Foxp3 staining in BK virus allograft nephropathy and comparison with acute cellular rejection.

BACKGROUND: Foxp3(+)CD4(+)CD25(+) regulatory T cells are involved in maintaining immunologic self-tolerance. These cells have been investigated in acute cellular rejection (ACR) of renal allografts. In this retrospective pathological study, we evaluated Foxp3(+) immunostaining in BK virus nephropathy (BKVN). In some circumstances, BKVN may be difficult to distinguish histologically from ACR. METHODS: Sequential sections were made of 30 allograft core biopsies and stained for hematorylin and eosin (H&E), C4d, cytomegalovirus (all negative), SV40, CD3, CD20, and Foxp3. Twelve biopsies were from diagnosed BKVN cases, 12 were from diagnosed ACR cases, and six showed neither BKVN nor ACR (controls). The 100x field of maximum cellular inflammation was located and marked on the H&E stain. The same area on the CD3, CD20, and Foxp3 slides was marked. Staining lymphocytes were counted under 400x magnification. Degree of BKVN was assessed according to the Drachenberg scale; degree of ACR was assessed by the Banff criteria. RESULTS: The range of Foxp3(+) staining (cells/mm(2)) was much larger in BKVN (0-270) compared to ACR (0-35). The mean difference did not reach statistical significance owing to a large degree of overlap between the two groups. In BKVN, the Foxp3(+) infiltrate correlated with the degree of CD3(+) infiltrate (P = .012), and median Foxp3(+) infiltrate increased with Drachenberg grade of BKVN. CD3(+) cell levels were not significantly different in BKVN versus ACR. CONCLUSIONS: BKVN cases with high levels of Foxp3(+) graft infiltrates may be manifesting an immune response different from that of ACR. Positive Foxp3 correlation with Drachenberg grade suggests a down-regulatory response.

Microscopic pulmonary embolisation of an indwelling central venous catheter with granulomatous inflammatory response.

Indwelling catheters can disintegrate into tiny fragments and embolise. Once the fragments are detected radiographically, they can be removed using vascular intervention techniques. Rarely, indwelling catheters dwindle into inextricable pieces that embolise into minute pulmonary vessels and lymphatics, causing granulomatous changes microscopically. The present study reports a 54-yr-old female who had received several indwelling central lines during several abdominal surgeries over a 5-yr period. The patient developed a noncaseating granulomatous skin lesion followed by exertional dyspnoea a few months later. Chest radiographs and computed tomography showed diffuse interstitial infiltrates. Open lung biopsy showed two types of granulomas: 1) peri-lymphangitic and peri-bronchiolar non-necrotising granulomas consistent with sarcoidosis; and 2) distinct foreign body granulomas. In some of the foreign body granulomas, confocal Raman spectroscopy identified the presence of bisphenol-A-polycarbonate, a polymer commonly used in biomedical devices. The patient improved following treatment with prednisone followed by methotrexate. The present case illustrates an interesting combination of two causes of granulomatous disease, the importance of examining all biopsy specimens from sarcoidosis patients for foreign particles and the rare occurrence of microscopic embolisation of catheter fragments to the lung with foreign-body giant cell reaction to them.

Morphometry confirms the presence of considerable nuclear size overlap between "small cells" and "large cells" in high-grade pulmonary neuroendocrine neoplasms.

We morphometrically evaluated 5-micron H&E-stained sections from 28 surgically resected high-grade pulmonary neuroendocrine neoplasms, including 16 small cell lung carcinomas (SCLCs) and 12 large cell neuroendocrine carcinomas (LCNECs). For each case, 200 tumor nuclei and 20 to 100 normal lymphocytes were measured. The frequency distributions of tumor cell/lymphocyte (TC/L) size ratios were plotted in bins ranging from 1 to 6, classified into 6 histogram types with TC/L size ratio peaks ranging from 2 to 6 (A-E) and a histogram with a wide distribution (F). SCLCs fit histograms A through E; LCNECs, A through F. Morphometry demonstrated considerable nuclear size overlap in high-grade neoplasms. Approximately one third of SCLCs exhibited considerable numbers of neoplastic cells that were larger than 3 normal lymphocytes, while 4 of 12 LCNECs had a predominant number of small cells. Ten tumors exhibited a B histogram with a "borderline" peak TC/L of 3. The rule that a TC/L size ratio larger than 3 helps distinguish "large" from "small" neoplastic cells was confirmed in only 9 of 28 cases. The use of more generic terminology such as "high-grade neuroendocrine carcinoma" or "grade III neuroendocrine carcinoma" for SCLC and LCNEC is discussed.

Pleomorphic (giant and/or spindle cell) carcinoma of lung shows a high percentage of variant CYP1A12.

BACKGROUND: Pleomorphic carcinoma (PC) of the lung is an aggressive epithelial neoplasm composed of giant and/or spindle tumor cells and associated with short survival. Most patients are cigarette smokers. The tumor susceptibility gene P-450 1A1 (CYP1A1) is involved in the activation of polycyclic aromatic hydrocarbons, including benzo[a]pyrene, producing DNA-damaging epoxides that lead to G:C-->T:A point mutations. Isoleucine (Ile)-valine (Val) and Val-Val genotypes of the CYP1A1 exon 7 polymorphism are associated with an increased risk for lung cancer in certain populations. METHODS AND RESULTS: We sought to determine whether 25 archival, formalin-fixed, paraffin-embedded PC samples had a modified CYP1A1 gene profile at exon 7 using allele-specific PCR amplification. KRAS mutation status was available for all samples. Previous investigations have shown 0.88 Ile-Ile, 0.12 Ile-Val, and rarely, Val-Val as normal baseline population frequencies. Conversely, the markedly different PC CYP1A1 population frequencies were more likely to have the heterozygote variant alleles: 0.24 (six cases, Ile-Ile) and 0.76 (19 cases, Ile-Val; P <.001). CYP1A1 genotypes were found to be similar in both tumor and nontumor samples in a given case. All KRAS-mutated cases were Ile-Val heterozygotes. CONCLUSION: The increased propensity for the variant CYP1A1 allele may be the contributing factor to PC pathogenesis and may also result from KRAS mutations in these tumors.

Pulmonary atypical carcinoid: predictors of survival in 106 cases.

Pulmonary neuroendocrine tumors (NE) include a spectrum of tumors from typical carcinoid (TC) to atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCLC). Little is known about prognostic predictors for AC because of its rarity. Survival analysis was performed on 106 ACs with clinical follow-up from the AFIP and the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). The tumors fulfilled the 1999 WHO/IASLC criteria for AC of a NE tumor with a mitotic rate of 2 to 10 per 2 mm(2) of viable tumor or coagulative necrosis. Multiple clinical and histologic features were analyzed by Kaplan-Meier and Cox regression analysis. Of the clinical features, higher stage (P = .003) and a tumor size of 3.5 cm or greater (P = .003) were associated with a worse prognosis. Features that were histologically unfavorable by univariate analysis were mitotic rate (P =.002), pleomorphism (P = .018), and aerogenous spread (P =.007). Histologically favorable features by univariate analysis were the presence of palisading (P = .008), papillary (P = .039), pseudoglandular (P =.026), and rosette (P = .022) patterns. Female gender showed a trend toward a poorer prognosis (P =.085) and was included in the multivariate model. Multivariate analysis stratified for stage showed mitoses (P<.001), a tumor size of 3.5 cm or greater (P =.017), and female gender (P =.012) to be the only negative independent predictors of prognosis and the presence of rosettes (P = .016) to be the only independent positive predictor. We further divided the AC into subgroups of low (2 to 5 mitoses/2 mm(2)) and high (6 to 10 mitoses/2 mm(2)) mitotic rate and compared the survival with TC and with LCNEC. Within the category of AC, the patients with a higher mitotic rate had a significantly worse survival than those with a lower mitotic rate (P<.001) stratified for stage. Five- and 10-year survival rates for AC (61% and 35%, respectively) stratified for stage were significantly worse than for TC and better than that for LCNEC and SCLC. Chemotherapy or radiation therapy was given in 12 of 52 and 14 of 52 cases, respectively, but the data were insufficient to evaluate tumor response. We conclude that AC is an aggressive neuroendocrine neoplasm with survival intermediate between TC and LCNEC and SCLC. Higher mitotic rate, tumor size of 3.5 cm or greater, female gender, and presence of rosettes are the only independent predictors of survival. Surgical resection remains the treatment of choice, and the role of chemotherapy and radiation therapy remains to be proven.

Thymohemangiolipoma, a rare histologic variant of thymolipoma: a case report and review of the literature.

We report a case of a thymic neoplasm in an 18-year-old woman who presented with chest discomfort and an anterior mediastinal mass. The surgically resected tumor showed abundant adipose tissue admixed with thymic tissue and numerous medium-caliber blood vessels. We consider this tumor a rare variant of thymolipoma and designate it as thymohemangiolipoma. Because of its benign nature, it should be distinguished from other mediastinal lesions.

Pulmonary capillaritis.

Vasculitis, inflammation, and necrosis of blood vessels can involve any size or type of vessel in the pulmonary vasculature, including the capillaries, so-called capillaritis. Although pulmonary capillaritis is a histopathologic diagnosis that is not pathognomonic of a specific disorder, it usually signals the presence of an underlying systemic vasculitis or collagen vascular disease. Patients with pulmonary capillaritis usually present with bilateral infiltrates on chest radiographs and can be acutely ill with diffuse alveolar hemorrhage that may be life threatening. Therapy depends on diagnosis of the underlying disease that gave rise to the capillaritis. Since many of the disorders leading to capillaritis are treated by immunosuppression with corticosteroids and cyclophosphamide or azathioprine, infection must be excluded early in the course of therapy.

A clinicopathologic study of 100 cases of pulmonary sclerosing hemangioma with immunohistochemical studies: TTF-1 is expressed in both round and surface cells, suggesting an origin from primitive respiratory epithelium.

Pulmonary sclerosing hemangioma (SH) is a lung neoplasm of uncertain histogenesis that is composed of two major cell types: surface and round cells. The authors studied 100 cases of pulmonary SH that presented as a peripheral (95%), solitary (96%) mass of less than 3 cm in diameter (74%) in asymptomatic patients who were mostly women (83%) with a mean age of 46.2 years. Immunohistochemistry of multiple epithelial, mesothelial, pneumocyte, neuroendocrine, and mesenchymal markers was performed on 47 cases to investigate the histogenesis of this neoplasm. Both surface and round cells stained with epithelial membrane antigen (EMA) and thyroid transcription factor-1 (TTF-1) in more than 90% of cases; however, the round cells were uniformly negative for pancytokeratin and positive for cytokeratin-7 and CAM 5.2 in only 31% and 17% of cases, respectively. Surfactant proteins A and B as well as Clara cell antigen were positive in varying numbers of surface cells but they were negative in the round cells. Neuroendocrine cells either as isolated scattered cells or as a tumorlet within the center of SH were detected (chromogranin, Leu-7, synaptophysin positive) in three cases. The expression of TTF-1 in the absence of surfactant proteins A and B and Clara cell antigens in the round cells of SH suggests that they are derived from primitive respiratory epithelium. The alveolar pneumocytes and neuroendocrine cells may either represent phenotypic differentiation of a primitive respiratory epithelial component or they may correspond to non-neoplastic entrapped or hyperplastic elements. The concomitant positivity of both cell types in SH for TTF-1 and EMA, and the negativity of round cells for pancytokeratin and neuroendocrine markers, provide useful clues not only for histogenesis but also for the diagnosis of this lung neoplasm.

Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases.

Nodular lymphoid hyperplasia is a controversial entity in which its existence in the lung has been doubted. The current opinion is that most, if not all, such cases represent extranodal marginal zone B-cell lymphomas masquerading as reactive lesions. We found 14 cases of nodular lymphoid hyperplasia in the files of the Pulmonary Department at the Armed Forces Institute of Pathology from 1974 through 1998. All had clinical histories and hematoxylin-eosin slides. In 12 of 14 with paraffin blocks, we applied immunohistochemical antibodies for CD20, CD3, CD43, CD5, bcl-2, bcl-1, CD45RA, and kappa and lambda immunoglobulin light chains. Molecular genetic analysis was performed on paraffin sections in 10 of 14 by the polymerase chain reaction for rearrangements of the immunoglobulin heavy chain gene and the minor and major break-point regions of the chromosomal translocation t (14;18). There were eight women and six men ranging in age from 19 to 80 years (median, 65 yrs). Most lesions (71%) were incidental findings on routine chest x-rays. Most patients (64%) had a single lesion by chest x-ray whereas the remainder had two to three lesions, except for one patient who had "multiple" lesions. There was associated regional lymphadenopathy in five of 14 cases (36%) which, on biopsy, proved to be reactive follicular hyperplasia. The only treatment was surgical excision. Of the seven patients with follow-up information from 8 months to 6 years (mean, 30 mos), none had clinical recurrence and no patient died of disease. The histology and immunophenotype of the lesions were strikingly similar, including abundant reactive germinal centers, intense interfollicular polyclonal plasmacytosis, and a variable degree of interfollicular fibrosis. No case showed a molecular rearrangement of the immunoglobulin heavy chain gene or the minor or major break-point region of the t (14;18). We conclude that nodular lymphoid hyperplasia of the lung, although rare, does exist and deserves its place in the spectrum of reactive pulmonary lesions that ranges from follicular hyperplasia to diffuse hyperplasia of the bronchus-associated lymphoid tissue (lymphoid interstitial pneumonitis).

Primary anaplastic large cell lymphoma of the lung: a clinicopathologic study of five patients.

Primary anaplastic large-cell lymphoma is a rare malignancy in the lung. Anaplastic large-cell lymphoma characteristically involves the lymph nodes or skin, with few reports from other sites. We studied the clinical and pathologic features of five cases of anaplastic large-cell lymphoma limited to the lungs. The patients were three women and two men aged 27 to 66 years (mean, 44.6 y) The tumors ranged in size from 1.1 to 5 cm. All patients were CD 30 (Ki-1) positive and CD 15 (LeuM-1) negative. Epithelial membrane antigen immunoreactivity was seen in two patients. Epstein-Barr virus was not detected by immunohistochemistry (four patients tested) or by polymerase chain reaction studies (three patients tested). The immunophenotypes were T cell (n = 3) and null (n = 2). Gene rearrangement studies supported the immunophenotypic findings. One patient who had underlying HIV infection died of infectious complications. One patient died at 6 months. Two patients developed recurrent disease and are alive after 42 and 51 months of follow-up. The remaining patient is alive at 8 years of follow-up without evidence of disease. ALCL can mimic metastatic or primary carcinoma and should be considered in the differential diagnosis of large cell neoplasms of the lung.

Carcinosarcomas of the lung: a clinicopathologic study of 66 patients.

Carcinosarcoma is a malignant tumor having a mixture of carcinoma and sarcoma containing differentiated mesenchymal elements, such as malignant cartilage, bone, and skeletal muscle. These tumors have been linked histogenetically to pleomorphic carcinomas; it is unclear whether their clinical behavior is significantly different. To investigate this issue, we studied 66 cases of carcinosarcomas of the lung and compared them with cases from a previously published series of pleomorphic carcinomas. Carcinosarcomas show a male-to-female ratio of 7.25:1, with a mean and median age of 65 years. They most often present as solitary masses in the upper lobes and average 7 cm in diameter. Most (62%) were endobronchial or central tumors, whereas 38% were described as peripheral. The most frequent epithelial component was squamous cell carcinoma (46%), followed by adenocarcinoma (31%) and adenosquamous carcinoma (19%), whereas sarcomatous elements most frequently included rhabdomyosarcoma, chondrosarcoma, osteosarcoma, or combinations of these elements. Survival of patients with carcinosarcomas of lung was poor, with a 5-year survival rate of 21.3%. Of several clinical and pathologic parameters, only increased tumor size (with 6 cm as the optimal cutoff point) appeared to be related to reduced survival (p = 0.0195). In comparison with patients with pleomorphic carcinoma, patients with carcinosarcomas had no significant difference in the size of their tumors (p = 1.0), stage at presentation (p = 0.883), location in the lung (p = 0.073), or their overall survival (21.3% vs 15.0%) (p = 0.1038). A significantly greater proportion of patients with carcinosarcoma had squamous cell (p = 0.004) or adenosquamous (p = 0.016) carcinoma, whereas patients who had pleomorphic carcinoma showed a significantly greater frequency of adenocarcinoma (p = 0.029) and large cell carcinoma. The histologic differences between these two types of tumor suggest that they may be different entities with similar behavior, but additional studies are warranted to investigate this hypothesis.

Pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension that mainly affects children and young adults. Its cause is unknown, although viral infections and drugs have been implicated. Patients with PVOD present with symptoms of right-sided heart failure. Radiologic examination shows prominent pulmonary arteries with Kerley B lines, pleural effusion, and mediastinal adenopathy. The definite diagnosis is made by histologic examination. Eccentric intimal fibrosis and recanalized thrombi in pulmonary veins and venules, arterialized veins, alveolar edema, and medial hypertrophy of arteries are seen on lung biopsy. No effective treatment is available; lung transplantation has been tried. The prognosis associated with PVOD is poor.

Alveolar adenoma: a histochemical, immunohistochemical, and ultrastructural analysis of 17 cases.

Alveolar adenoma of lung is a rare benign neoplasm of uncertain histogenesis. Its rarity hampers characterization of its epithelial and mesenchymal elements. Clinical and histopathologic features of 17 alveolar adenomas were reviewed. Histochemistry was performed on 10 cases, ultrastructural analysis on two, and immunohistochemistry on six cases for pneumocyte markers, thyroid transcription factor (TTF-1), surfactant protein markers pro-SP-B and pro-SP-C, and the Clara cell marker, CC10. Immunohistochemistry was performed in nine cases for desmin, smooth muscle actin, muscle-specific actin, cytokeratin, proliferating cell nuclear antigen (PCNA), factor VIII, and carcinoembryonic antigen. The mean age was 53 years. Seven cases occurred in men, and nine occurred in women. The age and sex were not known for one patient. The tumors were coin lesions on chest radiographs in asymptomatic patients except for one (cough). The mean size was 2.2 cm. The tumors were well demarcated with multiple cystic spaces containing granular material. Mostly type 2 pneumocytes lined the cystic spaces with fewer type 1 cells and no Clara cells. This was confirmed by staining for TTF-1, pro-SP-B, and pro-SP-C and by ultrastructure. CC10 was negative in all cases. The stroma varied from prominent spindle cells with a myxoid matrix to thin alveolar septa. The interstitial spindle cells resembled fibroblasts by immunohistochemistry and ultrastructure. Follow-up data available in five cases showed no recurrence at 2, 2, 5, 8, and 13 years. In summary, alveolar adenoma is a benign neoplasm consisting of an intimate admixture of alveolar epithelial and septal mesenchymal tissue. Most of the epithelial cells are type 2 pneumocytes, and the interstitial stromal cells are fibroblasts or fibroblast-like cells. Recognition of its characteristic morphological appearance allows for its distinction from other benign lesions of the lung.

Pulmonary plasmacytomas: a clinicopathologic and immunohistochemical study of five cases.

Five cases of primary plasmacytoma of the lung are presented. The patients were four men and one woman between the ages of 50 and 79 years (mean age, 57 years; median age, 54 years). Two patients presented with symptoms related to their tumor; these included cough, dyspnea, and hemoptysis. In two patients, the tumor presented as a hilar mass, whereas in the remaining three patients, the tumor was located intraparenchymally. Clinically, only one patient had a reported monoclonal gammopathy (IgG, kappa). Because of the proximal location of these tumors, three patients underwent pneumonectomy; one other underwent a lobectomy, and one had a segmental resection. Grossly, the tumors ranged from 2.5 to 8 cm in maximum diameter (mean, 4.4 cm); they were either peribronchial or involved a major bronchus. Histologically, they were characterized by sheets of plasma cells that were well differentiated in two cases and moderately differentiated in three. Amyloid was present in two cases. In four tumors, there was a monoclonal population of lambda light chain-bearing plasma cells, whereas in one, the plasma cells expressed a monoclonal kappa light chain. The tumor cells predominantly expressed IgG heavy chains in two cases. Peribronchial and mediastinal lymph nodes were involved in three cases. Follow-up information ranged from 4 days to 262 months (average, 115 months; median, 36 months). Two patients survived more than 20 years before dying of non-tumor-related causes. Two patients died 28 months and 4 days after surgery with concurrent tumor in liver and mediastinal and para-aortic lymph nodes. Comparing the present cases and those reported in the literature, we noted that the patients herein presented are, on average, older than those published previously. Combining our cases with 14 other verifiable, previously published cases, the overall 2- and 5-year survivals of pulmonary plasmacytomas are 66% and 40%, respectively. Patients with pulmonary plasmacytomas can have a long-term survival, as evidenced by two of our patients who survived 20 or more years.

Adenocarcinoma simulating mesothelioma: a clinicopathologic and immunohistochemical study of 29 cases.

We report 29 cases of adenocarcinomas whose clinical, gross, and microscopic appearance resembled diffuse malignant pleural mesothelioma. Initial criteria for inclusion in the study included availability of an open pleural biopsy or decortication specimen and microscopic evidence of neutral (periodic acid-Schiff positive) mucin in the tumor. The median age of the patients was 63 years (range, 31 to 78 years), with a peak age in the seventh decade. There were 24 men and five women. Thirteen of them had a history of smoking; six (21%) had possible or definite occupational exposure to asbestos. Three (21%) of 14 lung specimens showed ferruginous bodies and two (14%) showed microscopic evidence of asbestosis. At least 25 patients had pleural effusion, most typically unilateral. Needle biopsy of pleura showed malignancy in 10 (77%) of 13 cases. Most (20 of 29) patients underwent pleural stripping. Radiotherapy and chemotherapy was each given to three patients without effect. Median survival by Kaplan-Meier estimate was 8 months, with an 18-month survival of 13%. Histologically, glands (23 cases), nests (13 cases), tubulopapillary arrays (12 cases), or sheets (eight cases) of tumor cells were found. Spindling of neoplastic cells was seen in 10% of cases. Three (21%) of 14 lung specimens showed a subpleural adenocarcinoma. Antibodies to polyclonal CEA, Ber-EP4, Leu-M1, and B72.3 were positive in 94%, 56%, 50%, and 44% of cases, respectively. All but one of the cases stained with two or more of the antibodies CEA, Ber-EP4, Leu-M1, or B72.3. This study indicates that adenocarcinomas simulating mesothelioma are aggressive variants of peripheral adenocarcinomas with a poor prognosis, that they can show pathological evidence of asbestos exposure in a subset of cases, and that immunohistochemical and histochemical stains are useful in their differential diagnosis with diffuse malignant mesotheliomas.

Primary pulmonary ganglioneuroblastoma: a clinicopathologic and immunohistochemical study of two cases.

We present two patients with primary ganglioneuroblastoma involving the bronchial wall. The first, a 38-year-old woman, presented with signs and symptoms suggestive of multiple endocrine neoplasia, including gastric ulceration and hypercalcemia. Chest radiographic studies revealed a 3-cm nodule in the hilus of the right lung and two less-pronounced lesions in the periphery of the right lung. The second, a 20-year-old asymptomatic woman, was evaluated for a solitary mass in the upper lobe of the left lung that was peribronchial and that impinged on the lumen of a bronchus. Grossly, both neoplasms extended from bronchi, were well-circumscribed, firm, tan or white, and homogeneous, and measured 5 x 5 cm and 3 x 3 cm, respectively. Histologically, both tumors were characterized by neuroblastoma with areas of neuropil and multifocal areas of ganglion cells. Immunohistochemical studies performed in one case showed focal staining for neurofilament protein and S-100 protein and diffuse staining for neuron-specific enolase. Follow-up information showed that one patient died a few days after admission to the hospital; the second patient has remained well and without evidence of recurrence or metastases 1 year after initial diagnosis. These two cases confirm that ganglioneuroblastoma can occur as a primary pulmonary tumor in adults, presumably arising from sympathetic ganglia of the bronchus.

Constrictive (obliterative) bronchiolitis: diagnosis, etiology, and a critical review of the literature.

Constrictive bronchiolitis (CB) (or obliterative bronchiolitis) designates inflammation and fibrosis occurring predominantly in the walls and contiguous tissues of membranous and respiratory bronchioles, with resultant narrowing of their lumens. It differs from bronchiolitis obliterans-organizing pneumonia in its histopathology and clinical course. Most cases of CB occur in the setting of organ transplants, particularly lung and heart-lung transplants, but also in bone marrow transplants. Other bona fide cases are rare: infection, particularly viral infection, appears to be a well-documented precursor to CB in children, but not in immunocompetent adults. Constrictive bronchiolitis also has been reported in the course of rheumatoid arthritis, in certain other autoimmune diseases such as pemphigus vulgaris, after inhalation of toxic gases such as nitrogen oxide, after ingestion of certain drugs or medicinal agents such as Sauropus androgynous, and as a cryptogenic illness. Recent reports suggest that CB, as defined by clinical criteria (that is, bronchiolitis obliterans syndrome), is very common in lung allograft recipients who survive more than 5 years and, although it is associated with significant mortality, it also can be clinically stable. Furthermore, with the current practice of close monitoring of these patients, it appears that CB may now be diagnosed at an earlier stage, at which resolution, or at least stabilization of progression, is possible. A histopathologic diagnosis of CB in lung transplant and other patients may be difficult to make due to the patchy distribution of lesions, the technical difficulty in obtaining tissue in late lesions with extensive fibrosis, and the failure to recognize lesions. With regard to the last of these, in early stages of disease, CB may be subtle and easily missed in routine hematoxylin-eosin-stained specimens, while in advanced stages the disease may be equally difficult to diagnose if the patchy scarring in the lung is interpreted as nonspecific. The relative loss of bronchioles and the relationship of the scars to contiguous arteries should signal the need for elastic stains to look for the residual elastica of the bronchioles amidst the foci of fibrosis. Increasingly, clinical grounds, including pulmonary functions studies and high-resolution computed tomography findings, are proving to be relatively sensitive methods of detecting CB. Finally, the progressive airway destruction in chronic transplantation rejection appears to be a T-cell-mediated process. The "active" form of constrictive bronchiolitis, with attendant lymphocytic inflammation of the airways, likely precedes the "inactive" or scarred form of constrictive bronchiolitis.

Pleuro-pulmonary endometriosis and pulmonary ectopic deciduosis: a clinicopathologic and immunohistochemical study of 10 cases with emphasis on diagnostic pitfalls.

The clinical and pathological features of nine cases of pleuro-pulmonary endometriosis and the first case of pulmonary ectopic deciduosis are presented. The patients were all women between the ages of 27 and 74 years (median, 36 years) who presented with symptoms of catamenial pleural pain, shortness of breath, hemoptysis, or radiographically detected lung masses. Clinically, six patients were multiparous, one patient had pelvic endometriosis, and four patients had undergone prior pelvic surgical procedures, including dilatation and curettage. Radiographically, eight patients had pulmonary infiltrates or nodules, and four patients had pneumothorax. Three cases involved the visceral pleura and one case the parietal pleura. The other six cases, including the single case of ectopic deciduosis, involved the lung parenchyma. Histologically, the single or multifocal lesions were well circumscribed or infiltrative, nodular, cystic, or nodulo-cystic, and showed the characteristic features of proliferative or secretory endometrium with numerous mullerian metaplastic changes. Mucin stains were negative in five cases of endometriosis and in the single case of ectopic deciduosis. Immunohistochemical studies were performed in these same six cases using antibodies to epithelial, mesenchymal, vascular, and neuroendocrine markers. The glandular epithelium was decorated with antibodies to pan-cytokeratin, CK7, BER-EP4, ER, and PR, whereas the stromal cells showed positive staining for vimentin, actin, smooth muscle actin, desmin, ER, and PR. Follow-up information obtained in seven patients showed all women without recurrences after 1 to 20 years. The current study highlights the importance of recognizing intrathoracic endometriosis and ectopic deciduosis and properly assessing small biopsy specimens to avoid a misdiagnosis of malignancy.

Solitary pulmonary papillomas in adults: a clinicopathologic and in situ hybridization study of 14 cases combined with 27 cases in the literature.

Solitary endobronchial papillomas in adults are rare neoplasms. Only sporadic cases have been documented. The histologic classification of these tumors remains problematic, and little is known about their clinical behavior. The clinical and pathologic features of 13 endobronchial papillomas and a single endobronchiolar papilloma were reviewed. In situ hybridization for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/51 was performed on seven cases. Twenty-seven additional well-documented cases were identified in a literature review. Human papillomavirus studies were performed in four of the previously reported cases. The 41 neoplasms combined from the Armed Forces Institute of Pathology and literature review were divided into three groups according to their histologic features. Thirty-one of 41 (76%) patients were men. The ages of the patients ranged from 26 to 74 years (median, 57 years). Three morphologically distinct histologic types were recognized; 27 squamous cell papillomas, 7 glandular papillomas, and 7 mixed squamous and glandular papillomas. Squamous papillomas: 23 of 27 (85%) patients were men, and the median age was 54 years. Six of eleven (55%) of these patients smoked. Twenty-six lesions were exophytic and a single lesion had an inverted pattern. Seven of 24 (29%) lesions featured cytologic atypia and 5 of 24 (14%) had viral cytopathic effect. Five of seven (71%) cases examined for HPV DNA were positive. Three of 18 (17%) recurred. Glandular papillomas: Four of seven (57%) patients were women. The mean age was 67 years. One of five (20%) patients smoked. Five lesions were central, and two were peripheral. Four lesions had columnar epithelium, and three had ciliated epithelium. One of six (17%) lesions recurred. Mixed papillomas: five of seven (71%) patients were men. The median age was 64 years. Three of five (60%) patients smoked. Three of seven (43%) lesions featured cytologic atypia. Four of five lesions were examined for HPV DNA and all were negative. No lesions recurred. This study demonstrates that solitary endobronchial papillomas can be separated into three distinct morphologic categories. Squamous cell and mixed papillomas are predominantly lesions of male smokers in their 6th decade. Although cytologic atypia is observed in many cases, the rarity of these tumors and difficulty in separating papillomas from endobronchial papillary squamous carcinomas make generalizations regarding the risk of progression to carcinoma tenuous at best. Human papillomavirus appears to play a pathogenetic role in some squamous cell papillomas, but not in mixed papillomas, yet its presence in the squamous lesions does not correlate with recurrence or malignancy. The first report of an inverted squamous cell papilloma indicates clinical features similar to the more common exophytic squamous cell papillomas. Glandular papillomas, the rarest of all endobronchial papillomas, are found in an older age group than squamous and mixed papillomas, and most-patients are nonsmokers. Based on these findings, all endobronchial papillomas should be completely excised.