Tumors of dendritic reticulum cells are rare neoplasms that exhibit significant morphologic overlap with other malignancies. Fine-needle aspiration cytologic appearances of this neoplasm are not well understood. A 33-yr-old woman presented with a rapidly growing nodular mass in the right upper cervical region and right-sided ptosis. Fine-needle aspiration cytology of the mass showed dissociated as well as clustered, large, polygonal cells that showed high nuclear-cytoplasmic ratio. Nuclei were round, oval, or irregular in shape. Large and small blastoid forms with prominent nucleoli and chromatin clumping as well as binucleated cells and cells with lobulated nuclei were seen. Numerous mitoses were observed. The tumor cells expressed focal immunocytochemical reactivity to CD45 and CD68, but were negative for CD2, CD3, CD4, CD8, CD20, CD30, CD45RO, epithelial membrane antigen (EMA), cytokeratin, and HMB45. Histologic sections of the biopsy from the growth showed nodal tissue effaced by a tumor composed of large, pleomorphic neoplastic cells with some binucleate and multinucleate forms resembling Reed-Sternberg cells. The intervening stroma contained numerous small lymphocytes. Tumor cells expressed vimentin, S-100 protein, CD68, and MAC387, but were negative for LCA, CD1a, CD3, CD15, CD20, CD21, CD23, CD30, CD35, carcino-embryonic antigen, HMB45, cytokeratin AE1/3, EMA, myeloperoxidase, lysozyme, smooth-muscle actin, and desmin. The combined histologic and immunohistologic features suggested a histiocytic/dendritic reticulum cell neoplasm and a diagnosis of interdigitating dendritic reticulum cell sarcoma was made.
A 62-year-old lady presented with a six-month history of swelling of the left upper eyelid, resulting in mild mechanical ptosis. Clinical assessment suggested a provisional diagnosis of dermoid cyst. The lesion was excised and histology revealed nodular deposits of amorphous eosinophilic material surrounded by lymphocytes and plasma cells. Special histochemistry and immunoperoxidase stain results showed deposition of amyloid, non-AA type. The lesion recurred 6 months later.
Angiosarcoma of the breast is an extremely rare condition. This case illustrates the use of embolisation as a modality of treatment for primary breast angiosarcoma. No other case has been reported on the use of embolisation for this disorder.
Hepatocellular carcinoma (HCC) is among the ten most common cancers in Malaysian males. As cellular proliferation is an important feature of malignant transformation, we studied the proliferation pattern of normal and benign perineoplastic liver versus hepatocellular carcinoma in an attempt to further understand the tumour transformation process. 39 HCC (21 with accompanying and 18 without cirrhosis) histologically diagnosed at the Department of Pathology, University of Malaya Medical Centre between January 1992 and December 2003 were immunohistochemically studied using a monoclonal antibody to PCNA (Clone PC10: Dako). 20 livers from cases who had succumbed to traumatic injuries served as normal liver controls (NL). PCNA labeling index (PCNA-LI) was determined by counting the number of immunopositive cells in 1000 contiguous HCC, benign cirrhotic perineoplastic liver (BLC), benign perineoplastic non-cirrhotic (BLNC) and NL cells and conversion to a percentage. The PCNA-LI was also expressed as Ojanguren et al's grades. PCNA was expressed in 10% NL, 38.9% BLNC, 76.2% BLC and 71.8% HCC with BLNC, BLC and HCC showing significantly increased (p < 0.05) number of cases which expressed PCNA compared with NL. The number of BLC which expressed PCNA was also significantly increased compared with BLNC. PCNA-LI ranged from 0-2.0% (mean = 0.2%) in NL, 0-2.0% (mean = 0.3%) in BLNC, 0-3.6% (mean = 0.7%) in BLC and 0-53.8% (mean = 7.6%) in HCC with PCNA-LI significantly increased (p < 0.05) only in HCC compared with BLC, BLNC and NL. Accordingly, all NL, BLC and BLNC showed minimal (<5% cells being immunopositive) immunoreactivity on Ojanguren et al's grading system and only HCC demonstrated immunoreactivity which ranged up to grade 3 (75% of cells). From this study, there appears to be a generally increasing trend of proliferative activity from NL to BLNC to BLC and HCC. Nonetheless, BLNC and BLC, like NL, retained low PCNA-LI and only HCC had a significantly increased PCNA-LI compared with the benign categories. This is probably related to the malignant nature of HCC and may reflect the uncontrolled proliferation of the neoplastic hepatocytes.
This is a case report of 16-year-old adolescent school boy who died due to unusual calcification of coronary arteries. He died while cycling with his friends. While cycling fast he fell. He was brought dead to hospital. At times unsuspected cardiac lesions cause sudden death during extraneous physical activities in healthy persons. Sudden death in adolescents is not very common. It is an unusual case as apparently healthy adolescent boy actively participating in sports had stony hard coronary arteries. The coronaries showed advanced calcification and early bone formation. The myocardial septum had extensive fibrosis. The pathogenesis and other possible similar conditions are also discussed in the report.
Transaminase enzymes, alanine (ALT) and aspartate transaminase (AST), have been reported to be raised and implicated to have prognostic value in hepatocellular carcinoma (HCC). Ki67, a marker of cellular proliferative activity, has also been noted to be increased in HCC. A study was conducted at the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur to determine the possible association of proliferative activity, as determined by Ki67, with the transaminase enzymes. 31 cases of histologically diagnosed HCC who underwent tumour resection were retrieved from departmental archives. The patients' ages ranged between 40 to 79 years with a mean of 58.3 years. There was a male preponderance with M:F = 2.9:1. Ethnic Chinese formed 83.9% of the cases. 4 microm sections, cut from the formalin-fixed, paraffin-embedded tumour tissue block of each case, were immunohistochemically stained with Ki67 (DAKO monoclonal MIB-1) using the commercial DakoCytomation EnVision+System-HRP kit. The latest ALT and AST levels, assayed within 7 days prior to tumour resection, were retrieved from the patients' case records. 24 (77.4%) HCC demonstrated elevation of either ALT and/or AST. 27 (87.1%) HCC were immunopositive for Ki67. Ki67 immunoexpression was significantly correlated with raised transaminases (p<0.05). Hypothetically, the mechanism by which this phenomenon may occur may simply be release of transaminases due to destruction of hepatocytes by the cancer. Thus rising levels of the transaminases could signal a more rapid growth of the tumour and these routinely performed tests can be of prognostic value in management of HCC patients.
Extramedullary plasmacytoma is a rare plasma cell proliferative disorder with a predilection for the head and neck region. Occasionally, it presents as a solitary lesion in the nasal cavity. We report a case of an isolated lesion in the middle turbinate of the right nasal cavity. The lesion was completely excised via an endoscopic approach. We also review the pathology and management of plasmacytomas in general.
Extra-adrenal paragangliomata are uncommon entities. They can be classified into four basic groups according to their anatomical sites, i.e. branchiomeric, intravagal, aorticosympathetic and visceral autonomic. Similar tumours may arise in sites away from the usual distribution of the sympathetic and parasympathetic ganglia, e.g. orbit, nose, small intestine and even in the pancreas. We report three instructive cases of extra-adrenal paraganglioma which were found in unusual sites such as urinary bladder, thyroid gland and on the wall of the inferior vena cava.
An aneurysmal bone cyst is a rare bone lesion. Its origin and precise nature remain unknown. It is seen as a locally-destructive, rapidly expandable, benign multicystic mass. We report a 17-year-old boy with an aneurysmal bone cyst of the maxilla, with extensive local involvement and bony destruction that was treated surgically. There was no recurrence noted after four years of follow-up.
Epidermal inclusion cyst (EIC) arising from the breast is an uncommon benign condition. We report two cases of enlarging EIC of the breast in two women in their forties. The diagnosis of this condition may not be straightforward with imaging alone if an EIC presents as an enlarging lump in the breast and mimics a benign breast lesion, most commonly a fibroadenoma or malignant lesion with benign imaging features. Excision is usually recommended for a definite histopathological diagnosis and for the prevention of potential risks of malignant transformation. Asymptomatic stable lesions do not require treatment; biopsy is unnecessary, and follow-up imaging suffices if typical sonographic and clinical findings are found.
A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.
Olfactory neuroblastoma is a rare, slow growing, malignant tumour of neuroectodermal origin that begins in neuroepithelial cells of the olfactory membrane. A metastatic rate of 20% to 60% is reported with the most common site being the cervical lymph node. Other sites include the parotid glands, skin, lungs, bone, liver, orbit, spinal cord and spinal canal. We describe a case of olfactory neuroblastoma presented to us with scalp metastasis.
Estrogen receptor (ER) positive rates in breast cancer may be influenced by grade, stage, age and race. This study reviews the ER positive rates over a 15-year period at the University Malaya Medical Centre, Kuala Lumpur, Malaysia. Data on ER status of 3557 patients from 1994 to 2008 was analyzed. ER status was determined by immunohistochemistry with a cut-off point of 10%. ER positivity increased by about 2% for every 5-year cohort, from 54.5% in 1994-1998 to 58.4% in 2004-2008. Ethnicity and grade were significantly associated with ER positivity rates: Malay women were found to have a higher risk of ER negative tumors compared with Chinese women. Grade 1 cancers were nine times more likely to be ER positive compared with grade 3 cancers. In summary, the proportion of ER positive cancers increased with each time period, and ethnicity and grade were independent factors that influenced ER positive rates.
Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profiles of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplification by FISH, a small but certain percentage of patients would miss the benefit of anti-c-erbB-2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to significant ramifications on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.
Secondary involvement of the urinary bladder in non-Hodgkin's lymphoma is relatively common; however, primary malignant lymphoma of this organ is extremely rare. The most common type of primary bladder lymphoma is a low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. We report here on the imaging findings of a primary bladder lymphoma with bone marrow infiltration.
On integration into the host cervical keratinocyte genome, human papillomavirus (HPV) E7 protein binds pRB,releasing E2F from normally incompetent pRB-E2F complexes and allowing propagation of G1-S transition by the E2F. p16(INK4a), a tumour suppressor protein, increases in reflex response to counter this. 29 histologically re-confirmed low-grade squamous intraepithelial lesions (LSIL), 27 high-grade squamous intraepithelial lesions (HSIL) and 30 invasive cervical squamous carcinoma (SCC) were immunohistochemically stained for p16(INK4a) expression using the CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany) to re-affirm the notion that integration of HPV occurs predominantly in SCC and possibly HSIL and less in LSIL and normal squamous epithelium (NSqE). Implicit was also the attempt to understand the role of E2F, as indicated by p16(INK4a), in evolution of SCC from HSIL. No ethnic predilection was noted for LSIL, HSIL or SCC. Patients with SCC were significantly older by about 14-years compared with HSIL (p < 0.05) while there was no significant age difference between HSIL and LSIL. p16(INK4a) expression was significantly increased (p < 0.05) in both HSIL (88.9%) and SCC (83.3%) compared with LSIL (3.4%) and NSqE (0%); the NSqE being normal squamous epithelium noted in 17 of the LSIL, 19 HSIL and 5 SCC. From these findings there is suggestion that fundamental upstream events viz HPV integration, E7 upregulation followed by E2F activation occurs at point of transformation to HSIL and continues unrelentingly for another one to two decades before hitherto unclear factors convert a non-invasive lesion into an overtly invasive malignant counterpart. Interestingly, the occurrence of HSIL and LSIL in almost the same age group could mean that alteration from episomal to integrated form of HPV may not incur a prolonged incubation period, unlike from HSIL to SCC.
Endocervicosis in the urinary bladder is a rare benign condition. We present a case in a 37-year-old woman with classical clinical and pathological features of endocervicosis. The unusual observation of endocervical-like mucinous epithelium in continuity with the urothelium in addition to fully developed endocervicosis prompted immunohistochemical profiling of the case using antibodies to cytokeratins (AE1/AE3, CK19, CK7, CK5/6, CK20), HBME-1, estrogen receptor (ER) and progesterone receptor (PR) to assess the relationship of the surface mucinous and endocervicosis glandular epithelia. The surface mucinous epithelium, urothelium and endocervicosis glands were immunopositive for AE1/AE3, CK7 and CK19 while CK20 was only expressed by few urothelial umbrella cells. The surface mucinous epithelium was CK5/6 and HBME-1 immunonegative but showed presence of ER and PR. This was in contrast to the urothelium's expression of CK5/6 but not ER and PR. In comparison, endocervicosis glands expressed HBME-1, unlike the surface mucinous epithelium. The endocervicosis epithelium also demonstrated the expected presence of ER and PR and CK5/6 immunonegativity. The slightly differing immunohistochemical phenotypes of the surface mucinous and morphologically similar endocervicosis glandular epithelium is interesting and requires further clarification to its actual nature. The patient has remained well and without evidence of disease 18-months following transurethral resection of the lesion.
INTRODUCTION: The age standardised incidence rate (ASR) of breast cancer in Malaysia which is a high middle- income country is similar to Indonesia, a low middle-income country. (Globocan 2008) It is however unknown whether the presentation of breast cancer differs between these two countries.
OBJECTIVE: We compared the stage, age at presentation, and pathological characteristics of breast cancer between two tertiary hospitals in Indonesia and Malaysia; Dharmais Cancer Centre (DCC), which is the national cancer referral centre in Indonesia, and University Malaya Medical Centre (UMMC), which is an academic hospital with established breast oncology services in Kuala Lumpur. One thousand, one hundred and fourteen consecutive women (477 in UMMC: 637 in DCC) who were newly diagnosed with breast cancer between January and December, 2010 were included. Patient's age, TNM stage at presentation, and pathological characteristics were compared. Estrogen receptor (ER) and progesterone receptor (PR) were considered positive if 10% or greater of invasive cell nuclei were stained while HER2 was considered positive with an immunohistochemistry staining intensity of 3+ . Logistic regression analyses were performed to identify differences.
RESULTS: Median age at diagnosis was 52 years in UMMC and 47 years in DCC, whereby patients in DCC were more likely to be very young at diagnosis (aged < 35 years) compared to their counterparts in UMMC (Odds ratio (OR): 2.09; 95%CI: 1.32-3.31). Approximately one third of patients in UMMC presented with TNM stage III or IV, compared to 63% in DCC. Patients in DCC were three times more likely to present with metastatic breast cancer compared to patients in UMMC (OR: 3.01; 95% CI: 2.02-4.48). The percentage of low grade tumours in DCC was higher than in UMMC (28% vs 11% respectively), and the difference persisted even after multivariate adjustment. Although the frequency of ER and PR positivity appeared to be higher in UMMC (65% and 55% respectively) compared to DCC (48% and 40% respectively), these differences were not statistically significant following adjustment for age, stage, HER2 status and grade. The frequency of HER2 positivity was 45% in DCC compared to 26% in UMMC, and remained significantly higher even after multivariate adjustment (multivariate OR:1.76; 95%CI:1.25-2.47, in DCC compared to UMMC). The proportion of triple negative breast cancer was however similar in the two centres (19% in UMMC vs 21% in DCC).
CONCLUSION: Indonesian women with breast cancer seem to present at a younger age and at later stages compared to Malaysian women. Their tumors were more likely to be of low grade and HER2 positive, even after adjustment for other factors, while hormone receptor positivity proved similar in the two groups. The higher HER2 positivity rate in Indonesian patients warrants further study.
Melanoma is a lethal skin cancer that occurs predominantly among Caucasians. In Malaysia, the incidence of melanoma is low. This is a retrospective study of clinical and histopathological features of patients with cutaneous melanoma who were seen at the University Malaya Medical Centre from 1998 to 2008. Thirty-two patients with cutaneous melanoma were recorded during that period. Of these, 24 had sought treatment at the onset of disease at our centre. Chinese patients constituted the largest group (19 cases). The median age of these 24 patients at the time of presentation was 62 years. 16 patients had melanoma involving the lower limb with 12 affecting the sole of the foot. None had melanoma arising from the face. Histopathology showed nodular melanoma in 22 cases (91.6%), with superficial spreading and acral lentiginous melanoma diagnosed in 1 case each. The majority of patients (62.5%) were found to be in Stage III of the disease at the time of diagnosis.
The ER-/PR+ breast tumor may be the result of a false ER negative result. The aim of this study was to investigate whether there is a difference in patient and tumor characteristics of the ER-/PR+ phenotype in an Asian setting. A total of 2629 breast cancer patients were categorized on the basis of their age, ethnicity, tumor hormonal receptor phenotype, grade and histological type. There were 1230 (46.8%) ER+/PR+, 306 (11.6%) ER+/PR-, 122 (4.6%) ER-/PR+ and 972 (37%) ER-/PR-. ER-/PR+ tumors were 2.5 times more likely to be younger than 50 years at diagnosis (OR: 2.52; 95% CI: 1.72-3.67). Compared to ER+/PR+ tumors, the ER-/ PR+ phenotype was twice more likely to be associated with grade 3 tumors (OR:2.02; 95%CI: 1.00-4.10). In contrast, compared to ER-/PR- tumors, the ER-/PR+ phenotype was 90% less likely to be associated with a grade 3 tumor (OR: 0.12; 95%CI:0.05-0.26), and more likely to have invasive lobular than invasive ductal histology (OR: 3.66; 95%CI: 1.47-9.11). These results show that the ER-/PR+ phenotype occurs in a younger age group and is associated with intermediate histopathological characteristics compared to ER+/PR+ and ER-/PR- tumors. This may imply that it is a distinct entity and not a technical artifact.