Alexander C. L. Chan

Natural killer cell lymphoma/leukemia: pathology and treatment

Malignancies arising from cells of putative natural killer (NK) cell origin have increasingly been recognized as distinct clinicopathological entities. These malignancies are marked by tumour cells with NK cell characteristics, including the immunophenotype of CD2+, surface CD3−, cytoplasmic CD3ϵ+, CD7±, and CD56+, and the genotype of germline T cell receptor gene. A consistent association with monoclonal Epstein–Barr virus infection in the tumour cell has been observed. These tumours are now regarded as putative NK cell lymphoma/leukemia. Pathologically, tumour cells show variable cytological appearances, with frequent angiocentricity and angioinvasion, associated with zonal necrosis. Clinically, most cases occur in the nasal area and upper aerodigestive tract. However, occurrence in non‐nasal sites such as the skin, gastrointestinal tract and testis is also observed. A particularly aggressive form of NK lymphoma/leukemia presents fulminantly as disseminated disease sometimes with a leukemic phase. All types of NK lymphoma/leukemia have an extremely poor prognosis with a median survival of less than a year. New modalities of treatment, including the use of high dose chemotherapy and stem cell rescue may be needed to improve treatment outcome.

Primary cardiac lymphoma

Primary cardiac lymphoma is a rare entity. We report on the clinicopathological features of 2 patients with primary cardiac lymphomas: one involving the right atrium resulting in intractable right heart failure, and the other involving the pericardium with massive pericardial effusion. In the first patient, sternotomy and surgical biopsy of the tumor were performed to arrive at the diagnosis. In the second patient, CT thorax and transesophageal echocardiography helped to diagnose the pericardial tumor, and cytological examination of the pericardial fluid established the pathological diagnosis of lymphoma. Combination chemotherapy (COPP) was started in both patients. The first patient died on the first day of chemotherapy due to intractable heart failure, while the second attained a partial response to chemotherapy but died of progressive disease 8 weeks later. This is followed by a literature review of 21 patients with primary cardiac lymphoma. In conclusion, the prognosis of primary cardiac tumor remains poor. Am. J. Hematol. 54:79–83, 1997

Expression of p53 and its relationship with human papillomavirus in penile carcinomas.

We studied p53 over-expression in a series of 42 primary penile carcinomas (seven verrucous carcinomas, 14 well-differentiated, 15 moderately-differentiated and six poorly-differentiated squamous cell carcinomas) from Chinese patients using the p53 protein specific mouse monoclonal antibody DO-7 on paraffin sections. p53 protein was detected in 40% (17 cases) of the tumours. The p53 staining was not observed in the penile warts (n = 6) and verrucous carcinomas (n = 7). Positive p53 staining was identified only in the less differentiated tumour cells in the periphery of the tumour cell nests in all the cases. The non-invasive dysplastic epithelium next to the tumours could also be positive for p53 protein (three out of 10 cases in which the dysplastic epithelium adjacent to the tumour was adequately sampled). Furthermore, 100% of the human papillomavirus (HPV)-positive cases showed positive p53 staining. It is concluded that p53 over-expression is present in penile squamous cell carcinomas and adjacent non-invasive tumour cells. An inverse correlation between HPV and p53 gene mutation is not observed in penile cancers.

Near Tetraploidy in Three Cases of Acute Myeloid Leukemia Associated with Mediastinal Granulocytic Sarcoma

Granulocytic sarcoma (GS) is a rare manifestation of acute myeloid leukemia (AML), blastic transformation of chronic myeloid leukemia, and the myelodysplastic syndromes. The mediastinum is an unusual site of presentation. We report a series of three female patients with mediastinal GS. They were characterized by the presence of large and bizarre blast cells and near tetraploidy on cytogenetic analysis. All three patients responded poorly to chemotherapy. Near tetraploid AML is a rare entity, usually present in male patients, and has not been associated with GS. The clinical and pathological similarities in these three cases suggest a distinct category of poor-risk AML for which more intensive treatment is needed.

Giant adrenal lipoma : A report of two cases and review of literature

Lipoma of the adrenal gland is extremely rare. We report two cases of adrenal lipomas, one in a 64-year-old female and the other a 78-year-old male. The sizes of these tumours (4.5 cm and 8 cm) were larger than those reported in the literature. Both cases were found incidentally, one at autopsy and the other during ultrasonographic examination for unrelated condition. The histogenesis, clinicopathological features, differential diagnosis and management of these cases are discussed.

Mantle cell lymphoma in the Chinese: Clinicopathological features and treatment outcome

We report the clinical, molecular, and immunohistological findings of 20 Chinese patients with mantle cell lymphoma diagnosed over a 10‐year period. The disease affected mainly elderly patients (median age, 65.5 years) with a male predominance (M/F, 3/1). Eighty percent presented with advanced stage III/IV disease but only 25% had B symptoms. Eighty‐five percent had extranodal disease at presentation. Complete remission (CR) and partial remission (PR) were achieved in 45% and 40% of the patients, respectively. There was no difference in the CR rate for patients treated with anthracycline‐containing or nonanthracycline‐containing regimens (43% and 50%, P = 0.67). Disease progression or relapse was observed after a median of 26 months in patients who initially responded to treatment. Extranodal relapse occurred in the central nervous system (n = 1), bone marrow (n = 1), pleura (n = 2), orbit (n = 2), and the gastrointestinal tract (n = 3). The median overall survival (OS) was 52 months but there were no long‐term survivors. This was not different from the median OS of 53 months of patients with diffuse large cell (DLC) lymphoma treated in the same center over the same period (log rank, P = 0.76). Of the 12 patients who were tested for bcl‐1 rearrangement by polymerase chain reaction (PCR), five (42%) were positive for rearrangement in the major translocation cluster (MTC) region. The median OS rates were 45 months and 63 months for PCR positive and negative patients, respectively (P = 0.97). In conclusion, MCL is a disease mainly of the elderly in the Chinese with a male predominance and most had advanced‐stage disease and extranodal involvement at presentation. Clinicopathologic features and treatment outcome were similar to Caucasian patients, in that the disease combined the aggressive nature of DLC lymphoma and the incurability of low‐grade lymphoma. Am. J. Hematol. 59:295–301, 1998.

Granulocytic sarcoma of megakaryoblastic differentiation complicating chronic idiopathic myelofibrosis

We report the development of soft tissue granulocytic sarcoma with megakaryoblastic differentiation in a patient with chronic idiopathic myelofibrosis, which has hitherto been undescribed. Although an artifactual signet ring appearance of the blasts was found in the formalin-fixed tissue and caused diagnostic problems, the histological appearance on B-5 fixed material and immunophenotyping confirmed the diagnosis. Cytogenetic analysis showed 47,XY,+der(1)del(1)(?p13) at initial presentation and 47,XY,del(1)(?13),+der(1)del(1)(?p13) at the time of soft tissue blastic transformation, indicating that partial trisomy 1 might be of pathogenetic significance.

Primary B cell lymphoma of the mediastinum

Primary B cell mediastinal lymphoma has been recognized as a distinct entity recently. This is a retrospective study to define the clinical features and treatment outcome over a 10‐year period. Twenty‐four consecutive patients (male/female: 11/13) with B cell lymphoma primarily involving the mediastinum were studied. The median age was 34 years. Symptoms were mainly referrable to the chest, with superior vena cava syndrome (SVCO) present in one‐third of the patients. Bulky disease was present in over half (58 per cent) and B symptoms were present in 38 per cent of patients. The overall CR rate was 70 per cent and the 5‐year OS rates were 56 per cent and 72 per cent for all and CR patients respectively. Five (71 per cent) primary refractory patients and four (66 per cent) relapsed patients died despite salvage therapy. Six relapses occurred at a median of 6 months from treatment. This study showed that primary large B cell lymphoma of the mediastinum is a clinically distinct entity affecting young patients. A significant proportion attained CR and overall, more than half achieved prolonged remission, and most of the relapses occurred early. However, those who failed to attain CR or relapsed still had a poor outcome. An intensive therapy such as autologous bone marrow transplant has to be considered in this subgroup of patients.

Isolated lymph node T lymphoblastic transformation of chronic myeloid leukemia during interferon treatment.

Isolated nodal T lymphoblastic transformation of chronic myeloid leukemia (CML) with the marrow still in chronic phase is rare. A case of CML treated by α‐interferon developed this unusual complication. However, after successful treatment of the blastic transformation, the patient remained responsive to interferon and maintained a major cytogenetic response for over 2 years. This case illustrated a rare clinical progression of CML on interferon treatment to isolated nodal T lymphoblastic transformation. This unusual form of blastic transformation may have a better prognosis than other forms of blastic crisis. Am. J. Hematol. 62:256–258, 1999.

Absence of Epstein-Barr virus in penile carcinoma. A study of 42 cases using in situ hybridization.

Background. The relationship between Epstein–Barr virus (EBV) and carcinomas of the lower female genital tract has been the focus of some studies in recent years. However, the association between EBV and penile carcinoma never has been investigated. The aim of this study was to identify the possible role of EBV in penile carcinoma of Chinese patients.