Similar outcome of elderly patients in intergroup trial 0096: Cisplatin, etoposide, and thoracic radiotherapy administered once or twice daily in limited stage small cell lung carcinoma.

BACKGROUND: Elderly patients comprise a significant portion of patients with limited stage small cell lung carcinoma. However, the prognostic importance of age has been controversial, and concern for toxicity often hinders enthusiasm for offering full dose therapy. METHODS: In this retrospective analysis of Intergroup Trial 0096, the authors compared the outcome of patients 70 years or older to those younger than 70 years. Patients received cisplatin 60 mg/m(2), Day 1 and etoposide 120 mg/m(2), Days 1-3 for 4 cycles and either once or twice daily concurrent thoracic radiotherapy to 45 grays. RESULTS: Of 381 patients, 50 (13%) were age 70 years or older. The elderly group did not differ significantly from those younger than 70 years with respect to gender distribution, performance status, or weight loss. Severe hematologic toxicity (Grade 4-5: 61% vs. 84%; P < 0.01) and fatal toxicity (1% vs. 10%; P = 0.01) occurred more often among older patients. There were no differences in the frequency of nonhematologic toxicities. Response rate (88% vs. 80%; P = 0.11), event free survival rate (5 year, 19% vs. 16%; P = 0.18), time to local failure, and duration of response did not differ between groups. Overall survival rates (5 year, 22% vs. 16%; P = 0.05) favored those younger than 70 years. Much of the difference in overall survival rates between age groups occurred within the first 6 months on study. CONCLUSIONS: Elderly patients had similar response and survival rates compared with those younger than 70 years. However, toxicity, particularly hematologic, was greater among the elderly. Selected older patients, such as those with a good performance status, should be considered for optimum treatment approaches.

Cisplatin, doxorubicin, and cyclophosphamide plus thoracic radiation therapy for limited-stage unresectable thymoma: an intergroup trial.

PURPOSE: To determine the response rate of cisplatin plus doxorubicin plus cyclophosphamide (PAC) in patients with limited-stage unresectable thymoma. In addition, this study was undertaken to determine the toxicity, progression-free survival, and overall survival of combined-modality therapy with PAC plus radiation therapy. PATIENTS AND METHODS: Patients with a histologic diagnosis of limited-stage unresectable thymoma or thymic carcinoma were eligible. Further requirements included a Karnofsky Performance Score of > 60, no prior radiation to the chest, and adequate bone marrow, hepatic, and renal function. No patient had undergone chemotherapy previously. Patients received two to four cycles (repeated every 3 weeks) of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) followed by a total dosage of 54 Gy to the primary tumor and regional lymph nodes for patients with a stable, partial, or complete response to chemotherapy. RESULTS: From November 1983 through January 1995, 26 patients were entered onto the trial. Three patients were ineligible on the basis of pathologic review (lung cancer, germ cell cancer, lymphoma). Toxicity, primarily hematologic, was mild, with only one early death due to a perforated abdominal viscus. Among the 23 assessable patients, there were five complete and 11 partial responses to chemotherapy (overall response rate, 69.6%). The median time to treatment failure was 93.2 months (range, 3 to 99.2+ months), and the median survival time was 93 months (range, 1 to 110 months). The 5-year survival rate is 52.5%. CONCLUSIONS: PAC combination chemotherapy produces response rates in the management of patients with limited thymoma. Combined-modality therapy is feasible and associated with prolonged progressive-free survival. The benefit of combined-modality therapy over radiation therapy alone is suggested for patients with unresectable thymoma.

Synovial sarcoma: frequency of nonaggressive MR characteristics.

PURPOSE: Our objective was to examine the MR characteristics of synovial sarcoma and determine the frequency of a nonaggressive imaging appearance. METHOD: Fifteen patients with histologically confirmed cases of synovial sarcoma and prior MR examinations were seen. Retrospective analysis of imaging features included assessment of size, margins, homogeneity, internal architecture, T1- and T2-weighted signal intensities, and bone invasion. RESULTS: Five of 15 patients (33%) had well circumscribed, homogeneous lesions with a mean length of 4.8 cm. The T1-weighted signal intensity was either isointense to muscle or greater in signal intensity than muscle. The T2-weighted images demonstrated signal intensity equal to or greater than fat. The remaining 10 lesions were larger (mean length of 11.3 cm) with mild to complex levels of inhomogeneity and margins that varied from well circumscribed to infiltrating. CONCLUSION: There are two sets of MR features seen with synovial sarcoma. Small lesions of -5 cm can demonstrate a nonaggressive appearance with well circumscribed margins and homogeneous signal intensity. These tumors could be confused with benign lesions, resulting in inappropriate surgical intervention like excisional biopsies through transverse incisions. This would make future surgery more difficult. Larger lesions tend to be more heterogeneous in signal intensity.

Aspiration cytology of 131I-induced thyroiditis. A case report.

BACKGROUND: Fine needle aspiration (FNA) has become an indispensable diagnostic tool for the investigation of thyroid nodules. Although 131I may induce morphologic changes similar to those associated with external radiation, a known diagnostic pitfall, the cytology literature on the subject is very sparse. This case exemplifies the thyroid cytologic changes associated with 131I exposure. CASE: A 50-year-old male with a remote history of 131I exposure had an indurated thyroid on routine physical examination. FNA was interpreted as positive for malignant cells, and subsequently a total thyroidectomy was performed. Review of the cytologic sample revealed follicular cells with focal, marked cytologic atypia, abundant colloid, stromal fragments, and lymphocytes. The thyroidectomy specimen consisted of an indurated and nodular gland showing architecture distortion by micronodule formation, lymphocytic infiltrates, interstitial fibrosis and follicular atrophy. Marked nuclear atypia was seen in the follicular cells. CONCLUSION: FNA of thyroid glands exposed to 131I may show significantly large, atypical follicular cells in addition to classical changes of nodular goiter and/or chronic lymphocytic thyroiditis. Although the clinical history and the diffuse nature of the process may favor a benign process in most cases, the presence of marked atypia could lead to a malignant diagnosis. Pathologists, therefore, should exercise extreme caution in interpreting cases with 131I exposure.

Elevated expression of retinoic acid receptor-alpha (RAR alpha) in estrogen-receptor-positive breast carcinomas as detected by immunohistochemistry.

Retinoids modulate gene activity, cell growth and differentiation by binding to a series of nuclear receptors, i.e., retinoic acid receptors (RARs) or retinoid X receptors. Retinoic acid (RA) inhibition of estrogen receptor (ER)-positive breast carcinoma seems to be mediated through RAR alpha. Estrogens upregulate RAR alpha in ER-positive breast carcinoma cell lines. In this study we examined RAR alpha expression in the ER-positive MCF7 and ER-negative MDA-MB-231 human breast carcinoma cell lines as well as in 10 ER-negative and 9 ER-positive infiltrating ductal breast carcinoma specimens using immunohistochemistry and quantitation by image cytometry. MCF7 cells expressed twofold higher levels of RAR alpha protein than MDA-MB-231 cells. RAR alpha expression, as detected by immunostaining and quantitated by image cytometry, was upregulated in these cells by estradiol. ER-positive breast carcinoma specimens also exhibited approximately two-fold higher RAR alpha levels than their ER-negative counterparts. Thus, RAR alpha expression is significantly elevated in ER-positive breast tumors as assessed by detection and quantitation using immunohistochemical staining and image cytometry, respectively. Whether the decrease in RAR alpha protein levels and loss of RA-mediated growth inhibition in ER-negative tumor plays a role in the increased metastatic potential of ER-negative tumors remains to be determined.

Endobronchial fibrous histiocytoma.

Fibrous histiocytomas are uncommon pulmonary tumors. They generally involve only the lung parenchyma. Endobronchial involvement is extremely rare. Usually, surgical resection of the mass is required for definitive diagnosis and therapy. We report a case of benign atypical fibrous histiocytoma visualized during fiberoptic bronchoscopy and review the clinical findings and pathologic features of this tumor.

TP53 and RAS mutations in metachronous tumors from patients with cancer of the upper aerodigestive tract.

Patients who initially develop an upper aerodigestive tract cancer have an increased risk of second primary cancers. We examined TP53 and RAS mutations and p53 protein in 21 tumors from 10 patients with upper aerodigestive tract cancer who developed a metachronous tumor, to assess the genetic changes that occur in multiple primary tumors from the same individual. Thirteen of 21 (62%) tumors were found to have mis-sense mutations of either TP53 or RAS. Six tumors had TP53 mutations in codons 5 to 8 and 10 tumors from 7 patients had mutations of codons 12 or 13 of K-RAS. Only one patient had concordance of a mutation in 2 tumors; this mutation occurred in K-RAS and was accompanied by discordance of TP53 mutation. Three patients had tumors discordant for both TP53 and RAS mutations. Smoking-related tumors had TP53 and RAS mutations which were transversions in 11 (9 G:C to T:A and 2 G:C to C:G) and transitions in 3 (2 G:C to A:T and 1 A:T to G:C). Tumors not associated with smoking contained only transitions (both G:C to A:T). p53 protein was detected by immunohistochemistry in 7 of 13 (54%) tumors and was concordant in the multiple tumors of 3 patients. Three of the 7 tumors staining for p53 also had TP53 mutations. Thus, genetic alterations are discordant in multiple primary cancers and the pattern of mutations is similar to that found in patients with a single primary tumor, supporting the concept that these cancers arise independently.

Primary osteosarcoma of the ribs: CT findings.

We report the CT appearance of primary osteosarcoma of the ribs in three patients. CT evaluation is important because this lesion may present a diagnostic dilemma on chest radiographs. The tumor should be suspected if CT demonstrates dense calcification within a mass that is centered in a rib.

The role of thoracoscopy in the diagnosis of interstitial lung disease.

A study was undertaken to evaluate the safety and efficacy of thoracoscopic lung biopsy for interstitial lung disease. The relation between operative findings, pathologic findings, and preoperative computed tomographic scan findings was examined. Twenty-six patients, 10 male and 16 female, underwent thoracoscopic lung resection to diagnose interstitial lung disease. Sixteen patients were outpatients for an elective procedure; 10 were inpatients including 2 who were ventilator dependent. The mean length of operation was 54 minutes and the mean length of chest tube duration, 1.3 days. There were no deaths. Staphylococcal pneumonia developed in 1 patient postoperatively. One patient with systemic pulmonary hypertension was ventilator dependent for 48 hours. A double-lumen endotracheal tube was used in all but 2 patients. Twelve-millimeter trocar ports were used to allow easy interchange of staplers and endoscopic instruments. Biopsy of at least two lobes was performed in each patient with resection of a piece of grossly abnormal lung. A single chest tube was left routinely. The pathologic diagnosis was usual interstitial pneumonitis in 7 patients. Four patients had interstitial fibrosis and 4, granulomas. Three patients had diffuse alveolar damage and 3, Wegener's granulomatosis. Two patients had bronchiolitis obliterans with organizing pneumonia. One patient each had lymphangioleiomyomatosis, eosinophilic granuloma, and cytomegalovirus. Sixteen patients underwent preoperative computed tomographic scanning. The scans were assessed by 2 radiologists who were blinded to the surgical results. Computed tomography accurately predicted the site of disease in most instances. Four patients had at least one lobe with no evidence of disease on computed tomography but with interstitial lung disease found thoracoscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of the size of the invasive component of the primary breast carcinoma to axillary lymph node metastasis.

BACKGROUND: Invasive ductal carcinomas of the breast frequently have an intraductal (in situ) component at the tumor periphery that, in some cases, is included in the measurement of the tumor and thereby increases the size of the tumor beyond that of the invasive component. METHODS: Thirty-seven ductal carcinomas containing intraductal and invasive components were analyzed. The total tumor size, the size of the invasive component, the percentage of intraductal component, and the estimated tumor volume were assessed for each tumor. RESULTS: The mean size of the invasive component was 6.5 mm in axillary lymph node negative patients and 14.3 mm in those with axillary lymph node metastasis (P = 0.0001). The mean total tumor size was 13.7 mm and 17.6 mm (P = 0.035) and the mean percent of intraductal component was 52% and 26% (P = 0.015) in patients with negative and positive axillary lymph nodes, respectively. Ninety-two and four tenths percent of the difference in mean estimated total tumor volume between patients with negative and positive axillary lymph nodes was attributable to the difference in the volume of the invasive component alone. CONCLUSIONS: In small ductal carcinomas of the breast, the size of only the invasive component, as determined by microscopic measurement, is a better predictor of axillary lymph node status than is the total tumor size. The well established prognostic value of total tumor size largely is due to its reflection of the size of the invasive component.

Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group.

PURPOSE: The purpose of this study was to evaluate the impact of cisplatin, doxorubicin, and cyclophosphamide (PAC) in patients with advanced thymoma with respect to response rate, duration of remission, and overall survival. PATIENTS AND METHODS: Assessable patients with thymoma (n = 29) or thymic carcinoma (n = 1) with metastatic or locally progressive recurrent disease following radiotherapy were treated with intravenous cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) with normal saline hydration. Courses were repeated every 3 weeks for a maximum of eight cycles of therapy. RESULTS: Toxicity, which was primarily hematologic, was mild, with only one patient developing a fever associated with neutropenia. Three complete responses (CRs) and 12 partial responses (PRs) were observed (CR+PR rate, 50%; 95% confidence interval, 31.3% to 68.7%). Ten patients had stable disease. The median duration of response was 11.8 months (range, 0.9 to 70.5+), the time to treatment failure 18.4 months (range, 0.8 to 91.9+), and median survival time 37.7 months (range, 2 to 91.9+). CONCLUSION: This trial demonstrates that objective response rates and prolonged survival can be achieved in patients with advanced thymoma.

Nodular pulmonary amyloidosis: diagnosis by fine-needle aspiration cytology and a review of the literature.

Solitary nodular pulmonary amyloid tumor is an uncommon benign lesion which is seldom diagnosed prior to surgical extirpation. We present a case of unsuspected nodular pulmonary amyloid tumor diagnosed by fine needle aspiration cytology. A 52-yr-old-black woman, presented with a 3-cm right middle lobe mass. Percutaneous fine-needle aspiration cytology (FNA) of the mass revealed waxy amorphous material that demonstrated apple green birefringence on Congo Red Stain. Thoracotomy for diagnosis may be avoided by using FNA to diagnose these unusual lesions.

Rapid growth of pseudoangiomatous hyperplasia of mammary stroma in axillary gynecomastia in an immunosuppressed patient.

Pseudoangiomatous hyperplasia of mammary stroma is a rare, benign mesenchymal proliferation that sometimes mimics angiosarcoma. To our knowledge, it has not been reported in men. We report the first case of this unusual entity in a man. This case was most unusual in that it occurred in a clinical setting of immunosuppression, in axillary gynecomastia, and was growing rapidly.

Aspiration cytology of biphasic and monophasic synovial sarcoma. A report of two cases.

Two cases of synovial sarcoma diagnosed by aspiration cytology are described. A 15-year-old, athletic female presented with a tender midthigh mass clinically thought to be a hematoma. Aspiration cytology revealed numerous clusters of spindle cells admixed with small groups of epithelial cells. Cytokeratin and vimentin stains were positive in the epithelial and spindle components, respectively. Resection of the mass revealed a biphasic synovial sarcoma. Second, a 53-year-old male presented with a recurrent soft tissue mass 10 years after synovial sarcoma of the knee had been resected. Aspiration cytology revealed neoplastic spindle cells. Cytokeratin and vimentin preparations showed focal positivity. Resection revealed a predominantly monophasic synovial sarcoma. These cases demonstrate the utility of aspiration cytology in diagnosing both unsuspected and recurrent synovial sarcoma.

Pathogenesis of pseudoxanthomatous salpingiosis.

The abnormal localized deposition of lipofuscin-laden macrophages in the lamina propria of the fallopian tube (pseudoxanthomatous salpingiosis) is reported in two women. In both cases there was evidence of longstanding endometriosis; necrotic pseudoxanthomatous nodules of the ovary were present. Histochemical and ultrastructural analysis of the pigment confirmed that it is lipofuscin (ceroid). It is proposed that pseudoxanthomatous salpingiosis develops after an episode of acute salpingitis during which actively bleeding ovarian endometriosis leaks blood into the lumen of the fallopian tube.

Case report 792. Eosinophilic granuloma of bone.

Eosinophilic granuloma is commonly thought of as a disease of children which can occur in either the axial or the appendicular skeleton. Only approximately 10% of cases occur in patients over the age of 40 years, and only approximately 12% of lesions occur in the pelvis, with no previously illustrated cases of this combination of age and location. These facts along with the nonspecific radiographic appearance made biopsy necessary for the correct diagnosis in the patient described.