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1/8. Midline malignant B-cell lymphoma with leukemic transformation.

    This article presents a case of lethal midline granuloma on the palate of a 44-year-old woman, which had been identified histologically as B-cell lymphoma with leukemic transformation in the terminal stages. At the first visit, physical and laboratory examinations showed no remarkable findings except for a necrotizing ulcer of the palate, and the biopsy specimens only showed massive inflammatory cell infiltration and necrosis of the granulation tissue. There was a short-term resolution after treatment with cyclophosphamide and prednisolone, but the disease reactivated and the necrotic ulcerative lesion progressively advanced into the nasal cavity. Specimens from the third biopsy exhibited histologic features that were consistent with malignant lymphoma of the diffuse, mixed B-cell type. Chemotherapy with the regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone was adopted but was interrupted after a short time because of bone marrow suppression. Subsequently, large numbers of enlarged abnormal lymphocytes with a few vacuoles in the cytoplasm appeared in the circulating blood, indicating leukemic transformation of the midline lymphoma. The patient died on the seventh day after the initiation of chemotherapy. In the presentation of this case, the authors mention clinically important matters regarding midline lethal lymphoma and briefly discuss the pathophysiology and pathogenesis.
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2/8. Uterine lipoma and coincidental cervical cancer: a case report.

    Pure lipoma of the uterus is a rare clinical event, and only a few cases have been reported in the literature. Clinical symptoms and physical signs are similar to those found in leiomyomas. The histogenesis of these lesions is still unclear. However, adipose metaplasia of stromal cells or smooth muscle cells of leiomyoma were accepted hypothesis that explain histogenesis of lipomas of uterus. We report the case of a 55-year-old woman with pure uterine lipoma and coincidental cancer of uterine cervix.
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3/8. Human papillomavirus type 11 DNA in squamous cell carcinomas and pre-existing multiple laryngeal papillomas.

    The case histories of 4 patients are presented, who developed an invasive squamous cell carcinoma from pre-existing multiple laryngeal papillomatosis (two juvenile-onset and two adult-onset) during a long latency period. A series of 14 routinely processed, paraffin-embedded biopsies obtained from these patients (including both benign papillomas and carcinomas) were analysed using in situ DNA-hybridization technique with 35S-labelled Human papillomavirus (HPV) dna probes of HPV types, 6, 11, 16, 18 and 30. The lesions were also assessed by indirect immunoperoxidase (IP-PAP) technique to demonstrate the expression of HPV structural proteins. On light microscopy, morphology was consistent with HPV infection in all 14 biopsies. HPV antigen expression could not be demonstrated in any of the papillomas or carcinomas, however. HPV 11 DNA was present in high copy numbers in both the benign and malignant lesions of 2 patients, both presenting with the juvenile-onset disease. The present findings provide support for the role of HPV as an etiological agent in laryngeal squamous cell carcinoma, most probably acting synergistically with chemical or physical carcinogens (one patient received irradiation and 2 others were smokers). It seems clear that an infection by the 'low risk' HPV types 6 and 11 by no means excludes the possibility of developing a laryngeal malignancy, so far ascribed to the 'high risk' type HPV 16 only.
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4/8. Acute nonlymphocytic leukemia with basophilic differentiation.

    Four cases of acute nonlymphocytic leukemia with primitive basophilic differentiation are presented. In all four cases, study revealed philadelphia chromosome negativity, and in none were there clinical findings of chronic granulocytic leukemia. In each case, the leukemic blasts contained granules that failed to stain for peroxidase content but stained positively with toluidine blue. The former result could have led to the misclassification of the cases as lymphoid leukemias. Three of the four patients had physical findings that may have been due to circulating histamine excess. The histochemical and clinical features of these cases suggest that certain examples of leukemia with basophilic differentiation represent a distinctive variant of acute nonlymphocytic leukemia.
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5/8. Squamous cell carcinoma of the ovary.

    Benign cystic teratoma is a very common ovarian lesion; and it commonly occurs during a woman's reproductive years and most often is benign. In approximately 1% to 2% of cases, however, it can undergo a malignant transformation with a very poor prognosis. This is especially the case when disseminated disease is present. Usually the associated malignancy is squamous cell carcinoma, and radical surgery is recommended. An American Samoan woman was air-evacuated to Tripler Army Medical Center for further evaluation and therapy after having undergone an exploratory laparotomy and right ovarian cystectomy. Her pathology at the time of her initial procedure revealed a mature cystic teratoma with a malignant degenerative component. Her diagnostic evaluation upon arrival was unremarkable except for her physical exam and pelvic CT. She subsequently underwent a radical surgical procedure to include a surgical staging procedure, revealing disseminated squamous cell carcinoma with FIGO stage III disease. Whereas malignant transformation of a benign cystic teratoma is a rare occurrence, a high index of suspicion should be maintained whenever a preoperative diagnosis is encountered; a radical surgical approach with en bloc resection should be employed. Adjuvant therapy with radiation or chemotherapeutic agents in general has not been shown to improve the outcome, especially in disseminated disease.
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6/8. Intraduct papillomatosis of the breast in a peripubertal male.

    A 13-year-old boy presented with right-sided gynecomastia. Histological examination of the excised specimen revealed distention of ducts by papillary configurations of proliferating epithelium. The boy had no known family history of breast disease and physical examination revealed minor dysmorphic features, but a karyotype was normal. The possible relationship of this lesion to other proliferative lesions described in the pubertal male breast is discussed.
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7/8. Solitary adenocarcinoma metastasis mimicking sarcomatous degeneration in Paget's disease.

    A rare case of mucinous adenocarcinoma presented as a solitary, metastatic deposit to a region of Paget's disease within the peripheral skeleton. Historical, physical, radiographic, and scintigraphic findings were indistinguishable from those of sarcomatous degeneration arising from pagetoid bone. This case supports the idea that when a painful, osteolytic lesion is discovered within a region of Paget's disease, bone scintigraphy has greater value of disclosing potential multifocal or multicentric disease than for providing etiologic specificity for the principal lesion.
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8/8. Malignant transformation of recurrent respiratory papillomatosis associated with integrated human papillomavirus type 11 DNA and mutation of p53.

    Recurrent respiratory papillomatosis (RRP), usually confined to the nasopharynx, trachea, and larynx, occasionally can progress to extensive bronchopulmonary disease. Most cases of bronchopulmonary and laryngeal papillomatosis are cytologically benign and do not undergo malignant transformation; however, squamous cell carcinoma (SCC) can arise in RRP in the absence of known risk factors such as radiation and smoking. In this study, the authors investigated molecular genetic alterations occurring in a case of metastasizing SCC that arose in long-standing bronchopulmonary papillomatosis. Genomic DNA from tracheal papillomata, tracheobronchial papillomata, SCC of the lung, and a lymph node metastasis was extracted. The physical state of the human papillomavirus type 11 (HPV-11) DNA was investigated by two-dimensional gel electrophoresis. Molecular genetic alterations of the host genome were studied by direct sequencing of polymerase chain reaction-amplified gene fragments and restriction fragment length polymorphism (RFLP) analysis. Episomal and integrated forms of HPV-11 sequences were detected in histologically benign tumors, but only the integrated form of the viral DNA could be found in malignant tissue samples. Molecular genetic studies revealed that an allelic loss of the interferon-beta gene (IFNbeta-1) and an endogenous type of mutation of the p53 antioncogene were found only in the malignant lesions. Mutations were not observed in the ras, neu, or multiple tumor suppressor (MTS1/p16) genes in any specimens. The authors' data indicated that the p53 genetic mutation was associated with integration of HPV-11 in histologically malignant lesions. This association may promote a progressive genetic instability that can lead to the development and clonal expansion of malignant lesions in RRP.
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