Fulminant hepatic failure in non-Hodgkin lymphoma patients treated with chemotherapy.

Chemotherapy is the mainstay of therapy for patients with non-Hodgkin lymphoma. Among side-effects associated with the use of chemotherapy, immunosuppression is one which can be potentially fatal. In hepatitis B carriers, immunosuppression permits widespread infection of the hepatocytes and its subsequent withdrawal causes an "immunological rebound" leading to massive necrosis of hepatocytes. 4 patients who died of fulminant hepatitis following chemotherapy are reported. These were patients with positive hepatitis B serology. Caution is advised when treating non-Hodgkin lymphoma in patients from hepatitis B endemic regions.

Diagnostic sensitivity of polymerase chain reaction and Southern blot hybridization for the detection of human papillomavirus DNA in biopsy specimens from cervical lesions.

Human papillomaviruses (HPVs) are associated with benign and malignant neoplasms of the cervix. One of the criteria for their etiologic role requires an assessment of whether virtually all or only a small fraction of lesions contain viral genomes. DNA preparations from colposcopically directed punch biopsies of cervical lesions were analyzed by Southern blot hybridization and the polymerase chain reaction (PCR) for the presence of HPV DNA. The biopsy specimens represented different pathologic entities (koilocytosis, condyloma, cervical intraepithelial neoplasia, and invasive carcinoma). In Southern blot hybridization with radioactive probes for HPV 11, 16, 18, 31, and 33, HPV DNA was detected in 74% of the biopsy specimens (42 of 57 cases), with the predominant types being HPV 16 and HPV 18. In contrast, after PCR amplification with primers yielding fragments of characteristic size for HPV 11, 16, and 18, the analysis of the same 57 biopsy specimens revealed that all samples were positive for at least one HPV type. To exclude false-positive PCR results, controls without HPV DNA were interspersed at regular intervals, and results were evaluated only if these controls remained HPV negative. To exclude false-negative results due to failure of the reaction, a target sequence within the c-Ha-ras-1 gene was used as an internal control. All HPV typing results obtained by Southern blot hybridization were in agreement with HPV typing by PCR. The higher number of positive samples in the latter analysis stems from the increased sensitivity of PCR, which was which was effective in identifying as few as 10-100 HPV DNA molecules; in contrast, the sensitivity of Southern blot hybridization was 1 pg, or approximately 10(5) molecules of HPV DNA. The authors conclude that, with sufficiently sensitive diagnostic methods, HPV DNA can be detected in most, if not all, neoplastic cervical lesions.

Male breast cancer: a retrospective study with immunohistochemical analysis of hormone receptor expression.

Of twenty-two cases of breast carcinoma diagnosed in men in Singapore since 1969, 17 were classified as infiltrative ductal carcinoma, three as papillary and one as mucinous carcinoma. The remaining case could not be classified and further immunohistochemical workup suggested the possibility of metastasis from an occult prostatic primary. Fourteen cases that were staged revealed a majority of seven (50%) cases in Stage II, with three (21%) Stage I, one (8%) Stage III and three (21%) Stage IV cases. Estrogen and progesterone receptor (ER and PR) expression was determined in 20 cases using immunohistochemical staining of archival paraffin embedded tissue blocks, which demonstrated ER and PR positivity in 65% of the cases respectively.

Human papillomavirus in dysplasia and carcinoma of the cervix in Singapore.

A prospective study was conducted in Singapore in 1985 where 107 women with abnormal cervical smears were studied for cervical neoplasia and its association with the human papillomaviruses (HPV), using HPV 11, 16 and 18 DNA as probes. Cervical biopsies were performed for histology as well as for DNA Southern Blot hybridization studies to detect the presence of HPV 11, 16 or 18 genome. The prevalence of the various types of papillomavirus DNA in cervical tissue samples from cervical carcinoma and dysplasias is presented. HPV types 16 and 18 were found in 5 of 8 (63%) cases of invasive squamous cell carcinoma (SCC), in 12 of 41 (29%) cases of squamous carcinoma-in-situ (CIN 3) and in 3 of 48 (6%) cases of lower grade dysplasia. None of our cases of SCC were associated with unknown HPV types detected using a mixture of HPV 16 or 18 DNA under conditions of low stringency. These unknown HPV types were present in approximately one quarter of our cases of dysplasia of all grades.

MACOP-B in advanced non-Hodgkin's lymphoma.

Between May 1986 and March 1991, 38 patients with previously untreated advanced intermediate and high-grade non-Hodgkin's lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B): 73% of the patients had stages III and IV disease, 55% had "B" symptoms, and 55% had bulky disease (nodal masses > 10 cm). Histologic subtypes included diffuse large-cell and immunoblastic lymphoma. In 96% of patients clinical response was achieved (69% complete response and 27% partial response). Acturial disease-free survival and overall survival were 55% and 60%, respectively, at 2 years. Treatment-related mortality was 16%: 3 patients died from neutropenic sepsis and 3 (hepatitis B carriers) from fulminant hepatitis at the time of steroid withdrawal. The incidence of nonfatal neutropenic fever was 24% and mucocutaneous toxicity was common. The poorer overall results may be attributed to more advanced disease. Caution is advised in the use of MACOP-B among hepatitis B carriers.

Evidence of HTLV-I infection in Singapore prostitutes.

Sera obtained in 1987 from 63 male and 632 female Singapore prostitutes were screened for antibody to human T-cell leukaemia virus (HTLV)-I with a particle agglutination test. Of the 3 males and 4 females who were positive one had antibody to HTLV-I core and envelope antigen on Western Blot. Two subjects had presumptive antibody to HTLV-I core antigen and a third subject had such antibody on a repeat specimen in 1989. These sera were negative for HIV-1 antibody. There is evidence of infection with HTLV-I or a variant virus in this population. The infection is likely to have been sexually transmitted.

Palatine tonsillar metastasis from carcinoma of the colon.

Metastatic carcinoma of the palatine tonsil is rare, with only 92 cases reported in the world literature. We report a case of tonsillar metastasis from the colon. This is an unusual case not only because it is the first case report of tonsillar metastasis from this site but also because the tonsillar secondary is the first sign of the primary disease.

View from beneath: pathology in focus. Synovial sarcoma of hypopharynx.

Synovial sarcoma of the hypopharynx is a rare neoplasm. To date only 23 cases of synovial sarcoma of the hypopharynx have been reported in the literature. An additional case in an 18-year-old male is presented. This is the first case of synovial sarcoma in the hypopharynx to be reported in Singapore. The presentation was that of a mass in the hypopharynx; progressive dysphagia, intermittent hoarseness and gradual airway compromise. A CT scan was valuable in determining the site of origin and extent of the lesion. Histopathology was diagnostic. Treatment comprised of wide surgical excision of the tumour and post-operative radiotherapy.

The non-Hodgkin's lymphomas.

This paper is a review of the pathology of non-Hodgkin's lymphomas. The various classifications proposed as alternatives to the Rappaport classification are briefly reviewed. The light microscopic morphology of the various sub-types are described, mentioning where possible the derivation of the tumour cell type as delineated by enzyme and immunological cell marker studies. The natural history and salient clinicopathological aspects of the disease entities are also described.

Breast lymphoma--a pathologic study of 14 cases.

Fourteen cases of malignant non-Hodgkin's lymphoma of the breast were diagnosed at the Department of Pathology, Singapore General Hospital, since 1988. All were females with an age range of 30 to 69 years. Twelve cases were B cell and 2 were T cell in immunophenotype. Of the B cell lymphomas, one was subtyped as follicular, 8 diffuse large cell (IWF) or centroblastic (Kiel) and 3 immunoblastic lymphomas. Both T cell tumours were Ki-1 positive, large cell anaplastic lymphomas. Malignant lymphoma was not clinically suspected in any patient at presentation. Histologically, 3 cases were initially diagnosed as carcinomas, one on a trucut biopsy, another during frozen section evaluation and the third was a breast excision specimen. The pathological characteristics and potential histologic problems are detailed. The rarity of the disease, lack of uniform classification and variable treatment modalities make prognostic predictions of breast lymphoma difficult.

Malignant histiocytosis --- a case report.

Malignant Histiocytosis (MH) is an uncommon disorder characterised by systemic tissue infiltration of atypical histiocytes and its precursors. The clinical features included fever with weight loss, hepatosplenomegaly and pancytopenia. The antemortem pathology of the lymph node and bone marrow were non-specific and non-diagnostic. However, at autopsy, there were florid pathological changes of malignant histiocytosis. This case illustrates the difficulty of making a definite antemortem diagnosis of this rare malignant condition and the terminology, aetiology and pathological features are discussed.

Percutaneous aspiration lung biopsy.

Percutaneous needle aspiration lung biopsy is reviewed. Its method and place in the investigation of lung lesions is described and re-emphasized. It is a safe, cheap, quick and simple way to achieve a definitive diagnosis. The diagnostic accuracy is high and the complication rate low. The paper strongly advocates wider usage of this very useful investigative modality.

Sudden postoperative death from ruptured intracranial vascular malformations in a patient receiving total parenteral nutrition.

A 30-year-old female patient underwent oesophagectomy and colonic transposition for multiple oesophageal strictures associated with epidermolysis bullosa dystrophica. On the 9th postoperative day, she had convulsions and died, whilst in a state of severe hyperglycaemia, which was presumably iatrogenically induced by total parenteral nutrition. Autopsy and subsequent histological examination revealed that the cause of death was acute subarachnoid haemorrhage from ruptured, intracranial cryptic arteriovenous malformations. Postmortem vitreous biochemistry confirmed that death had occurred in a state of hyperglycaemia. The pathology of intracranial vascular malformations and the medico-legal implications of this case are discussed.

Primary pulmonary lymphoma: report of three cases and a brief review of the literature.

We report three patients with primary pulmonary non-Hodgkin's lymphoma which is a rare extranodal lymphoid neoplasm. In these patients, both the history and physical findings were vague and minimal. The laboratory findings were normal apart from chest radiographic abnormalities and serum gammopathy in two cases. All three patients underwent several diagnostic procedures before conclusive results were obtained from thoracotomy specimens. Histology revealed small lymphocytic infiltrate of the pulmonary parenchyma with nodal involvement in all three cases. All three patients had surgical resection and two received adjuvant chemotherapy. They are all alive and symptom-free at 92, 51 and 12 months, respectively, after diagnosis.

Oestrogen receptors in well differentiated thyroid cancers.

Oestrogen receptor (ER) monoclonal antibody, H222 was used to study ER expression in forty-seven paraffin embedded blocks of well differentiated thyroid cancers. Trypsinisation, DNase I digestion, together with the use of labelled streptavidin biotin immuno-histochemical staining kit were adopted to increase the sensitivity of the immunoreaction. One out of twenty-seven papillary carcinomas and one out of twenty follicular carcinomas were immunoreactive. Thus, 4.3% of the well differentiated thyroid cancers were noted to express ER. The increased incidence and the better prognosis in females with well differentiated thyroid cancers is unlikely to be explained on the presence or absence of ER.

Disseminated histiocytosis X with diabetes insipidus and diabetes mellitus in an adult female (histiocytosis with DI and DM).

We report the clinical presentations and pathologic findings in an adult female who had Disseminated Histiocytosis X associated with diabetes insipidus and diabetes mellitus. The association of these three conditions in the same subject is rare. The current knowledge on Disseminated Histiocytosis X is reviewed and the possible relationship between these three conditions discussed.

Reversal of red cell aplasia and marrow fibrosis in non-Hodgkin's lymphoma.

Red cell aplasia and marrow fibrosis occurred in a 34-year-old man with diffuse well differentiated lymphocytic lymphoma. Complete recovery of marrow function and histology with remission of the lymphoproliferative malignancy were observed following 6 courses of combination chemotherapy.

Malignant histiocytosis--a clinicopathologic study of 5 cases.

The clinico-pathological features of 5 patients with malignant histiocytosis aged 18 years to 73 years seen over a three year period from 1980 to 1983 at the Department of Haematology Singapore General Hospital were studied. Haematological, cytological and histopathological findings of the disease are described. Diagnosis of malignant histiocytosis was established from biopsies of bone marrow, liver, spleen or lymph nodes. Three out of the 5 patients died rapidly after diagnosis despite cytotoxic chemotherapy. One patient was lost to follow up while another is alive surviving so far for 3 months since diagnosis. The differential diagnosis of malignant histiocytosis is also discussed.

The role of the fibreoptic bronchoscope in the diagnosis of bronchial neoplasm.

We report our experience from January 1980 to December 1985 with the fibreoptic bronchoscope in the evaluation of bronchial disease, particularly bronchial neoplasm. Bronchoscopy was performed in 456 patients (329 men, 127 women) and the pathological results were analysed retrospectively. The main indications for bronchoscopy were the radiological findings of a central mass (22%), a peripheral mass (18%), lobar or segmental collapse (14%), unresolved pneumonia (13%), and haemoptysis as a symptom (15%). Abnormal bronchoscopic findings were noted in 167 patients. This was supported by histological examination in 136 patients (81%). In 43 patients (32%) the diagnosis was only made on cytology. The clinical predictive values of common indications were: central mass 0.53, lobar or segmental collapse 0.51, and superior vena cava obstruction 0.36. The fibreoptic bronchoscope is a highly efficient method for diagnosing bronchial malignancy. Bronchial brushing and aspiration should be performed in all cases to maximise the yield.

Difficulty of obtaining wide tumour to deep fascial margins in Asian women with breast cancers: implications on treatment and prognosis.

This prospective study sought to determine the width of tumour to fascial margins attainable after mastectomy in Asian women with breast cancers. The narrowest perpendicular distance from tumour to the deep fascia was measured in the mastectomy specimens of 177 consecutive Singaporean women with primary breast carcinomas. A highly significant linear correlation was present between the tumour size (P < 0.001, Pearson's R = -0.34) and the width of deep margins. Furthermore, T staging (P < 0.01, ANOVA) was inversely correlated with the width of deep margins and significant differences were observed between early (T0 to T2) and late (T3 to T4) lesions. In patients with ductal carcinoma in situ (DCIS) and T1 lesions, deep margins greater than 10 mm were achieved in only 23% and 33% of the women respectively. For patients with DCIS, 33% had either positive margins or margins less than 2 mm. The corresponding figures for women with T1 and T2 lesions were 11% and 26%, respectively. The inability to obtain negative deep margins were considerable with large tumours as 10% of the women with T3 tumours and 33% with T4 tumours had positive margins. Thus the proportion of positive or narrow deep margins following mastectomy is appreciable in Asian women and even in those with early tumours. The implications of these findings on the risk of locoregional recurrence or the need for more radical surgery or adjuvant radiotherapy remain uncertain, and will require further elucidation.