Extrapulmonary Metastases Research Articles

Pulmonary Resection for Metastatic Osteosarcomas: A Retrospective Analysis of 21 Patients

The use of pulmonary resection for metastatic osteosarcoma as an interdisciplinary treatment concept is being established. The purpose of this study was to determine the clinical course, outcome and prognostic factors in a subset of patients having undergone aggressive polychemotherapy in the most recent period and metastasectomy. Between 1997 and 2001, 21 patients (8 men, 13 women) with pulmonary metastases from osteosarcoma of the limb underwent surgical resection. Exclusion of primary tumor recurrence and other extrapulmonary metastases was mandatory for inclusion in the study. Complete resection was achieved in 18 patients. The median follow-up was 60.6 months. Cumulative 5-year survival after complete resection was 34.2%. Of the prognostic factors analyzed, age, sex, repeated thoracotomy, and histologic grading did not influence survival. Complete resection was found to be a significant prognostic factor for survival following metastasectomy (p = 0.04). There was a tendency towards longer survival in patients with less than 7 pulmonary metastases compared to patients with more than 7 metastases, but the difference was not statistically significant (p = 0.07). With pulmonary metastases of osteosarcoma, every attempt should be made to completely resect all clinically detected metastases. Repeat thoracotomy in recurrent disease is compatible with long-term survival.

Prognostic Factors and Survival after Pulmonary Resection of Metastatic Renal Cell Carcinoma

Objective: Pulmonary metastasectomy as well as immunotherapy have reproducible, albeit limited efficacy in advanced renal cell carcinoma (RCC). We examined whether metastasectomy improved overall survival compared with results of immunotherapy. Methods: Between 1975 and 2003, 64 patients (41 men, 23 women) underwent pulmonary resection of metastatic RCC. Only patients who met the criteria for potentially curative operation, that means, control of primary tumor, ability to resect metastatic disease and no other extrapulmonary metastases, were included. Results: The overall 5-year survival was 33.4% (median survival: 39.2 months). A significant longer survival was observed using multivariate analysis in patients with complete pulmonary resection ( R0), with a 5-year survival of 39.9% and a median survival of 46.6 months in correlation to patients with incomplete resection (5-year survival 0%, median survival 13.3 months). In multivariate analysis patients with synchronous metastases had a significant worse prognosis in correlation to patients with metachronous metastases. The 5-year survival of curative resected patients with metachronous metastases was 43.7% versus 0% for synchronous metastases, respectively. In patients with solitary metastasis and R0 resection, we observed a 5-year survival of 49%, whereas the rate was 23% in patients with more than a single metastasis. When establishing prognostic groups as suggested by the International Registry based on the risk factors disease-free interval, number of metastasis and complete resection the group with the best prognosis showed a 5-year survival of 52% (median survival 75.2 months). Conclusion: Metastasectomy nowadays is the best treatment option in cases with technical resectable metastases with as much as possible good prognostic factors (metachronous metastases with long DFI, number up to 6 metastases).

TP53 codon 72 single nucleotide polymorphism (SNP) in gemcitabine (gem)/cisplatin (cis)-treated non-small-cell lung cancer (NSCLC) patients (p)

7161 Background: TP53 occupies a central role in mediating cellular responses to genotoxic insults through its effects on gene transcription and DNA synthesis and repair. The codon 72 SNP in exon 4, carried by 20–40% of the population, leads to an arginine to proline substitution (G-C transversion). We hypothesized that CC homozyogtes and C-carriers (heterozygotes) could have better response and survival Methods: 202 stage IV NSCLC p were included from August 2001 to July 2002. TaqMan 5' nuclease assay was used to examine TP53 72 SNP from baseline peripheral blood lymphocytes. Results:: p characteristics: median age: 61; 91% male; PS 0: 23.4%, 1: 62.7%, 2: 13.9%; adenocarcinoma: 43.1%, pleural effusion: 16%. Overall: response rate (RR) 38.6%; time to progression (TTP) 6 months (m); median survival (MS) 10.56 m. TP53 72 genotypes: GG 60.4%; GC 34.4%; CC 5.2%. By genotype: RR: GG 43%, GC: 38.5%, CC 40%; TTP: GG 6 m, GC 5.8 m, CC 8.7 m; MS: GG 9.8 m, GC 12.3 m, CC 10.5 m. For p with extrapulmonary metastases, those with PS 0 had a lower risk of progression than those with PS 1 (hazard ratio = 0.4; P=0.006); TTP 8.7 m vs 4.4 m (P=0.007). Such differences were not found for p with pulmonary metastases Conclusions: Although TP53 72 SNP was an attractive candidate marker for chemotherapy outcome, our results provide little support for this hypothesis. Intriguingly, among p with good PS, those with extrapulmonary metastases and PS 0 had significantly better outcome than those with PS 1. No significant financial relationships to disclose.

TP53 codon 72 single nucleotide polymorphism (SNP) in gemcitabine (gem)/cisplatin (cis)-treated non-small-cell lung cancer (NSCLC) patients (p)

7161 Background: TP53 occupies a central role in mediating cellular responses to genotoxic insults through its effects on gene transcription and DNA synthesis and repair. The codon 72 SNP in exon 4, carried by 20–40% of the population, leads to an arginine to proline substitution (G-C transversion). We hypothesized that CC homozyogtes and C-carriers (heterozygotes) could have better response and survival Methods: 202 stage IV NSCLC p were included from August 2001 to July 2002. TaqMan 5' nuclease assay was used to examine TP53 72 SNP from baseline peripheral blood lymphocytes. Results:: p characteristics: median age: 61; 91% male; PS 0: 23.4%, 1: 62.7%, 2: 13.9%; adenocarcinoma: 43.1%, pleural effusion: 16%. Overall: response rate (RR) 38.6%; time to progression (TTP) 6 months (m); median survival (MS) 10.56 m. TP53 72 genotypes: GG 60.4%; GC 34.4%; CC 5.2%. By genotype: RR: GG 43%, GC: 38.5%, CC 40%; TTP: GG 6 m, GC 5.8 m, CC 8.7 m; MS: GG 9.8 m, GC 12.3 m, CC 10.5 m. For p with extrapulmonary metastases, those with PS 0 had a lower risk of progression than those with PS 1 (hazard ratio = 0.4; P=0.006); TTP 8.7 m vs 4.4 m (P=0.007). Such differences were not found for p with pulmonary metastases Conclusions: Although TP53 72 SNP was an attractive candidate marker for chemotherapy outcome, our results provide little support for this hypothesis. Intriguingly, among p with good PS, those with extrapulmonary metastases and PS 0 had significantly better outcome than those with PS 1. No significant financial relationships to disclose.

Pediatric osteosarcoma pneumonectomy for pulmonary metastases: Is it justified?

8565 Background:Over the past 25 years, 95 of 210 patients (pts) under 20 years of age were subjected to surgical procedures for resection of pulmonary metastases (PM). This included completion pneumonectomy (CPN) in five pts and removal of the RML and RLL in another pt. Interval from diagnosis to detection of PM ranged from 1.5 to 2 yrs. Interval from removal of the last PM to CPN ranged from 1.7 to 3 yrs. Pts were considered candidates for CPN provided the following criteria were met: 1) Despite responses, all PM could not be eradicated with chemotherapy; 2) PM were always confined to one lung; 3) Primary tumor was extirpated; 4) No evidence of extra PM; 5) Existing PM could not be extirpated by wedge resection or lobectomy; 6) Pulmonary function would be adequate after CPN. Methods:Pulmonary function tests obtained. CPN performed. After CPN additional chemotherapy administered. Four pts were also treated with radiation therapy (45–50 Gy) to sites of suspected residual microscopic disease with methotrexate to potentiate radiotherapeutic effect. Results:No significant post operative complications. Four of six pts are alive and disease free (10.5, 4.5, 1, and 0.3 yrs) post CPN. Cause of death: One pt: inoperable left paraspinal mass with the remaining lung clear. Second pt: tumor invasion into hilar lymph nodes and pericardium. Conclusions:Long term survival following CPN appears attainable in some pts who meet the criteria described above. Important indications appear to be inability to eradicate PM by chemotherapy and inability to perform wedge resection or lobectomy. However, the long surveillance period with continual absence of disease in the contralateral lung, i.e. 3.2–5 yrs from diagnosis, was probably the major eligibility criterion. No significant financial relationships to disclose.

Imaging findings of extrapulmonary metastases of osteosarcoma

Purpose: To review imaging findings of extrapulmonary metastasis from osteosarcoma and to evaluate them for any consistent pattern and correlation between imaging findings. Materials and methods: This study was retrospectively conducted in 13 patients with extrapulmonary metastasis of pathologically confirmed osteosarcoma. We evaluated the radioisotope (RI) scans ( n=16), ultrasonography (USG) ( n=4), computed tomography (CT) scans ( n=10), MRIs ( n=6), clinical records, and pathological reports for assessment of imaging findings and correlation between radiologic findings and RI uptake of the lesions. Points evaluated were the following: uptake on RI scans, presence of mineralization on CT, and MRI, size, enhancement pattern, attenuation on CT, signal intensity (SI) on MRI, and echogenicity on USG. Results: Extrapulmonary metastatic sites were diverse, including another bone other than the primary site ( n=6), lymph node ( n=4), pleura ( n=2), liver ( n=2), pancreas ( n=1), kidney ( n=1), peritoneum ( n=1), muscle ( n=1), and subcutaneous fat layer ( n=1). One patient had tumor growth within the pulmonary artery and jejunum. Among 21 metastatic sites in 13 patients, bone scan was performed in 16 cases and RI uptake was detected in 10 lesions. Calcification was detected in eight lesions on radiologic imaging, including plain radiography, USG, CT, and MRI. Two lesions showed RI uptake without definite calcification or ossification on MRI and plain radiography, respectively. We analyzed the enhancement pattern and mass size in 18 metastatic sites and these factors had poor correlation with uptake on RI scans. Conclusion: The sites and imaging findings of extrapulmonary metastasis of osteosarcoma were variable. All the lesions with mineralization were detectable on RI scans prior to radiologic imaging. RI scan has a limited role in the evaluation of metastatic lesions without mineralization.

Pulmonary metastases from uterine malignancies: results of surgical resection in 133 patients

ObjectiveThe long-term results of the surgical treatment for patients with pulmonary metastases from uterine malignancies were clarified. MethodsA total of 133 patients who underwent pulmonary metastasectomy for uterine malignancies were enrolled in the Metastatic Lung Tumor Study Group of Japan between March 1984 and February 2002. These patients constituted the study population, and their clinical, pathologic, and prognostic data were retrospectively analyzed. ResultsThe morbidity and mortality rates related to the operation were minimal (1% and 1%, respectively). The 5- and 10-year survivals after the surgical resection in all cases were 54.6% and 44.9%, respectively. The 5-year survivals for each histologic type were estimated to be 46.8% for squamous cell carcinoma (n = 58), 40.3% for cervical adenocarcinoma (n = 13), 75.7% for endometrial adenocarcinoma (n = 23), 86.5% for choriocarcinoma (n = 16), and 37.9% for leiomyosarcoma (n = 11). In the univariate analysis, the following were shown to be associated with poor survival: primary tumor in the cervix, short disease-free interval (<12 months), large number of resected metastases (≥4), and large tumor size (≥3 cm). After mutual adjustment, short disease-free interval (<12 months) alone was related to risk of death (hazard ratio = 2.26, 95% confidence interval = 1.06-4.78) for 105 patients, excluding patients with choriocarcinoma and miscellaneous histologic types. ConclusionPulmonary metastasectomy for uterine malignancies is a safe and acceptable treatment to improve survival. Patients with a disease-free interval of 12 months or more are good candidates for this treatment if there is adequate control of the primary tumor without extrapulmonary metastasis.

Mouse Lung Neuroendocrine Carcinomas: Distinct Morphologies, Same Transcription Factors

Constitutive expression of human achaete-scute homolog-1 (hASH-1) in combination with simian virus large T antigen under the Clara cell 10-kDa secretory protein (CC10) promoter results in adenocarcinomas with focal neuroendocrine (NE) differentiation. Mice carrying conditional alleles for both Rb-1 and p53 in lung epithelial cells develop aggressive lung tumors with similarities to human small cell lung cancers, including high level expression of ASH-1, NE markers, and extrapulmonary metastases. Tumors in both models originate from bronchiolar epithelium, reveal a range of premalignant changes, express thyroid transcription factor-1 (TTF-1), a marker of peripheral airway cell lineage, and display varying degrees of bidirectional epithelial/NE differentiation.

Prognostic factors and survival after complete resection of pulmonary metastases from colorectal carcinoma: Experiences in 167 patients

ObjectiveSurgical resection is an important form of treatment for pulmonary metastases from colorectal carcinoma. We analyzed the clinical course, outcome, and prognostic factors after surgery. MethodsBetween 1985 and 2000, 167 patients (103 men, 64 women) underwent complete pulmonary resection of metastatic colorectal carcinoma. Only patients who met the criteria for potentially curative operation, in particular, control of the primary tumor, ability to resect all metastatic disease, and no other extrapulmonary metastases, were included. ResultsThe overall 5-year survival was 32.4%. A significantly longer survival was observed in multivariate analysis in patients without lymph node involvement compared with patients with pulmonary or mediastinal lymph node metastases or both. The number of pulmonary metastases significantly influenced survival. In patients with a solitary metastasis, we observed a 5-year survival of 45%, whereas the rate was 19.8% in patients with more than a single metastasis. In multivariate analysis, we also found the prethoracotomy carcinoembryonic antigen serum level to be an independent significant prognostic factor for survival. In patients with a serum carcinoembryonic antigen level exceeding 5 ng/mL and in patients with a serum carcinoembryonic antigen level in the normal range, the 5-year survivals were 22.7% and 48.3%, respectively. ConclusionsWe conclude that pulmonary resection of metastatic colorectal carcinoma is safe and results in long-term survival. Thoracic lymph node metastases, serum carcinoembryonic antigen level before metastasectomy, and the number of pulmonary metastases were identified as prognosis-related criteria for surgery.

Alu profiling of primary and metastatic nonsmall cell lung cancer

The metastatic potential of nonsmall cell carcinoma of lung (NSCLC), is currently recognized post factum, when lymph nodes or distant organs are already involved. Our ability to determine which tumors have acquired metastatic potential could help direct therapy to be more aggressive or less aggressive based upon this information. Evaluation of microsatellite instability via detection of LOH at specific loci may be useful in identifying specific markers and/or genes associated with this process. We examined Alu insertional elements as a potential marker of genetic changes associated with the metastatic potential of NSCLC. We analyzed archived, paraffin embedded tissue from 20 proven cases of NSCLC. DNA was extracted from 10 micron paraffin sections and amplified using an Alu PCR protocol. This technique does not examine specific loci but rather results in a banding profile of cellular genomic DNA. Informative allelic banding patterns, noted as differences between primary and metastatic lesions from the same patient, were observed in five of six cases (83%) with intrapulmonary metastases and in only nine of 14 (64%) cases with extrapulmonary metastases. Multiple genomic changes were detected in metastatic tumor cells as compared to normal lung tissue or primary lung tumor tissue. It appears that Alu profiling may be useful in the detection of metastatic vs primary lesions, and this technique may offer a method for identifying novel genes responsible for tumor progression and metastases.

Sarcoma sinovial pulmonar primario. Presentación y diagnóstico de dos casos

Synovial sarcoma is an extremely rare primary pulmonary tumor whose description is based on a limited number of cases. We report two cases diagnosed by thoracotomy. One patient was initially treated surgically, and a later recurrence was controlled by combined chemotherapy and a second operation after three years of monitoring. In the second case, surgery was imperative to treat massive hemoptysis and was followed by combined chemotherapy after diagnosis of lesions consistent with extrapulmonary metastasis.

Prognostic factors for survival after pulmonary resection of metastatic renal cell carcinoma

Background. Pulmonary resection in metastatic renal cell carcinoma is an accepted method of treatment. The purpose of this study was to determine the clinical course, outcome, and prognostic factors after surgery. Methods. Between 1985 and 1999, 191 patients (145 men, 46 women) with pulmonary metastases from a renal cell carcinoma underwent surgical resection. Inclusion criteria for the study were the absence of primary tumor recurrence and other extrapulmonary metastases. Complete resection (CR) was achieved in 149 patients. Results. The overall 5-year survival rate was 36.9%. The 5-year survival rate after complete metastasectomy and incomplete resection was 41.5% and 22.1%, respectively. In patients with pulmonary or mediastinal lymph node metastases, we observed after complete resection a 5-year survival rate of 24.4%, whereas the rate was 42.1% in patients without lymph node involvement. A significantly longer survival was observed for patients with fewer than seven pulmonary metastases compared with patients with more than seven metastases (46.8% vs 14.5%). For surgically rendered complete resection (CR) patients with a disease-free interval of 0 to 23 months, the 5-year survival rate was 24.7% compared with 47% for those with more than a 23-month disease-free interval. By multivariate analyses, we showed that the number of pulmonary metastases, the involvement of lymph node metastases, and the length of the disease-free interval were all predictors of survival after complete resection. Conclusions. We conclude that pulmonary resection in metastatic renal cell carcinoma is a safe and effective treatment that offers improved survival benefit. Prognosis-related criteria are identified that support patient selection for surgery.

18F-Fluorodeoxyglucose positron emission tomography in small-cell lung cancer

Positron emission tomography (PET) imaging is not used routinely in small-cell lung cancer (SCLC) but has been proven useful in non-small-cell lung cancer. The performance of (18)F-fluorodeoxyglucose (FDG)-PET in patients with SCLC was evaluated in this study. Fifteen patients with proven SCLC were evaluated (8 men and 7 women; mean age, 68 years; range, 50-81 years). Among the 15 patients with SCLC, 3 were newly diagnosed and 12 had received chemotherapy or radiation therapy before PET. Five patients underwent surgery (3 newly diagnosed and 2 after therapy) after PET scan, and 14 received chemotherapy, radiation therapy, or both. The patient who was not treated with chemotherapy or radiation therapy underwent surgery only. All patients had computed tomographic (CT) scans before PET and had clinical follow-up for at least 2 months after PET. The patients received 3.4 to 4.15 mCi of (18)F-FDG intravenously after fasting for at least 4 hours. Whole-body PET scans were acquired approximately 50 min after injection by using an ADAC Laboratories C-PET plus scanner. Among the 12 patients treated before PET, 2 were found with solitary pulmonary nodules positive on PET. Subsequent surgical resection and pathology showed 1 true positive and 1 false positive (postradiation pneumonitis). Six of these 12 patients had extrapulmonary metastases or large intense hilar or pulmonary uptake on PET, or both. Four of these 12 had no evidence of abnormal FDG uptake and were considered true negatives. The 3 patients with newly diagnosed SCLC were all true positives on PET, confirmed by surgery. One false negative on CT scan was attributed to postradiation fibrosis. These preliminary data suggest that whole-body FDG-PET can provide the basis for determining which treatment modality would be the most appropriate during the early stages of SCLC, when surgery is still an option, and it is a useful tool to assess the effect of treatment in patients with this disease. A more accurate assessment of SCLC will be possible if FDG-PET scan is combined with CT during the early evaluation of these patients.

Papillary thyroid cancer with pulmonary metastases in children: Long-term prognosis

Background. Papillary thyroid cancer (PTC) in young patients may rarely be encountered with pulmonary metastases. Previous studies have suggested that, in the pediatric population, this may not portend a lethal outcome. Our present study, children with pulmonary metastases, was designed to clarify this issue. Methods. Fourteen children and young adolescents (mean age, 13.5 years; range, 9.8-17 years) with PTC and pulmonary metastases were treated at our institution between 1937 and 1998. Surgical treatment consisted of total thyroidectomy (n = 10 patients), subtotal thyroidectomy (n = 3 patients), and a biopsy only procedure (n = 1 patient). All patients who underwent thyroidectomy also underwent a variety of cervical lymph node dissections, and all patients proved to have regional nodal disease. After the operation, 12 patients were treated with ablative doses of 131I, 1 patient was treated with external beam irradiation, and all patients were placed on suppressive thyroid hormone therapy. The mean length of follow-up was 19.3 years (range, 1-45 years). Results. Regional recurrent disease developed in 2 patients (15%). No patient experienced the development of worsening pulmonary disease or extra-pulmonary metastases. All patients with recurrent disease underwent selective nodal resections. No patient died of metastatic PTC. Seven patients (50%) remain completely free of disease and are probably cured; 7 patients (50%) are asymptomatic with residual pulmonary disease. Conclusions. A stepwise treatment approach allows long-term survival and frequent cure for young patients with PTC and concomitant pulmonary metastases. (Surgery 2000;128:881-7.)

Inhibition of experimental lung metastasis by aerosol delivery of PEI-p53 complexes.

Mutations in the p53 tumor suppressor gene and the pathways mediated by the p53 protein are common in many human cancers. Replacement of functional p53 by gene therapy is a potential way of combating these cancers and the associated drug resistance and tumor growth. Aerosol delivery of genes is a noninvasive way of targeting genes to the lung for gene therapy. Here we demonstrate, using a murine melanoma lung metastasis model, that aerosol delivery of polyethyleneimine-p53 (PEI-p53) complexes inhibits the growth of lung metastasis. A significantly reduced number of visible foci were observed in C57BL/6 mice injected with B16-F10 melanoma and treated with PEI-p53 complexes by aerosol for 3 weeks at twice a week. Fifty percent of the mice in the PEI-p53-treated group exhibited no visible tumor foci. There was a significant reduction in the lung weights of p53-treated mice (P < 0.01) compared to control groups. The tumor burden was also significantly lower (P < 0.001) in mice treated with PEI-p53 complexes. No extrapulmonary metastasis was observed in the groups treated with PEI-p53 complexes compared to 50% of the mice in control groups, which showed metastasis to lymph nodes in the neck or abdomen. Treatment with PEI-p53 aerosol also led to about a 50% increase in the mean length of survival of the mice injected with B16-F10 cells. These data suggest that delivery of the p53 gene by aerosol using PEI as the gene delivery vector can inhibit the growth of lung metastasis.

High dose inhalation interleukin-2 therapy for lung metastases in patients with malignant melanoma.

The lungs are a frequent site of metastasis in patients with melanoma, and this may cause respiratory problems in the terminal phase of the illness. Inhalation interleukin (IL)-2 therapy to the lung has been piloted and appears to be well tolerated. Twenty-seven patients were treated with single agent dacarbazine and concurrent high dose inhalation IL-2 36 million IU per day). The patients previously had progressed on chemotherapy, predominately dacarbazine-based regimens. Patients included those with American Joint Committee on Cancer Stage IV melanoma, predominately those with lung metastases, but patients with extrapulmonary metastases also were allowed on the study. Five of the 27 patients experienced a complete pulmonary remission. Eight patients achieved a partial pulmonary remission, and 5 patients experienced stabilization of their disease. Eight patients developed pulmonary metastases. One patient was not evaluable. Four of the five patients who achieved a complete response and seven of the eight patients who achieved a partial response previously were treated with dacarbazine and progressed. There were no responses in extrapulmonary metastases. Side effects of treatment were minimal. The complete responses all were durable with a follow-up of 12 months, whereas patients with partial responses and stable disease progressed when IL-2 was discontinued. Inhalation therapy with IL-2 for pulmonary metastases from melanoma appears to be safe. The current preliminary study suggests efficacy although concurrent chemotherapy was given, thus confounding results to some extent. Therefore, these results need to be reproduced without concomitant chemotherapy. In addition, a strategy comprised of therapy with IL-2 inhalation until disease progression may prolong responses.

Pulmonary Cysts as the Sole Metastatic Manifestation of Soft Tissue Sarcoma: Case Report and Consideration of the Pathogenesis

A 29-year-old woman with an unusual form of pulmonary metastasis from epithelioid sarcoma of the right forearm is presented. Since she manifested left pneumothorax due to metastatic pulmonary cyst 7 years ago, the only metastatic manifestation has been the presence of bilateral multiple thin-walled pulmonary cysts; no other types of pulmonary lesions, such as nodules, cavitary lesions with thick or irregular walls, or extrapulmonary metastases, have been found. Pathologic studies revealed metastatic proliferation of sarcoma cells in the wall of the pulmonary cysts and infiltration of malignant cells inside the microscopic cavitary metastases surrounded by normal lung parenchyma.

UNUSUAL LATE EXTRAPULMONARY METASTASIS IN OSTEOSARCOMA

The major site of metastasis from osteosarcoma is the lung, and over 90% of fatalities in patients with this disease die from pulmonary metastases. Extrapulmonary disease is developing in an increasing proportion of patients, usually after pulmonary metastasis. This study reports three cases of patients with osteosarcoma that metastasized to the brain, mediastinum, intramuscular site, and pelvic cavity. The physician must be aware that extrapulmonary metastases may be present at the time a pulmonary metastasis becomes evident.

Immunohistochemical, ultrastructural and molecular study of well differentiated adenocarcinomas of the lung predominantly composed of goblet cells

In order to clarify the morphological and biological characteristics of well differentiated adenocarcinoma of the lung predominantly composed of goblet cells (WDAG), histopathological examinations, including some molecular biological procedures, were carried out using 42 surgical specimens of primary lung carcinoma which were predominantly (>50% of the total cell population) or totally composed of goblet cells. The subjects included 19 men and 21 women, ranging in age from 41 to 81 (mean 60 years old) with predominantly nodular, peripherally located lesions. Ultrastructural examination revealed characteristic apical microvillous filamentous core rootless (AFCR) in some, but not all, cases. Histologically, these AFCR corresponded well with structures stained by phosphotungstic acid hematoxylin (PTAH). The goblet cells of WDAG were divided into PTAH-positive (26 cases) and -negative (16 cases) groups. The PTAH-positive group had larger tumor size, greater number of intrapulmonary and extrapulmonary metastases and shorter disease-free interval. The immunoexpression of p53 protein (60%) and rate of K-ras point mutation (84%) were also higher in the PTAH-positive group. Therefore the goblet cell population of WDAG, though it may appear morphologically homogeneous under light microscopy, is actually composed of heterogeneous groups of cells with different histopathological characteristics and biological behavior.

Primary mediastinal nonseminomatous germ cell tumors: results of modern therapy including cisplatin-based chemotherapy.

Primary mediastinal nonseminomatous germ cell tumors (NSGCT) are uncommon neoplasms and clinically and biologically distinct from other germ cell tumors (GCT). We describe the clinical and biologic features of these patients and evaluate the results of treatment during the cisplatin era. Between 1976 and 1993, 38 patients with mediastinal NSGCT received cisplatin-based chemotherapy as part of their primary treatment. Twenty-nine of them were initially treated at the Institut Gustave-Roussy (IGR), VillejuiF, France, and nine were referred for salvage treatment. Of the 29 patients initially treated at IGR, 11 (39%) had metastasis. A complete response (CR) to therapy was obtained in 19 of 29 patients (66%) after chemotherapy and surgery. Ten patients (34.5%) have remained free of disease with a median follow-up of 89 months. All patients who did not achieve a CR died of disease. The 2-year overall survival rate for the IGR patients is 45% and the 2-year disease-free survival is 37%. Only the presence of extrapulmonary metastasis was of prognostic significance in the univariate analysis (P = .0095). None of the 20 patients who required salvage therapy is currently disease-free. Five patients developed and subsequently died of a hematologic malignancy at an interval range of 1 to 47 months from treatment of mediastinal NSGCT. Cytogenetic analysis of leukemic cells found an isochromosome of the short arm of chromosome 12 (12p) in two cases. The incidence of leukemia was 21% in patients who attained a CR. Primary mediastinal NSGCT is a clinical and biologic entity that should be distinguished from other GCT. About 40% of these patients can envisage long-term survival with modern therapy that includes cisplatin-based chemotherapy followed by surgical resection of residual masses. New strategies are required for patients who do not attain a CR. Predictive factors and improvement in therapy are required for mediastinal NSGCT-associated leukemia.