Extramedullary CD20-positive B-lymphoblastic lymphoma in a 5-year-old child: A diagnostic challenge.

INTRODUCTION: Lymphoblastic leukaemia/lymphoma may present as an isolated extramedullary mass, which includes the musculoskeletal region involvement with normal or near-normal blood counts. The tumour may be in the form of B or T-lymphoblastic leukaemia/lymphoma. The clinical features and histological morphology of extramedullary B-lymphoblastic lymphoma (B-LBL) may mimic mature B-cell neoplasms, thus posing a diagnostic challenge. Arriving at the right diagnosis is crucial because these two diseases differ in their prognosis and management. A high index of suspicion is therefore important so as not to miss the correct diagnosis. The diagnosis may be overlooked because the clinical presentation may not be typical of B-LBL or the blood counts do not show any abnormalities. In this report, we highlight one such case where the diagnosis of B-LBL was missed because of its atypical presentation.

Characterisation of immunogenotypes of diffuse large B-cell lymphoma.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive type of non-Hodgkin lymphoma with variable clinical outcomes. The immunogenotypic features of this heterogeneous disease in Malaysia were not well characterized. MATERIALS & METHODS: In total 141 local series of DLBCL cases from UKM Medical Centre were retrospectively studied. RESULTS: Of these cases, we classified our patients into two subtypes: 32.7% (37/113) GCB and non-GCB 67.3% (76/113) by Hans algorithm and the results showed strong agreement with the results by Choi algorithm (κ = 0.828, P<0.001). Survival analysis indicated significant difference in between GCB and non-GCB subtypes (P=0.01), elevated serum LDH (P=0.016), age more than 60-year-old (P=0.021) and the presence of B symptoms (P=0.04). We observed 12% DLBCL cases were CD5 positive and 81.8% of them died of the disease (P=0.076). Analysis on the dual expression of MYC/BCL2 revealed that there is no significant difference in DE and non-DE groups (P=0.916). FISH study reported there were 9.22% (13/141) rearranged cases observed in our population at which highest frequency of BCL6 gene rearrangement (76.9%), followed by MYC (15.4%) and BCL2 (7.7%); no BCL10 and MALT-1 gene rearrangement found regardless of using TMAs or whole tissue samples. More cases of MYC protein overexpression observed compared to MYC translocation. CONCLUSION: Relatively lower frequency of GCB tumours and low gene rearrangement rates were observed in Malaysian population. A national study is therefore warranted to know better the immunogenotypic characteristics of DLBCL in Malaysia and their implications on the survival.

Extranodal NK/T-cell lymphoma mimicking Crohn's colitis.

INTRODUCTION: Extranodal NK/T cell lymphoma is a rare tumour, typically involving the upper aerodigestive tract. Even rarer is primary extranasal disease involving the skin, testis, soft tissue and gastrointestinal tract. CASE REPORT: We report a case of a 46-year-old Chinese male who presented with six months history of abdominal pain, weight loss and rectal bleeding. Diagnostic colonoscopy revealed multiple aphthous ulcers within the ileo-caecal region and distal transverse colon, separated by normal mucosa, mimicking skip lesions of Crohn's colitis. Computer topography (CT) scan of the abdomen showed multiple circumferential thickenings involving predominantly the right colon. A clinical diagnosis of colonic Crohn's disease with possible perforation was made. An extended right hemicolectomy was performed due to uncontrolled rectal bleeding. Histopathology examination of the colon showed infiltration by malignant lymphoid cells associated with necrosis, angiocentricity and angiodestruction. Immunohistochemical studies confirmed T-cell monoclonality, presence of cytotoxic granules and Epstein-Barr virus (EBV) infection. A diagnosis of extranodal NK/T cell lymphoma of the colon was made. DISCUSSION: These findings highlight that colonic NK/T cell lymphoma may clinically mimic other benign inflammatory lesions and should be one of the differential diagnoses in patients presenting with gastrointestinal lesions. The final diagnosis is only possible with appropriate histological and immunohistochemical studies.

Diffuse large B-cell lymphoma of the small intestine in a patient with refractory coeliac disease.

INTRODUCTION: Coeliac disease enteropathy is associated with an increased risk of lymphomas. Enteropathy-associated T-cell lymphoma is the principal malignancy related to coeliac disease. However, studies have shown that other types of lymphoma such as diffuse large B-cell lymphoma may also be associated with coeliac disease. CASE REPORT: We report a 54-year-old Caucasian man who presented with chronic diarrhoea and weight loss. He was diagnosed with coeliac disease based on positive serology results and duodenal, jejunal, and ileal biopsies that showed villous atrophy. Despite adherence to a gluten-free diet, there was no clinical remission and enteropathy-associated T cell lymphoma was suspected. Repeated endoscopic biopsy showed persistent mucosal disease but no evidence of lymphoma. Several weeks later he presented with a perforated jejunum. Histology of the resected jejunum showed diffuse infiltration of submucosa and muscularis propria by malignant lymphoid cells sparing the mucosa. The cells expressed CD20, CD79α, CD10 and BCL6 and ki67 of 80%, consistent with diffuse large B-cell lymphoma. DISCUSSION: It is suspected that the undetected lymphoma may have contributed to the persistent malabsorption syndrome rendering the patient unresponsive to treatment. Despite thorough clinical and endoscopic evaluation and multiple biopsies, histologic diagnosis of DLBCL was only confirmed following resection of the perforated jejunum.

Primary follicular lymphoma of the pancreas: A rare tumour mimicking pancreatic carcinoma.

INTRODUCTION: Primary pancreatic lymphomas are extremely rare. Clinically, primary pancreatic lymphoma mimics symptoms of carcinoma of the pancreatic head. Clinical and radiological features may overlap with other pancreatic conditions such as carcinoma, neuroendocrine tumours and autoimmune pancreatitis. CASE REPORT: We report a case of a 75-year-old man who presented with symptoms of obstructive jaundice. Ultrasonography and computed tomography (CT) showed an ill-defined lobulated soft tissue lesion at the head/uncinate process of the pancreas measuring 4.5 x 4.9 x 5.8 cm. The patient underwent pancreaticoduodenectomy for suspected pancreatic head/uncinate process carcinoma. Histopathology and immunohistochemical assessment of the pancreatic lesion established the diagnosis of a low-grade follicular lymphoma. DISCUSSION: Clinical and imaging features of primary pancreatic lymphoma may often overlap with pancreatic carcinoma. There is a value of obtaining preoperative tissue diagnosis such as tissue biopsy and fine needle aspiration (FNA) cytology with or without flow cytometry to make an accurate diagnosis of non-Hodgkin lymphoma and alleviate the need of more radical surgery in pancreatic lymphoma.

Intraoperative frozen section sentinel lymph node assessment in breast cancer: A tertiary institution experience.

INTRODUCTION: Intraoperative frozen section lymph node assessment helps to predict axillary lymph node metastasis in breast cancer. However, the accuracy of this frozen section analysis may vary among institutions. This study describes our institution's experience in intraoperative analysis of sentinel lymph node and aims to determine the accuracy, sensitivity and specificity of our assessment. MATERIALS AND METHODS: We retrospectively analysed the histopathological material and data from 82 breast cancer patients diagnosed over a period of four years who underwent intraoperative frozen section evaluation of sentinel lymph nodes. RESULTS: Frozen section analysis detected metastasis in 13 out of 82 cases and definitive pathological examination on the paraffin section confirmed these positive findings. There was no false positive case (specificity of 100%). The true positive cases comprised seven macrometastases, five micrometastases and one isolated tumour cells. Sampling error was noted in two cases in which the malignant cells were only present in the deeper final paraffin sections (false negative rate of 13.3%). The test sensitivity was 86.7% and the accuracy rate was 97.5%. These findings are comparable to other published data. CONCLUSION: Intraoperative frozen section analysis is a safe and reliable method for assessment of sentinel lymph node. Knowledge on limitation of frozen section analysis with diligent evaluation of frozen section specimen will be beneficial in reducing interpretation error.

POEMS syndrome.

POEMS syndrome is the syndrome of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and typical Skin changes. A 65-year-old lady presented with the 2-day-history of inability to walk, 4-month-history of progressive worsening of muscle weakness of both lower limbs and 1-year-history of progressive worsening of bilateral numbness of lower limbs. Nerve conduction study revealed generalized sensorimotor demyelinating polyneuropathy. She was initially treated as chronic inflammatory demyelinating polyradiculoneuropathy with intravenous immunoglobulin (IVIG) and high-dose prednisolone. However, she had no significant neurological improvement despite getting standard therapy. In addition to peripheral neuropathy, the presence of hepatosplenomegaly, skin changes, polycythaemia and thrombocytosis prompted for further investigations. She was diagnosed as POEMS syndrome based on the presence of two mandatory major criteria [polyneuropathy, monoclonal plasma cell proliferative disorder (lambda)], one major criterion (sclerotic bone lesions) and three minor criteria (organomegaly, skin changes and thrombocytosis/polycythaemia). She received treatment with melphalan and prednisolone. She achieved clinical improvement and partial response (haematologic and radiological) after six cycles of therapy. We highlight the awareness of this rare syndrome, for patients presenting with peripheral neuropathy and not responding to its standard therapy, by recognizing other associated clinical manifestations and proceeding further diagnostic work-up.

Glypican-3 is useful but not superior to Hep Par 1 in differentiating hepatocellular carcinoma from other liver tumours.

To assess the diagnostic utility of glypican-3 (GPC-3) in comparison to Hep Par 1 in the diagnosis of liver tumours, a cross-sectional study involving 66 resected liver tumours were tested for the protein expression of these markers by immunohistochemistry using monoclonal antibodies. Of the 66 cases, 26 (39.4%) were hepatocellular carcinoma (HCC), 4 (6.1%) were intrahepatic cholangiocarcinoma and 36 (54.5%) were metastatic tumours. Hep Par 1 and GPC-3 expressions in HCC were 24/26 (92.3%) and 19/26 (73.1%) respectively. In contrast, of non-HCC cases, only 2/40 cases (5.0%) expressed Hep Par 1, including a metastatic colorectal adenocarcinoma and a metastatic gastric adenocarcinoma. GPC-3 was expressed in 3/40 cases (7.5%), i.e. a metastatic adenocarcinoma of unknown origin, a metastatic gastric adenocarcinoma and an intrahepatic cholangiocarcinoma. The sensitivity and specificity for Hep Par 1 were 92.3% and 95% respectively while that of GPC-3 was 73.1% and 92.5% respectively. GPC-3 is a useful marker in the diagnosis of HCC. However it is not superior to Hep Par 1 in its sensitivity and specificity. We recommend that it is utilized together with Hep Par 1 as a panel in the diagnosis of HCC.

NK/T cell lymphoma associated with peripheral eosinophilia.

NK/T cell lymphoma, nasal type is an aggressive and uncommon malignancy. Disease that occurs outside of the aerodigestive tract exhibits an even more aggressive clinical behaviour and does not respond as well to conventional therapy compared to its nasal counterpart. We report such a case of NK/T cell lymphoma, nasal type, that presented as an anterior chest wall mass, arising from the left pectoralis muscle. An interesting feature we wish to highlight is the associated eosinophilia that corresponded to disease activity, exhibiting fluctuations with surgical resection and chemotherapy. To the best of our knowledge this is the third reported case of NK/T cell lymphoma that is associated with peripheral eosinophilia. Our case highlights the role of certain NK cell subsets that play a major role in eosinophilic activation in NK/T lymphomas and calls for more research into further classification of this disease by virtue of its NK cell subsets.

Keratoacanthoma: an unusual nasal mass.

We report a case of keratoacanthoma in a non-sun-exposed nasal vestibule of an 84-year-old man. He presented with a progressively growing left nasal mass that had been present for 8 months. Examination showed a non-tender protruding mass arising from medial vestibular wall of the left nostril. Histopathology indicated it was a keratoacanthoma. In an elderly patient with a history of a progressively growing mass in the nose, a differential diagnosis of malignancy should be ruled out, and histological conformation is essential. To our knowledge, only a very small number of cases of nasal vestibular keratoacanthoma have been reported.

Churg-Strauss syndrome presenting with conjunctival and eyelid masses: a case report.

Churg-Strauss syndrome, a small and medium vessel vasculitis, was first described by Churg and Strauss in 1951. It is characterised by the presence of asthma, prominent tissue and blood eosinophilia, systemic vasculitis, and pulmonary and systemic necrotising allergic granulomas. Involvement of the skin, heart and gastrointestinal tract is well documented, but ocular presentation is unusual. We describe a 40-year-old lady who presented with recurrent upper eyelid swelling due to conjunctival lesions. Although she has chronic asthma, Churg-Strauss syndrome was never suspected. The diagnosis of Churg-Strauss syndrome was only made following histological examination of the conjunctival lesions.

Selective loss of B-cell phenotype in lymphocyte predominant Hodgkin lymphoma.

The neoplastic Reed-Sternberg cells characteristic of classical Hodgkin's lymphoma (cHL) are of B-cell origin but they almost always show striking loss of a range of B-cell-associated molecules. In contrast, the neoplastic cells found in lymphocyte predominant Hodgkin's lymphoma (LPHL) (L&H cells) are traditionally thought of as possessing the full repertoire of features associated with germinal centre B cells (eg BCL-6 expression, 'ongoing' Ig gene mutation). In the present paper, we report an extensive phenotypic analysis of L&H cells which revealed down-regulation of a number of markers associated with the B-cell lineage (eg CD19, CD37) and with the germinal centre maturation stage (eg PAG, LCK). The promoter methylation status of three of these down-regulated genes (CD10, CD19, and LCK) was further studied in microdissected L&H cells, and this revealed that their promoters were unmethylated. In contrast, these genes showed promoter methylation in cell lines derived from CHL. Further investigation of the mechanisms responsible for the deregulation of these molecules in L&H cells may provide new insights into the genetic abnormalities underlying LPHL.

Jaw1/LRMP, a germinal centre-associated marker for the immunohistological study of B-cell lymphomas.

Jaw1, also known as lymphoid-restricted membrane protein (LRMP), is an endoplasmic reticulum-associated protein. High levels of Jaw1/LRMP mRNA have been found in germinal centre B-cells and in diffuse large B-cell lymphomas of 'germinal centre' subtype. This paper documents Jaw1/LRMP expression at the protein level in human tissues by immunohistochemical and western blotting analysis using an antibody reactive with paraffin-embedded tissues. Jaw1/LRMP was highly expressed in germinal centre B-cells (in keeping with gene expression data), in 'monocytoid B-cells', and in splenic marginal zone B-cells. It was absent, or present at only low levels, in mature T-cells, although cortical thymocytes were weakly positive. Among lymphoid neoplasms, Jaw1/LRMP was found in germinal centre-derived lymphomas (follicle centre lymphoma, Burkitt's lymphoma, lymphocyte-predominant Hodgkin's disease) but not in T-cell neoplasms (with the exception of a single T lymphoblastic lymphoma). Classical Hodgkin's disease and myeloma lacked Jaw1/LRMP but many cases of chronic lymphocytic leukaemia (but not mantle zone lymphoma) were Jaw1/LRMP-positive. Approximately half of the marginal zone lymphomas were Jaw1/LRMP-positive. In diffuse large B-cell lymphomas, Jaw1/LRMP was found in three-quarters (24/32) of the cases classified phenotypically as being of 'germinal centre' type, but it was also expressed in almost half (13/28) of the 'non-germinal centre' cases. A similar proportion of 'non-germinal centre' cases were positive for the protein products of two other genes expressed highly in germinal centre cells (HGAL/GCET2 and PAG). The fact that all three of these proteins are expressed in a significant proportion of diffuse large B-cell lymphomas assigned to the 'non-germinal centre' category indicates that the immunophenotypic categorization of diffuse large B-cell lymphoma according to cellular origin may be more complicated than currently understood. Finally, the expression of Jaw1/LRMP in other types of lymphoma and in non-lymphoid tissues/tumours may be of interest in differential diagnosis and research.

Loss of CD19 expression in B-cell neoplasms.

AIMS: To investigate whether an antibody against an intracellular epitope can detect CD19 in routine biopsy specimens and thus to document in detail its expression in human lymphomas. METHOD AND RESULTS: A polyclonal antibody to the C terminus of CD19 was used to immunostain paraffin-embedded samples of normal and neoplastic lymphoid tissues. CD19 was widely expressed in normal B cells and in extramedullary plasma cells. It was found in most B-cell neoplasms, but expression in follicular lymphoma was weak (33/69) or negative (four cases). Similarly, CD19 expression in diffuse large B-cell lymphomas was weak (28/56) or negative (eight cases). In T-cell-rich B-cell lymphomas, CD19 was also weak (4/10) or negative (three cases). CD19 was often absent in post-transplant B lymphoproliferative disease, classical Hodgkin's disease and plasma cell neoplasms. An unexpected finding was the frequent absence of CD19 in the neoplastic cells in lymphocyte predominant Hodgkin's disease. CONCLUSIONS: CD19 can now be detected in routine biopsy specimens. In contrast to the classical pan-B marker CD20, CD19 is not always strongly expressed in B-cell neoplasms. Furthermore, the lymphocytic and histiocytic (L&H) cells of lymphocyte predominant Hodgkin's disease (which express most B-cell-associated markers) commonly lack CD19.

Signet-ring Cell Lymphoma-a Case Report.

A case of signet-ring cell lymphoma diagnosed initially by fine needle aspiration cytology is reported. This rare tumor is a variant of follicular lymphoma, which closely resembles metastatic adenocarcinoma and other tumors which exhibit signet-ring cell appearance. Correct diagnosis can be achieved by careful morphologic analysis together with positive reactivity with lymphoid markers. The cytohistologic, immunohistochemical and electron microscopic features are described, and the differ ential diagnostic considerations are discussed in the report.

A cervical ectopic masquerading as a molar pregnancy.

We report a case of cervical pregnancy complicated by life threatening hemorrhage. An initial diagnosis of molar pregnancy was made preoperatively. During uterine evacuation she developed profuse hemorrhage which required an emergency hysterectomy for uncontrolled bleeding. Histopathological examination confirmed a cervical pregnancy. The clinical and pathological criteria for the diagnosis and the etiology of cervical pregnancy are discussed.

The triad of lichen planus, thymoma and liver cirrhosis-hepatoma. First reported case.

We describe a patient with liver cirrhosis who presented with erosive oral and cutaneous lichen planus (LP) and incidentally was found simultaneously to have thymoma and hepatoma. We support the notion forwarded earlier that LP and chronic liver disease is more than a mere coincidence and that there is a non-coincidental association between LP and thymoma. We believe this is also the first reported case in the English Literature of coexistence of the three condition LP, thymoma and hepatoma complicating liver disease.

Osteosarcoma in a sixteen-month old boy.

We report a case of a sixteen-month old boy with osteosarcoma of the left humerus. To the best of our knowledge this is the youngest case reported in Malaysia. This case illustrates that osteosarcoma although rare does occur in a very young child. The child died six weeks after presentation due to disseminated disease.