Challenging and unusual cases: Case 4. Malignant mesothelioma presenting as an anterior mediastinal mass.
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Biomedical subjects
Publications and source records attributed to E J Wills.
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Two unrelated coatimundi (Nasua nasua) had bilaterally enlarged adrenal glands at necropsy, and sections of the glands from both animals had histopathological features consistent with neoplasia. They were differentiated from an adrenal cortical tumour on the basis of their light microscopical morphology, immunoperoxidase staining and electron microscopic studies and a final diagnosis of phaeochromocytoma was made. To the authors' knowledge, these are the first reported cases of phaeochromocytoma in coatimundi.
Hyalinising spindle cell tumour with giant rosettes (HSCTGR) is an uncommon, recently described low-grade sarcoma which shares many histological features with low-grade fibromyxoid sarcoma (LGFMS). We report a case of HSCTGR occurring in the deep soft tissues of the thigh of a 46-year-old woman, that presented as a slowly growing, painless mass. Microscopically the tumour was composed of spindled stromal cells amongst which were scattered so-called collagen rosettes. The distinctive feature of this case was the previously unreported finding of lymphoid cells of T-cell phenotype admixed with fibrohistioctyic cells in the cellular cuff surrounding the collagenous core of the rosettes. The case was further unusual in that it included focal areas of increased cellularity with a mitotic count of up to three per 10 high-power fields. While the latter feature has been associated with increased recurrences and metastases in LGFMS, it is not known whether the significance is similar in HSCTGR. The spindled stromal cells showed ultrastructural features of poorly differentiated fibroblasts, while those at the edges of the rosettes showed features of altered fibroblasts, some with a fibrohistiocytic appearance. These findings support the interpretation that HSCTGR forms part of the spectrum of sarcomas showing fibroblastic differentiation.
HYPOTHESIS: Trends in serum albumin concentration over time provide a better prediction of clinical outcome in CAPD patients than a single mean value. METHODS: This was a retrospective review of outcome at 36 months in 225 adult CAPD patients. Mean serum albumin was determined for the first (SA1) and second (SA2) 6 months of treatment and patients grouped according to SA1 (group I, > 37; group II, 34-37; group III, < 34 g/l) and according to the change in serum albumin (delta SA) between the first and second 6 months (increased/static or decreased). Patient (PS) and technique (TS) survival were determined by Kaplan-Meier survival analysis. The effect of SA1 and delta SA on survival were determined in a multivariate Cox regression analysis model that included age and presence or absence of a systemic disease. RESULTS: By SA1 group, PS and TS survival at 36 months were 94 and 76% (group I), 64 and 53% (group II) and 70 and 52% (group III). If delta SA increased/remained static, then SA1 did not predict PS (group I, 100%; group II, 96%; group III, 74%; P = n.s.) or TS (group I, 72%; group II, 63%; group III, 65%; P = n.s.). If delta SA decreased, PS was worse in groups II and III, both as compared to group I (PS group I, 88%; group II, 52%; group III, 34%; P = 0.02) and as compared to the groups II and III when delta SA increased (PS group II, 74 vs 52%, P = 0.05; group III, 82 vs 34%, P = 0.005) The same trend was seen for TS. In the multivariate Cox regression model, age, direction of change in serum albumin, and presence of a multisystem disease were significant predictors of survival, whereas SA1 was not. CONCLUSION: Early hypoalbuminaemia in CAPD only predicts a worse patient and technique survival if mean serum albumin decreases further from the first to second 6 months of dialysis therapy. Change in serum albumin between the first and second 6 months of CAPD and the mean serum albumin over the first 6 months together offer better discrimination of outcome than either alone.
A patient with acute generalized pustular psoriasis was successfully treated with a combination of oral cyclosporin (6 mg/kg per day) and photochemotherapy (PUVA). Although early inpatient treatment with weak topical steroids and PUVA produced initial improvement, the patient's clinical condition fluctuated, with the subsequent development of erythroderma. The addition of oral cyclosporin produced dramatic improvement within 1 week of its commencement. The patient remained in remission 12 months following cessation of therapy.
OBJECTIVE: To present the earliest Australian case of the acquired immunodeficiency syndrome (AIDS) reported to date. CLINICAL FEATURES: A 72-year-old man developed a prolonged illness, beginning in February 1981, characterised by anorexia, malaise, weight loss and an episode of herpes zoster. In July he noted the insidious onset of dyspnoea with a productive cough. He was admitted to hospital in August, where Pneumocystis carinii pneumonia was diagnosed from a transbronchial lung biopsy. Splenomegaly and generalised lymphadenopathy were noted but a scalene lymph node biopsy examined at that time failed to establish an underlying diagnosis. The patient was single and lived alone in an inner suburb of Sydney. He had never left Australia and had never received a blood transfusion. His sexual history is not recorded, nor is there any documented history of intravenous drug use. OUTCOME: The patient died in September 1981. Recent re-examination of the preserved lymph node specimen by means of an in-situ hybridisation method detected human immunodeficiency virus (HIV). Preserved prostatic tissue from a resection performed in January 1980 on the same patient was also found to be HIV positive. CONCLUSION: AIDS existed in Australia as early as July 1981, around the time of the publication of the first American case reports. Whether this represents an isolated case in a man who progressed rapidly because of his relatively advanced age, or whether HIV was present earlier in Australia than previously thought, remains unanswered.
A new human bladder cancer cell line, UCRU-BL-28 has been established and characterized from a relapsed, cisplatin resistant, grade II, stage T4 tumor. This line is tumorigenic in nude mice and reflects the pathology of the original tumor. The morphology, the expression of tumor-associated antigens and EGF receptors, and the ability to grow both in an anchorage independent manner and in the absence of serum is explored. The BL-28 line has 71-74XXY chromosomes, with del 5q, der(9) and i(19q). Further studies on the molecular basis of bladder cancer, chemosensitivity to cisplatin, growth factor production and tissue invasion are under way.
A rarely encountered but distinctive type of aggressive malignant tumor of childhood and adolescence has been recently described as occurring predominantly or exclusively intrabdominally. It is characterized by a generally diffuse pattern of growth of small cells with hyperchromatic nuclei, scanty cytoplasm, patchy epithelial differentiation, immunohistochemical co-expression of keratin and desmin intermediate filaments and a focal but pronounced desmoplastic stromal component. It is regarded as yet another variant in the group of small round cell tumors (SRCT) of infancy and childhood. This case report of a mass in the greater omentum of a 15 yr-old girl adds to the 33 cases already described in the English literature.
This report describes a patient with a large granular lymphocyte leukaemia (CD8 + lymphoproliferative disease) and severe neutropenia (less than 0.5 x 10(9)/l) in whom exercise resulted in a marked lymphocytosis, a phenomenon which has not previously been recorded. The lymphocyte count at rest was within normal limits (2.2 x 10(9)/l), then fell to the resting level within 15 min of cessation of exercise. The peripheral blood mononuclear cells showed the morphology of large granular lymphocytes (LGL) by light and electron microscopy both at rest (30%) and to a much greater extent during exercise (70%). Immunophenotyping of these lymphocytes during exercise demonstrated that the predominant cell was CD3+, CD8+, CD57+ (Leu7)/CD4-, CD16-, CD25-. In the resting state, despite a total lymphocyte count within the normal range, surface marker studies indicated an excess of cells with the CD8+/CD57 + T cell phenotype (26%; cf. normal range less than or equal to 10%). Functional assays revealed a minimal increase in natural killer (NK) activity during exercise. T cell receptor beta chain gene rearrangement was demonstrable in the peripheral blood at rest and during exercise. Although severe neutropenia was present, the growth of normal colony forming units, granulocyte-macrophage (CFU-GM) was not inhibited by patient lymphocytes and no anti-neutrophil antibodies were demonstrated. Finally, hyposplenism has developed and the relationship of this to the LGL leukaemia is discussed. In summary, the findings demonstrated large granular lymphocyte leukaemia as the primary disorder for which the primary manifestation, apart from the neutropenia, was a marked exercise-induced lymphocytosis.
A xenografted small-cell, undifferentiated prostate (SCUCP) cancer line, UCRU-Pr-2, was implanted at different sites within nude mice to examine the effect of local environmental factors on tumor growth and behavior. All tumors that grew were small-cell carcinomas. Fragments implanted within muscle and under the kidney capsule were locally invasive; however, tumors that grew subcutaneously or intraperitoneally showed no invasion. UCRU-Pr-2 did not grow in the spleen or the liver. No induced metastases were observed in the lung after intravenous injection. The sites of implantation did not allow the outgrowth of subpopulations as detected by the parameters used: light and electron microscopy, expression of tumor markers, levels of hormone production, and DNA flow cytometry. Electron microscopy, which showed both glandular and neuroendocrine differentiation within the same cell, does not support a dual-cell origin of SCUCP.
Ultrastructural features of squamous differentiation have been found in adenocarcinomatous cells in a xenografted line (UCRU-BL-17) established in nude mice from a primary human bladder transitional cell carcinoma (grade III, stage T4) with a tetraploid DNA component. The line has been characterized by light and electron microscopy, flow cytometry and immunocytochemistry. The initial xenograft showed predominantly adenocarcinomatous differentiation with mucin secretion, whilst the subsequent passages also contained cells showing squamous differentiation. A xenograft subline established from a cell culture of the initial xenograft shows the emergence of a population of cells with near triploid DNA, which are less differentiated, grow more quickly, show decreased expression of carcinoembryonic antigen, and a change in the distribution of staining with peanut lectin from cell surface to cytoplasm. These lines offer an unusual opportunity to study the histogenetic relationships between the histological subtypes of bladder cancer.
The first xenograft line of small cell undifferentiated carcinoma of the prostate (UCRU-PR-2) has been established and characterized. The donor tumor and the xenograft share the common morphological and ultrastructural features of small cell undifferentiated carcinoma (including neurosecretory granules) but also elaborate epithelial membrane antigen and carcinoembryonic antigen, in addition to neurone-specific enolase. The line expresses a diploid DNA complement. Androgen and estrogen receptors are not expressed, although prostatic acid phosphatase is present in sera from tumor-bearing mice in low levels. From these studies, we postulate a possible common stem cell origin for adenocarcinoma and small cell undifferentiated carcinoma of the prostate; further studies of a cell line derived from this tumor may clarify the issue.
Five years experience in the application of electron microscopy to fine needle aspiration biopsy specimens is reviewed. In an initial evaluation, 200 consecutive unselected specimens were examined; 89 proved diagnostic and, in a third of these, electron microscopy gave additional information that was often essential to diagnosis. Negative specimens resulted almost entirely from failure to obtain an adequate amount of material. Results were improved by the adoption of a preparation technique involving concentration of the cells in bovine serum albumin and by the inspection of a rapidly stained smear at the time of the aspiration procedure, with a further needle pass for electron microscopy being performed if necessary. Despite the small size of specimens, adequate examination was usually possible and electron microscopy has proved of value in the diagnosis of tumor samples acquired by fine needle aspiration in the same way as has been established with the larger sized specimens obtained by conventional biopsy and surgical resection.
In 1969 it was recognised that tumors with light microscopic appearances indistinguishable from Ewing's sarcoma of bone may arise in extraskeletal sites (extraskeletal Ewing's sarcoma). Here, we review the available literature and report five new cases. All five received combined modality therapy with combination chemotherapy and radiotherapy to the primary site followed by surgical excision in two. All attained complete remission; after a median follow-up of 26 months, three remain disease-free but two have relapsed and died. Our experience, in accord with previous series, suggests that extraskeletal Ewing's sarcoma compared with its bony counterpart tends to occur in older subjects, has a similar incidence in males and females, usually presents with a painless mass and readily responds to combined modality therapy. We detected no light or electron microscopic features to denote a histogenetic origin. However, we suspect extraskeletal Ewing's sarcoma may occur more frequently than previously supposed.
Twenty bladder biopsies from patients with primary transitional cell carcinoma were inoculated into nude mice. To date, eleven of these have grown as primary implants and three serially transplantable xenograft lines (UCRU-BL-12, UCRU-BL-13, UCRU-BL-14) have been established. The histological and ultrastructural features of human transitional cell carcinoma have been maintained in each line. Despite a relatively uniform histological appearance, several indices of occult tumor heterogeneity have been revealed. Immunocytochemical staining was negative for beta-subunit human chorionic gonadotrophin but positive for carcinoembryonic antigen only in areas of squamous differentiation. All three tumors bound peanut lectin. Flow cytometric DNA analysis of UCRU-BL-13 showed multiple aneuploid peaks, separate populations being demonstrated in different xenografts of the same generation. However, the morphologies of these tumors remained identical. On initial implantation UCRU-BL-12 and UCRU-BL-14 were near diploid but aneuploid populations became apparent with increasing passage number. Each xenograft line caused cachexia in the host mice. Treatment with the cisplatin analogue, isopropyl platinum, ameliorated the cachexia displayed by mice carrying UCRU-BL-14 but did not cause tumor regression. UCRU-BL-12, when tested with cisplatin, isopropyl platinum, and carboplatin, showed equivalent growth retardation with each drug. These xenografted human bladder cancers may be useful models for the study of heterogeneity of the tumor populations in bladder cancer and for the evaluation of new approaches to treatment.
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The incidence and patterns of argyrophilia in 25 endometrial carcinomas were analysed and correlated with other pathological features. In addition, the frequency with which argyrophilia was identified within nonneoplastic endometrium and cervix from this carcinoma group was compared with that of a control group of 25 patients without malignant disease. Using the Grimelius stain, argyrophilia was observed in 68% of endometrial carcinomas, although in 28%, only rare positive cells were identified. Seven tumours (six argyrophilic carcinomas and one small-cell undifferentiated carcinoma) were examined by electron microscopy, which revealed neurosecretory granules. Argyrophilia was also found at the ultrastructural level. ACTH and calcitonin were revealed by the immunoperoxidase technique in four of the nine argyrophilic tumours examined. Argyrophilic cells in nonneoplastic endometrium were found in 10% of the carcinoma cases and 8% of the control cases; this has not been described previously. No correlation could be established between the presence or degree of argyrophilia and histological type or grade of carcinoma, extent of tumour infiltration, or argyrophilia in nonneoplastic endometrium or cervix. We conclude that argyrophilia in endometrial carcinomas has no clinicopathological significance. The histogenesis of endometrial and cervical argyrophilic cells is discussed.