 to December, 2004. Twenty-four Balb/c mice were divided into 3 equal groups. First group was fed on atherogenic diet alone, while the second group received atherogenic diet plus twice weekly injections of glutathione monoester. The third group was fed on normal diet for mice. After one year, the animals were sacrificed. Blood was analyzed for lipid levels, while liver, kidney, spleen, heart and aorta were removed to study morphological changes. In the groups of mice receiving atherogenic diet [with and without glutathione monoesters], there was significant increase in levels of total cholesterol [p=0.011] and LDL cholesterol [p=0.001] compared to levels of these lipids in mice on normal diet. However, a significant decrease in levels of triglycerides [p=0.01] was observed in the group receiving atherogenic diet along with glutathione monoester. Supplementation with glutathione monoester had the most pronounced effect only on triglyceride levels. Atherosclerotic plaques were seen in heart and/or aorta of mice receiving atherogenic diet. However, such plaques were either totally absent or if seen in an animal, were extremely small and diffuse in the group receiving glutathione monoester along with atherogenic diet. Mice on normal diet had no evidence of any plaque formation. Cholesterol granuloma was seen in liver of mice on atherogenic diet alone. In mice receiving atherogenic diet plus glutathione monoester, no cholesterol granuloma was found in liver. There were no remarkable morphological changes in spleen and kidney in the three groups of mice. Glutathione monoester appears to inhibit or reduce the development of plaque formation in mice

Medullary carcinoma of breast with a novel germline mutation 1123T>G in exon11 of brca1

Breast cancer, the most common malignancy in females, has an estimated 5-10% hereditary predisposition. BRCA1 is a tumor suppressor gene and is known to be responsible for breast cancer and breast-ovarian cancers running in families. In breast caner patients, several mutations in BRCA1 have been reported throughout the gene. This report describes identification of a mutation in BRCA1 gene using protein truncation [PTT] assay in a patient with medullary carcinoma of breast who also had a family history of breast cancer. Following DNA sequencing, the mutation was confirmed as substitution of thymine at position 1123 with guanine of exon 11 [1123 T>G]. This mutation can be added to the pool of known BRCA1 mutations in Pakistani population, which will help in developing a local screening panel of BRCA1 mutations

Small B cell Non-Hodgkins Lymphoma in Pakistan

To study the pattern of small B cell lymphomas in Pakistan. This descriptive study was carried out at the Aga Khan University Hospital pathology department including 1721 cases of Non-Hodgkins Lymphoma [NHL] diagnosed during a period of five years [1998-2002] and classified according to REAL/WHO classification. The antibodies used included Leukocyte Common Antigen [LCA], Pan B [CD20, CD79a], Pan T [UCHL-1], Bcl 2, Mib 1[Ki 67] and Cyclin D1 [Dako, Denmark]. Out of the 1721 NHL cases, only 140 [8.1%] could be categorized as small B-cell NHL. The study group comprised small lymphocytic lymphoma/chronic lymphocytic leukemia [58 cases; 41.4%] followed by follicular lymphoma [46 cases; 32.9%], mantle cell lymphoma [15 cases; 10.7%], extra nodal marginal zone B cell lymphoma of MALT type [15 cases; 10.7%], lymphoplasmacytic lymphoma [5 cases; 3.6%] and splenic marginal zone B-cell lymphoma [1 case; 0.7%]. No case of nodal marginal zone lymphoma was diagnosed. The age ranged from 18 to 98 years with a mean and median of 54.64 and 58.50 years respectively. Small B-cell NHL was more common in males; with male to female ratio of 2.1. Majority of the small B-cell NHL were nodal at presentation with a nodal to extranodal ratio of 3.4. It is concluded that the frequency of these small B-cell NHL is very low in our population in contrast to the western literature. Further studies based on epidemiologic and etiological factors are required to look into this marked difference of occurrence of these indolent lymphomas

Frequency and characteristics of breast lymphomas presenting to a tertiary care hospital Pakistan

To assess the relative frequency of [primary and secondary] mammary lymphomas presenting to a tertiary care hospital, Pakistan and its categorization according to WHO classification of lymphoid neoplasms. All NHLs [nodal and extra nodal] diagnosed in the section of histopathology during 1992-2004 were retrieved and reviewed. All patients [n=30] diagnosed with lymphomatous involvement of the breast were selected. Distinction between primary and secondary breast lymphomas was not made owing to lack of availability of clinical information. A total of 5637 breast malignancies were diagnosed in our department during the study period of 10 years and the total number of NHLs [Nodal and extra Nodal] was 2632. Thirty [n=30] patients accounting for 1.13% were diagnosed to have lymphomatous involvement of the breast. The Female to Male ratio was13.5:1; age range was 12-92 years with a median age of 43 years [Mean age 46.5 years and Standard deviation of age was 16.88 years]. The sites of the lesions were the right breast in 11 cases [37.93%], left breast in 9 cases [31.03%] and both breasts in 2 cases [6.89%], while the location of 8 masses [27.58%] was unknown. Immunohistochemical studies were negative for cytokeratins [MNF and Cam 5.2] in all cases. All cases of DLBCL expressed B cell lineage antigens and were positive for LCA and Pan B [CD20 and 79a]. We concluded that breast lymphomas represent 1.13% of all NHL and 0.5% of all breast malignancies in this study. The most frequent morphologic type was diffuse large B-cell lymphoma. As patients with primary breast lymphoma have a better prognosis than those with carcinoma of the breast or patients with extranodal lymphomas, a multidisciplinary approach including surgery, radiotherapy, and chemotherapy when needed would result in a more favourable outcome

Uterine perivascular epithelioid cell tumour presenting as a cervical mass

Perivascular Epithelioid Cell Tumour [PEComa] also known as myelomelanocytic tumours are uncommon, recently described mesenchymal tumours that include angiomyolipoma, clear cell "sugar" tumour of the lung, lymphangioleiomyoma and tumours composed predominantly of epithelioid cell morphology. A predilection for uterus has been described. However up till now only 14 cases of uterine PEComas have been described. All of these were seen in adult females in the peri and post menopausal age group [from 40-75years], and almost all were located in the region of body of uterus. A single case in the upper cervical region has been reported with uterine PEComatoses. We report an unusual presentation of this rare tumour presenting as a polypoidal cervical mass in a young female. Occurrence of this tumor in a young female as seen in our case warrants inclusion of PEComa in the diferential diagnosis of all epithelioid and clear cell neoplasms of uterus irrespective of age