Pathology and genetics of tumours of the urinary system and male genital organs

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Pathology and genetics of tumours of the lung , pleura, thymus and heart

Head and neck cancer

A review was done of 120 cases of malignant peripheral nerve sheath tumor (MPNST) seen during a 71-year period. Of the 120 patients, 52 were males and 68 were females with a mean age at diagnosis of 35.3 years; 12 patients were younger than 20 years. The series included 62 (52%) patients with neurofibromatosis, 13 (11%) with postradiation sarcomas, and 19 (16%) with metaplastic foci. The incidence of MPNST arising in neurofibromatosis was 4.6% in the current series and 0.001% in the general clinic population. Tumors greater than 5 cm and the presence of neurofibromatosis adversely affected the prognosis (P less than 0.05). When both features were present, survival was greatly decreased. Patients with tumor in the extremities did better than those with head or neck lesions. Metaplastic foci or previous radiation at the tumor site did not alter the prognosis. Each tumor was graded 1 to 4 on the basis of cellularity, pleomorphism, mitotic index, and necrosis. No significant correlation was noted between survival and either grade or mitotic rate. Survival was improved when total rather than subtotal resection was done. This was most marked in patients with a small lesion, which may reflect the difficulty in adequately excising large tumors. Adjuvant radiation or chemotherapy did not appear to affect survival. The MPNST is an aggressive uncommon neoplasm, and large tumor size, the presence of neurofibromatosis, and total resection are the most important prognostic indicators.

Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases.

In preclinical studies, a doxorubicin liposome formulation containing polyethylene-glycol (Doxil) shows a long circulation time in plasma, enhanced accumulation in murine tumors, and a superior therapeutic activity over free (unencapsulated) doxorubicin (DOX). The purpose of this study was to characterize the pharmacokinetics of Doxil in cancer patients in comparison with free DOX and examine its accumulation in malignant effusions. The pharmacokinetics of doxorubicin and/or liposome-associated doxorubicin were analyzed in seven patients after injections of equivalent doses of free DOX and Doxil and in an additional group of nine patients after injection of Doxil only. Two dose levels were examined, 25 and 50 mg/m2. When possible, drug levels were also measured in malignant effusions. The plasma elimination of Doxil followed a biexponential curve with half-lives of 2 and 45 h (median values), most of the dose being cleared from plasma under the longer half-life. Nearly 100% of the drug detected in plasma after Doxil injection was in liposome-encapsulated form. A slow plasma clearance (0.1 liter/h for Doxil versus 45 liters/h for free DOX) and a small volume of distribution (4 liters for Doxil versus 254 liters for free DOX) are characteristic of Doxil. Doxorubicin metabolites were detected in the urine of Doxil-treated patients with a pattern similar to that reported for free DOX, although the overall urinary excretion of drug and metabolites was significantly reduced. Doxil treatment resulted in a 4- to 16-fold enhancement of drug levels in malignant effusions, peaking between 3 to 7 days after injection. Stomatitis related to Doxil occurred in 5 of 15 evaluable patients and appears to be the most significant side effect in heavily pretreated patients. The results of this study are consistent with preclinical findings indicating that the pharmacokinetics of doxorubicin are drastically altered using Doxil and follow a pattern dictated by the liposome carrier. The enhanced drug accumulation in malignant effusions is apparently related to liposome longevity in circulation. Further clinical investigation is needed to establish the relevance of these findings with regard to the ability of liposomes to modify the delivery of doxorubicin to solid tumors and its pattern of antitumor activity.

https://cancerres.aacrjournals.org/content/canres/54/4/987.full.pdf

Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes.

Two hundred and seventy-four consecutive patients with measurable metastatic breast cancer, without prior exposure to cytotoxic agents were treated with tamoxifen, 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). The initial 133 patients received doxorubicin by bolus IV administration and for the next group of 141 patients doxorubicin was administered via a central venous catheter over a 48-hour (79 patients) or 96-hour (62 patients) continuous infusion schedule. Patients treated with bolus doxorubicin had this agent discontinued usually when 450 mg/m2 were reached; for patients in the infusion group treatment was continued until evidence of progressive disease or clinical or subclinical cardiac dysfunction developed. The complete remission rate was 21% the partial remission rate, 59%. There were no differences in response rate, response duration, or survival duration between groups of patients treated with doxorubicin by bolus, 48-hour or 96-hour infusion FAC. The incidence of moderate and severe nausea and vomiting was lower in the group of patients treated with infusion FAC as compared to bolus FAC (P less than 0.001); however, the incidence of mucositis was higher in the infusion group than in the bolus group (P less than 0.001). Doxorubicin administered by continuous infusion schedules was less cardiotoxic than when administered by bolus, as shown by a greater than 75% decrease in the frequency of clinical congestive heart failure at cumulative dosages greater than or equal to 450 mg/m2 (P = 0.004). Doxorubicin administered as a 48-hour or 96-hour continuous IV infusion is safer, and better tolerated than doxorubicin administered by bolus.

Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma

The histologic characteristics of 29 nasal tumors previously diagnosed as neuroblastomas, unclassified carcinomas, or unclassified malignant neoplasms were reviewed. Electron microscopy was performed in 17. Nine tumors were neuroblastomas; six of these were classical neuroblastomas while the other three exhibited olfactory differentiation in addition to the classical neuroblastoma component. Areas of ganglioneuroblastoma were found in the metastasis of one of the three olfactory neuroblastomas. Twenty tumors were classified as neuroendocrine carcinoma because all showed a neuroendocrine pattern with remarkably uniform cells growing from benign glandular epithelium; membrane bound granules were present in the cytoplasm of cells of the ten cases in this group examined by electron microscopy. The mean age of the patients with neuroblastomas was 20 years; survival in this group was 75% at five and seven years, respectively, and 67% at ten years. Recurrences, metastasis, and death occurred within 3 years of diagnosis. There was a low percentage (25%) of multiple recurrences. The metastases were located in cervical lymph nodes, brain and spine. The mean age of the patients with neuroendocrine carcinoma was 50 years. Survival was 100% at five years, 88% at seven years, and 77% at ten years. Recurrences and metastasis in 70% of the cases occurred later than the third year. Multiple recurrences were present in 54% of the cases. The metastases affected lymph nodes, brain and spine in all cases except in one in which lungs and femur were involved. In the latter case adenocarcinoma was also present in addition to the neuroendocrine carcinoma. Three patients died, all more than five years from the time of diagnosis. No correlation was found between staging and prognosis in either group, except for Stage I disease.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819821201%2950%3A11%3C2388%3A%3AAID-CNCR2820501126%3E3.0.CO%3B2-K

Neuroblastomas and neuroendocrine carcinomas of the nasal cavity: a proposed new classification.

Thirteen spindle-cell tumors of the upper respiratory tract, oral cavity, and skin of face have been studied with light and electron microscopy. Five were primary neoplasms, and 8 had recurred following radiation therapy. The primary lesions were superficially located, and, in light microscopic sections, sites of apparent continuity between tumor and overlying epithelium were observed. The electron micrographs demonstrated the presence in many tumor cells of aggregates of keratohyaline and slender bundles of tonofilaments, and occasional premelanosomes were seen. Desmosomes were present, but were few in number and poorly developed. No evidence could be found to support the concept of malignant connective tissue component. Findings justify designation of this group of tumors as spindle-cell variants of squamous carcinomas.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197012%2926%3A6%3C1311%3A%3AAID-CNCR2820260618%3E3.0.CO%3B2-C

Spindle-cell variant of squamous carcinoma. A light and electron microscopic study of 13 cases.

Covers the pathology of tumors of the lung, with emphasis on lung carcinomas. It incorporates cytologic diagnosis, histology, fine needle aspiration biopsy, electron microscopy, and immunocytochemistry to help the reader diagnose tumors early and differentiate lung tumors accurately.

Tumors of the lung

Twenty-one cases of Paget's disease have been studied using histochemical, ultrastructural, and immunohistochemical methods. Eight of the tumors involved the nipple, and 13 were extramammary (11 vulvar and two anal). The antibodies used were directed against different classes of cytokeratin proteins, epithelial membrane antigen, carcinoembryonic antigen, gross cystic disease fluid protein-15, and S-100 protein. The findings of this study provide conclusive evidence that Paget's cells, regardless of their location, are adenocarcinoma cells. Intracytoplasmic mucin is scanty in Paget's cells within the nipple, but typically plentiful in the extramammary sites where the cells are frequently signet-ring cells. The common mechanism for the evolution of Paget's disease is extension of cells from an underlying carcinoma, but the possibility that some cases, particularly in the vulva, develop from intraepithelial precursors cannot be excluded.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819870315%2959%3A6%3C1173%3A%3AAID-CNCR2820590624%3E3.0.CO%3B2-R

Bruce Mackay

Papers

Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma

Neuroblastomas and neuroendocrine carcinomas of the nasal cavity: a proposed new classification.

Spindle-cell variant of squamous carcinoma. A light and electron microscopic study of 13 cases.

Tumors of the lung

Mammary and extramammary Paget's disease. An immunocytochemical and ultrastructural study.