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Biomedical subjects

M N Koss

Publications and source records attributed to M N Koss.

At least 55 records · Page 3Linked to original sources

Pleomorphic (giant and spindle cell) carcinoma is genetically distinct from adenocarcinoma and squamous cell carcinoma by K-ras-2 and p53 analysis.

Pleomorphic carcinoma (PC) of lung is a poorly differentiated epithelial neoplasm predominantly composed of pleomorphic giant and/or spindle tumor cells. The WHO classification of lung cancer recognizes spindle cell carcinoma and giant cell carcinoma as separate neoplasms related to squamous cell carcinoma (SqC) and large cell carcinomas, respectively. Further, the presence of foci of SqC or adenocarcinoma (AdC) in, respectively, 10% and 45% of PC produces additional uncertainty as to the distinctive nature of this tumor type. In this study, the authors tested the hypothesis that PC is an entity separate from SqC or AdC by evaluating the mutational spectrum seen in these tumor types. This is performed by documenting and comparing mutation type and rate of K-ras-2 and p53 genes in PC, SqC, and AdC. Comparative DNA sequence and immunohistochemical analysis were performed on 22 PC, 42 SqC, and 97 AdC. Archival formalin-fixed, paraffin-embedded tissues formed the basis of the study. Immunohistochemical staining with p53 antibody (DO-7) revealed statistically significant differences in the intensity and frequency of staining of PC (weak, 86% of cases) versus SqC (strong, 52% of cases) and AdC (strong, 27% of cases) (P < .001). Topographic genotyping with subsequent polymerase chain reaction (PCR) and sequence analysis of K-ras-2 showed mutations in significantly fewer cases of PC (9%, 2 of 22 cases) than in AdC (36%, 35 of 97 cases) or SqC (0%, 0 of 42 cases) (P < .001). Pleomorphic carcinoma also showed significantly fewer p53 point mutations (14%, 3 of 22 cases) than did AdC (27%, 26 of 97 cases) of SqC (43%, 18 of 42 cases) (P < .01). Finally, the p53 mutations in PC were more common in exon 7, whereas those in SqC and AdC were more frequent in exon 8. These findings reveal significant differences in the pattern and frequency of genetic mutations between PC and pulmonary SqC and AdC and are in keeping with the separate histopathologic classification of these tumors.

Adenocarcinoma↗

Immunohistochemical study of metalloproteinases and their tissue inhibitors in the lungs of patients with diffuse alveolar damage and idiopathic pulmonary fibrosis.

Immunohistochemical and confocal microscopic studies of the localization of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and type IV collagen were made in lung tissues from patients with normal pulmonary histology (n = 3), diffuse alveolar damage (n = 14), and idiopathic pulmonary fibrosis (n = 12). Pretreatment with pepsin revealed otherwise undetectable MMP- and TIMP-immunoreactive sites. In normal lung, MMP-2, MMP-9, TIMP-1, and TIMP-2 were localized in ciliated cells, endothelial cells, pneumocytes, macrophages, and smooth muscle cells; fibroblasts showed a strong reaction only for MMP-2. Only TIMP-2 showed co-localization with type IV collagen. Myofibroblasts and epithelial cells expressed increased reactivity for MMPs and TIMPs in both disorders. The reactivities for MMPs and TIMPs were stronger in diffuse alveolar damage. MMP-2 showed focal co-localization in capillary endothelial and disrupted epithelial basement membranes, suggesting activation of collagenolysis. A protective effect against this lysis was suggested by the extensive co-localization of TIMP-2 with type IV collagen and fibrillar collagens. Alveolar buds showed increased reactivity for MMPs and TIMPs in their lining epithelial cells, myofibroblasts, and their basement membranes; however, their matrices were mostly unreactive. These findings emphasize the complexity of the roles of MMPs and TIMPs in collagen turnover in diffuse alvcolar damage and idiopathic pulmonary fibrosis.

Adolescent↗

Primary pulmonary sarcomas with features of monophasic synovial sarcoma: a clinicopathological, immunohistochemical, and ultrastructural study of 25 cases.

We present 25 cases of a primary pulmonary sarcoma bearing histological, immunohistochemical, and ultrastructural features indistinguishable from those of monophasic synovial sarcoma of soft tissue. The patients were 11 men and 14 women between the ages of 16 and 77 years. Clinically, the most common symptoms were chest pain, cough, shortness of breath, and hemoptysis. The lesions involved all lung segments. Grossly, they varied in size from 0.6 to 20 cm and were described as soft to rubbery tumors with areas of necrosis and hemorrhage, some with cystic changes. Two lesions involved the bronchial wall and in one case the tumor was described as encircling the bronchial tree. Histologically, all of the lesions were characterized by an atypical spindle cell proliferation with a solid growth pattern. Areas of myxoid, neural, hemangiopericytic, and epithelial-like growth pattern were observed. Mitoses, necrosis, and hemorrhage were seen in all lesions in varying proportions. Immunohistochemical studies for epithelial membrane antigen (EMA) and keratin showed strong focal positivity in 25 of 25 and 23 of 25 lesions, respectively. Immunohistochemical study for vimentin showed diffuse strong positivity in all lesions. Other immunostains, including desmin, smooth muscle actin, and S-100 protein, were negative. Electron microscopy in three cases showed spindle cells with elongated nuclei containing abundant cytoplasmic rough endoplasmic reticulum and well developed desmosome type intercellular junctions. Follow-up information ranging from 2 to 20 years was obtained in 18 patients. Six patients died of their tumors, whereas four patients died of unrelated causes without evidence of recurrence or metastases. Eight patients were alive with disease (recurrence and/or metastases) from 1 to 7 years after diagnosis. Four patients were alive and well without evidence of recurrence or metastases from 2 to 20 years (mean follow-up, 12.5 years). The present group of lesions appears to constitute a distinctive and as yet previously undescribed primary sarcoma of the lung, which probably represents the visceral counterpart of monophasic synovial sarcoma of soft tissue in a pulmonary location. Because of their distinctive biology these lesions should be distinguished from a variety of primary and metastatic malignancies of the lung.

Adolescent↗

Unique pulmonary presentation of an angiomyolipoma. Analysis of clinical, radiographic, and histopathologic features.

Extrarenal angiomyolipomas are rare lesions that have been described in the liver, hard palate, skin, uterus, vagina, penis, and spermatic cord. In this report we present the clinical, radiographic, and pathologic findings of an angiomyolipoma of the lung in a 68-year-old woman without tuberous sclerosis or lymphangioleiomyomatosis. To our knowledge, this report is the first description of pulmonary angiomyolipoma. Distinction from other benign and malignant pulmonary mesenchymal lesions depends on recognition of traditional histologic criteria. In contrast to renal angiomyolipomas, study of this case and review of prior reports reveals that extrarenal angiomyolipomas are most often well demarcated, easily resected, and not associated with tuberous sclerosis.

Aged↗

Granular cell tumors of the lung. Clinicopathologic study of 20 cases.

Granular cell tumor (GCT) of the lung is a rare neoplasm comprising 6-10% of all GCT. Since it was first described in the bronchus by Kramer in 1939, less than 80 cases have been reported. We present the clinicopathologic features of 23 GCT from 20 patients. The patients ranged in age from 20 to 57 years (median, 45 years) and included 10 males and 10 females. Of the 19 patients with available histories, nine (47%) were incidental findigns and 10 (53%) had obstructive symptoms [pneumonia, 7 (37%); atelectasis, 3 (16%)]. Three (16%) had hemoptysis, and one (5%) had weight loss. The GCT were solitary in 15 patients (75%) and multiple in five others (25%). One patient had three endobronchial lesions, and another had one endobronchial and one peripheral pulmonary lesion. Three of the patients had multiple cutaneous GCT (15%). Grossly, they were polypoid or nodular, tan-yellow, and firm. Histologically, the endobronchial GCT consisted of submucosal infiltrates of round to oval cells with abundant granular cytoplasm. The tumor often infiltrated into peribronchial tissue and in one case focally infiltrated an adjacent lymph node. Hyalinized thickening of the subepithelial basement membrane was common; the overlying epithelium often showed squamous metaplasia or ulceration. In those patients with available follow-up, the clinical behavior of lung GCT was benign. Our experience supports a conservative approach to therapy in most cases unless there has been extensive postobstructive lung injury. Potential conservative therapeutic approaches include bronchoscopic extirpation, laser therapy, or sleeve resection. The histogenesis of GCT is not known, although most studies suggest a peripheral nerve sheath origin. Our immunohistochemical results with positive staining for antibodies to S100 (4/4), NSE (3/3), vimentin (4/4), and actin (4/4, focal) are consistent with this concept.

Adult↗

Liposarcoma of the anterior mediastinum and thymus. A clinicopathologic study of 28 cases.

We studied 28 cases of anterior mediastinal liposarcoma occurring in 16 males and 12 females with a mean age of 43 years (range, 14-72). Presenting symptoms included dyspnea (four cases) and chest pain (four cases), although 11 tumors were detected incidentally by routine chest radiography. Seven cases were believed to be located within the thymus. Most (i.e., 25) of the cases were of low grade, with the well-differentiated lipoma-like or sclerosing subtypes constituting 60% and the myxoid subtype constituting 28%; the remaining 12% exhibited mixed features. Three cases were pleomorphic type. Several low-grade tumors exhibited widespread, dense aggregates of mature-appearing lymphocytes and plasma cells, which occasionally obscured the mesenchymal nature of the neoplasm, suggesting instead a lymphoid neoplasm or a reactive fibroinflammatory condition. The three high-grade tumors showed combinations of pleomorphic and round cell patterns, with focal myxoid areas. Of the cases grossly arising within the thymus, only one showed extensive thymic tissue within the lesion ("thymoliposarcoma"); six others exhibited residual thymus peripheral to the tumor. Clinical follow-up in 23 cases revealed recurrence in seven patients (31.8%), with a mean interval to recurrence of 3 years. Eight patients died (mean survival, 2.6 years), one postoperatively and three following a recurrence. Fifteen patients were alive (mean survival, 2 years), four with recurrent tumor. The myxoid tumors had a somewhat more aggressive course than the well-differentiated tumors. Metastases were not observed in any of the patients.

Adolescent↗

Smooth muscle tumours presenting as pleural neoplasms.

Five smooth muscle tumours presenting as pleural neoplasma are presented. The patients were three women and two men aged between 21 and 69 years (mean = 45 years). Clinically, one patient presented with chest pain, one with empyema and the other three were asymptomatic. Two of the tumours were located in the left side of the chest cavity and three in the right side. In four cases, the lesions presented as solitary pleural-based masses that varied in size from 10-18 cm in greatest dimension: in two of these cases, involvement of the diaphragm was present in addition to the pleural involvement. In one case, the tumour was seen to totally encase the right lung simulating the growth pattern of malignant mesothelioma. Histologically, three cases displayed an atypical spindle cell proliferation with marked cellular pleomorphism, mitoses and areas of hemorrhage and necrosis. The other two cases were characterized by a bland-appearing smooth muscle proliferation of uncertain malignant potential composed of elongated cells with a moderate amount of eosinophilic cytoplasm and cigar-shaped nuclei, lacking significant nuclear pleomorphism or mitotic activity. Immunohistochemical studies showed strong positivity for alpha-smooth muscle actin in all cases, and for desmin in four of five cases, and a focal positive reaction for keratin in one case. Ultrastructural examination in one of the high-grade tumours showed features of smooth muscle differentiation. Three of the patients were treated by complete surgical excision while, in the other two patients, the lesions were incompletely resected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Extramedullary hematopoiesis presenting as posterior mediastinal mass: a study of four cases.

We present four cases of extramedullary hematopoiesis occurring in the posterior mediastinum. The patients are two women and two men between the ages of 20 and 87 years. Two patients presented with a history of thalassemia, and one had a history of anemia of undetermined etiology. One patient was asymptomatic, and the posterior mediastinal mass was detected during a routine chest radiographs. Surgical resection of the mass was performed in one patient, whereas a biopsy was performed in the other three. Histologically, all the cases showed the typical features of extramedullary hematopoiesis, namely the presence of numerous lymphocytes admixed with megakaryocytes and red cell precursors. Follow-up information ranging from 2 mo to 3 years showed that all patients are alive and well.

Adult↗

Extramedullary plasmacytomas presenting as mediastinal masses: clinicopathologic study of two cases preceding the onset of multiple myeloma.

We present two cases of extramedullary plasmacytoma presenting as a mediastinal mass and preceding the onset of full-blown multiple myeloma. The patients are a 62-year-old woman who presented with progressive dyspnea and left-sided chest pain and a 59-year-old asymptomatic man. In both patients, radiographic studies revealed a posterior and anterior mediastinal mass, respectively. Surgical resection of the tumor was performed in the two cases. The tumors were characterized by a well-circumscribed proliferation of plasma cells surrounded by residual lymph nodal tissue. Immunohistochemical studies on paraffin sections demonstrated lambda light chain restriction. Follow-up in our patients revealed that both of them developed multiple myeloma after 6 months and 2 years, respectively. One patient received treatment with melphalan and prednisone and is currently alive and well without evidence of disease, 2 years after diagnosis. The second patient died 4 years after resection of his tumor with evidence of disease in lumbar spine, skull, and lungs. Extramedullary plasmacytoma presenting as a mediastinal mass may precede the onset of full-blown multiple myeloma; therefore, institution of early systemic therapy in these patients may be of value in preventing further progression of the disease.

Chest Pain↗

Pulmonary lymphoid disorders.

Organized lymphoid aggregates are normally found within the walls of bronchi in many species and may occur, under conditions of disease, in humans. This bronchus-associated lymphoid tissue (BALT) can be viewed as an organizing principle to explain the behavior and distribution of many pulmonary lymphoid proliferations, both hyperplastic and neoplastic. The extent of lymphoid hyperplasia can vary, from multifocal proliferations that arise in and remain in the airway walls (follicular hyperplasia of BALT) to those that form a solitary mass or nodule (nodular lymphoid hyperplasia of BALT or "pseudolymphoma") to multifocal or diffuse lymphoid hyperplasia of BALT ("lymphoid interstitial pneumonitis"). It seems likely that more than one cause accounts for these proliferations. Of interest is the hypothesis that many examples of diffuse lymphoid hyperplasia associated with the acquired immune deficiency syndrome may have a viral cause, possibly human immunodeficiency virus or, in some cases, Epstein-Barr virus (EBV). Most pulmonary lymphomas are low-grade B cell lymphomas. They exhibit histological diversity in any given case, characterized by small lymphocytes with irregular nuclei and pale cytoplasm (so-called "centrocytelike" cells), scattered immunoblasts, and lymphoplasmacytic or plasma cells. Reactive germinal centers are frequently present, and this, along with the benign clinical behavior of these tumors, may cause diagnostic confusion with reactive lesions. Both the histological appearance and the clinical behavior (in particular, the tendency to recur in extranodal sites) of these low-grade lymphomas can be explained on the basis of origin in BALT. T cell lymphoproliferative processes can occur in the lung but are rare. Lymphomatoid granulomatosis (angioimmunoproliferative lesion) is an angiocentric and necrotizing, polymorphous lymphoid lesion that presents as multiple masses in the lung, involves skin and central nervous system (among other organs), may progress to histologically overt lymphoma, and is immunophenotypically predominantly a T cell process. Microscopically, a lymphohistiocytic infiltrate, including variable numbers of atypical cells, is present. Recent in situ hybridization and immunohistochemical studies have served to show EBV localized to the large cells. In addition, these atypical cells often show B cell immunophenotypic features and are present in a background of small, reactive T cells. It is therefore possible that lymphomatoid granulomatosis is a family of T cell rich lymphoproliferations driven by EBV infection of B cells and/or T cells, analagous to the EBV-associated, posttransplantation B cell lymphoproliferative disorders.

Adult↗

Primary intrapulmonary thymoma. A clinicopathologic and immunohistochemical study of eight cases.

We describe eight cases of primary intrapulmonary thymoma occurring in seven women and one man between the ages of 25 and 77 years. Clinically, all patients had initial radiographic findings of a parenchymatous intrapulmonary mass without evidence of mediastinal involvement either radiologically or at surgery. The lesions varied from 0.5 to 10 cm in greatest diameter. Five tumors were located close to the hilum, while the other three were discovered deep within the lung and in subpleural locations. In one case, the lesion appeared to arise endobronchially and infiltrate the surrounding parenchyma. In another case, in addition to the main hilar mass, there were two smaller tumor nodules found deep within the same lung. Histologically, the lesions were characterized by the classic biphasic cellular composition of thymomas, i.e., an admixture in varying proportions of epithelial cells and lymphocytes. Four cases were characterized by sheets of lymphocytes admixed with scattered epithelial cells that were separated by fibrous bands into lobules. Three cases were composed predominantly of sheets of epithelial cells admixed with scattered small lymphocytes and containing prominent perivascular spaces. In two of these cases, focal areas of spindling of the cells were noted. One case was composed predominantly of a spindle cell proliferation with perivascular spaces and numerous small lymphocytes. Immunohistochemical stains for keratin and epithelial membrane antigen in six cases highlighted the epithelial cells scattered against the lymphoid cell background. Seven patients were treated by surgery. In one patient the tumor was deemed inoperable at the time of exploration owing to extensive pleural infiltration and was treated by postoperative radiation; the lesion recurred locally in the pleura 8 years later. Clinical follow-up in three patients after surgical incision showed them to ba alive and well without evidence of disease at 10 months, 2 years, and 8 years, respectively. Two of the patients had been followed clinically for 2 and 4 years following discovery of their lung masses on routine chest radiograph before resection of their tumors. Two patients died of unrelated conditions; in one of them, the lesions had been followed clinically for 6 years before surgery; this patient died 6 months later from coronary artery disease, without evidence of recurrence or metastasis. Our findings suggest that intrapulmonary thymomas are slow-growing tumors that may respond well to surgical resection when confined to the lung. As with their mediastinal counterparts, invasive tumors will require additional treatment for the possibility of recurrence of metastasis.

Adult↗

Primary pulmonary rhabdomyosarcomas: a clinicopathologic and immunohistochemical study of three cases.

Three cases of primary pulmonary rhabdomyosarcoma in adults are presented. The patients were all men between the ages of 57 and 78 yr (mean 67.5). All patients presented with symptoms referable to their tumors, including cough, shortness of breath, pleuritic chest pain, and weight loss. In one patient, a history of tobacco and alcohol abuse was obtained. Anatomically, two tumors were located in the left upper lobe and one in the left lower lobe. Grossly, the tumors ranged in size from 6 to 11.5 cm and were tan-gray, firm masses with areas of necrosis and hemorrhage. Histologically, the tumors were characterized by a spindle cell proliferation admixed with areas showing a pleomorphic cell population with numerous rhabdomyoblasts and areas of hemorrhage and necrosis. Immunohistochemically, all three tumors showed strong positivity with desmin and myoglobin antibodies and negative staining with antibodies against keratin, epithelial membrane antigen, and S-100 protein. All patients had a fatal outcome. Two patients died a few days after admission with respiratory distress; the third one died 2 years after diagnosis with widely metastatic disease. Autopsy findings in all cases disclosed disseminated metastases to multiple abdominal and thoracic organs. Primary pulmonary rhabdomyosarcoma should be considered in the differential diagnosis of poorly differentiated pulmonary neoplasms in adults and should be distinguished from other primary and metastatic sarcomas.

Aged↗

Pulmonary involvement in systemic lupus erythematosus.

Pulmonary disorders in systemic lupus erythematosus involve a variety of clinical presentations and pathologic patterns, which can be difficult to diagnose due to systemic dysfunction, infection, or complications of therapy. The causes of dyspnea in systemic lupus erythematosus are multifactorial, and the clinical manifestations of lung disease widely vary. Biopsy is frequently relied on to evaluate and diagnose pulmonary disease in systemic lupus erythematosus. The patient who has systemic lupus erythematosus-associated lung disease is effectively treated with various immunosuppressive drugs, in conjunction with careful evaluation of the patient's systemic involvement, drug-induced complications, and the ever-present threat of infection.

Adult↗

Malignant smooth muscle tumors presenting as mediastinal soft tissue masses. A clinicopathologic study of 10 cases.

BACKGROUND: Smooth muscle tumors presenting as mediastinal soft tissue masses are extremely rare and often are mistaken for other neoplastic conditions. METHODS: Ten cases of patients with malignant smooth muscle tumors presenting as mediastinal soft tissue masses were studied and correlated with their clinical behavior. Tissues were examined histologically and with immunohistochemical stains in all cases, and by electron microscopy in two cases. RESULTS: The patients' ages ranged from 26 to 71 years (mean, 56 years); three were women, and seven were men. Three cases were located in the anterior mediastinum and seven in the posterior mediastinum. The patients with anterosuperior mediastinal tumors all presented with signs and symptoms referable to their lesions; the patients with posterior mediastinal masses (with the exception of one) were all asymptomatic. Grossly, the lesions were well circumscribed and unencapsulated, ranging from 6 to 18 cm in greatest dimension and showed a homogeneous, rubbery cut surface with prominent cystic and myxoid areas. The tumors in all patients appeared to arise from the soft tissues within the mediastinum and were unrelated to adjacent structures. In three patients, the tumors compressed and displaced the esophagus without infiltrating its wall, and in one patient, the tumor was found in close proximity, although unattached, to a large vessel. Histologically, the lesions exhibited a spectrum of morphologic appearances that ranged from low grade leiomyosarcoma with mild-to-moderate nuclear atypia and low mitotic activity (< 3/10 high power fields [HPFs]), to high grade tumors with marked nuclear pleomorphism, extensive areas of necrosis, and high mitotic activity (> 10 mitoses/10 HPFs). One case was characterized by a striking epithelioid morphology with large, round cells arranged in small clusters; another was associated with an incidental microscopic focus of thymic seminoma in the adjacent thymus. Immunohistochemical stains in all cases showed positive labeling of the tumor cells with smooth muscle actin, desmin, and vimentin antibodies. Electron microscopy in two cases showed features of smooth muscle differentiation, i.e., spindle cells surrounded by basal lamina material, immature cell junctions, and abundant intracytoplasmic filaments with focal condensations. All patients were treated with surgical excision. On follow-up, three patients with Stage IIIb and IVa tumors died 2-7 years after surgery, and two patients with Stage Ib and IIb were alive and well 4 and 6 years after surgery, respectively. CONCLUSION: Leiomyosarcomas may arise as primary tumors originating from mediastinal soft tissues in both anterior and posterior compartments. Because of their large size and frequent areas of cystic and myxoid degeneration, they may be confused histologically with neural or other neoplasms. As with their counterparts in other soft tissue locations, histologic grade and clinical stage are the most useful parameters for assessing prognosis.

Adult↗

Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases.

BACKGROUND: The authors undertook this study to define the clinical and histologic characteristics of spindle and giant cell carcinomas of the lung and the survival and prognostic features of these tumors. METHODS: Seventy-eight cases of pleomorphic (spindle and/or giant cell) carcinoma of the lung were studied by light microscopy and immunohistochemistry to establish clinical, gross, and histologic parameters. Follow-up information was obtained from contributing physicians and analyzed by statistical means to determine prognostically significant parameters. RESULTS: The patient population consisted of 57 men and 21 women (male to female ratio, 2.7 to 1) between the ages of 35 and 83 years (mean, 62 years). Clinically, 58 patients (80%) presented with symptoms including thoracic pain, cough, and hemoptysis, whereas 14 (18%) were asymptomatic. At the time of diagnosis, 41% of the patients had clinical Stage I lesions, 6% Stage II lesions, 39% Stage III lesions, and 12% Stage IV lesions. Histologically, foci of squamous cell carcinoma were present in 8% of the tumors, large cell carcinoma in 25%, and adenocarcinoma in 45%. The remaining 22% of neoplasms were completely spindle and/or giant cell carcinomas. Spindle and giant cell carcinomas were found together in 38% of the patients. In the 69 patients for whom follow-up information was obtained, 53 (77%) died within 7 days to 6 years after diagnosis, with a 23-month mean survival (median, 10 months) (Kaplan-Meier method). There was a significant shortening of survival for patients with tumor size greater than 5 cm, clinical stage greater than 1, and lymph node involvement. The presence of nodal metastases was the most significant single prognostic factor, whereas the presence of squamous or adenocarcinomatous differentiation did not have an impact on length of survival. CONCLUSIONS: The frequency with which spindle and giant cell carcinomas are found together, their frequent association with other histologic subtypes of lung carcinoma, and the similar clinicopathologic features of these tumors suggest that they are best regarded as one type of lung cancer called pleomorphic carcinoma.

Adenocarcinoma↗

Benign and malignant salivary gland-type mixed tumors of the lung. Clinicopathologic and immunohistochemical study of eight cases.

BACKGROUND: Primary lung tumors showing features of salivary gland-type neoplasms are extremely rare. METHODS: Eight patients with primary lung neoplasms showing light microscopic and immunohistochemical features of salivary gland-type mixed tumors were studied. RESULTS: The patients were six women and two men, ages 35-69 years (mean, 52.5 years). The tumors ranged from 2 to 16 cm in greatest diameter. In two patients the lesions presented as polypoid endobronchial lesions obstructing the lumen; in another two patients the lesions were found in close proximity or in continuity with a bronchus; in three patients, the lesions presented as peripheral parenchymatous nodules unrelated to a bronchus; and in one patient, the relationship to the bronchus could not be determined. Histologically, the lesions were biphasic, showing admixtures in varying proportions of epithelial elements containing a predominant myoepithelial cell population with a stromal component containing an abundant myxoid or focally chondroid matrix. Immunohistochemical studies showed strong positivity of the cells in the epithelial component with low molecular weight keratins (CAM 5.2), and to a lesser extent with broad spectrum keratin, actin, and vimentin antibodies. The cells also showed variable reactivity in the epithelial and nonepithelial elements with S-100 protein and glial fibrillary acidic protein. Six tumors were grossly and histologically benign; in two patients, the tumors were larger, locally invasive, and showed more atypical histologic features. All patients were treated with surgical excision. On follow-up, of the six patients with histologically benign-appearing tumors, one was alive and well 6 years after surgery; another died 4 years after surgery of a second unrelated malignancy; one died during the immediate postoperative period of myocardial infarction; and three have been lost to follow-up. In the two patients with histologically atypical lesions, the tumors recurred and metastasized after 2 and 3 years, respectively, with one of them leading to death caused by widespread metastases and superior vena cava syndrome. CONCLUSIONS: Review of the literature and the findings in the current series indicate that salivary gland-type mixed tumors of the lung may present with a spectrum of histologic features and clinical behavior, ranging from benign to frankly malignant, similar to that observed for their salivary gland counterparts. Size of the lesion at the time of presentation, extent of local infiltration, and degree of mitotic activity appear to be the most reliable prognostic features of these tumors.

Actins↗

Prognostic factors in pulmonary fibrohistiocytic lesions.

BACKGROUND: The spectrum of pulmonary fibrohistiocytic lesions (PFL) ranges from benign fibrohistiocytoma or inflammatory pseudotumor, fibrohistiocytic type (IP), to fibrohistiocytic lesions of borderline malignant appearance (B), to unequivocal malignant fibrous histiocytoma (MFH). The authors reviewed a spectrum of PFL in an attempt to define their natural history and establish independent factors of prognostic significance. METHODS: Thirty-one fibrohistiocytic lesions were analyzed by multiple clinical, gross, and microscopic factors. Prognostic factors were evaluated by univariate and multivariate Cox proportional hazards models. RESULTS: After histopathologic review, the cases were classified into IP (15 cases), B (3 cases), and MFH (13 cases). IP tended to occur in younger patients (median age, 30 years; range, 11-64 years) than did MFH (median age, 54 years; range, 12-81 years) (P = 0.03). All 15 patients with IP and 3 patients with B survived. Local recurrence developed in 2 patients with IP and 6 patients with MFH. Distant metastases occurred in 7 patients with MFH. Eight of 13 patients with MFH died of disease, with a median survival time of 16 months (range, 6-36). For all pulmonary fibrohistiocytic lesions, univariate Cox regression analysis disclosed several statistically significant prognostic factors associated with mortality: metastasis (P = 0.0005), significant necrosis (P = 0.0015), local recurrence (P = 0.003), bizarre giant cells (P = 0.0282), mitoses greater than or equal to 3 per 50 high-power fields (P = 0.0286), stage at surgery (P = 0.002), high cellularity (P = 0.0267), and poor circumscription (P = 0.0294). Other parameters (age, sex, symptoms, laterality, location, atypical mitoses, nuclear pleomorphism, degree of fibrosis, and size) were not significant prognostic factors. By multivariate Cox regression analysis, metastasis was the most significant individual parameter (P = 0.002), overriding all other prognostic factors. With metastasis removed from the model, local recurrence (P = 0.0199) and necrosis (P = 0.037) were the other significant independent prognostic factors. CONCLUSIONS: Certain individual clinical, gross, and microscopic features have prognostic relevance in determining survival time in pulmonary fibrohistiocytic lesions.

Adolescent↗