Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis.

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patient's kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.

Rhabdomyomatous thymoma.

A case of a thymic neoplasm with a prominent rhabdomyomatous component is presented. The patient, a 21-year-old asymptomatic man, had an anterior mediastinal mass found on routine chest radiographs. Surgical resection of an encapsulated anterior mediastinal mass was performed. Histologically, two distinct cell populations were apparent, one epithelial and the other myoid. Immunohistochemical studies using antibodies for keratin decorated the epithelial component of this lesion; antibodies for myoglobin and desmin strongly stained the myoid component.

Acinic cell carcinoma of the lung ("Fechner tumor"). A clinicopathologic, immunohistochemical, and ultrastructural study of five cases.

The clinical, pathological, immunohistochemical, and ultrastructural features in five cases of primary acinic cell carcinoma of the lung are presented. The patients' ages ranged from 44 to 75 years (mean, 56); four were women and one a man. The lesions were discovered incidentally on routine chest x-ray and ranged from 1.2 to 4 cm in greatest diameter. Three tumors were located in the right middle lobe, one in the right upper lobe, and one in the left upper lobe. In three cases, the lesions presented as asymptomatic subpleural nodules in proximity to secondary bronchi, one case presented as an endobronchial tumor that led to obstructive symptoms, and one case as a well-circumscribed deep parenchymal nodule. Histologically, the tumors were composed of clear cells with abundant granular cytoplasm growing as solid sheets with focal acinar, microcystic, and papillocystic areas. Immunohistochemical stains showed strong positivity of the tumor cells for low-molecular-weight cytokeratins and epithelial membrane antigen (EMA). Focal weak cytoplasmic positivity was observed in three cases with alpha-1-antichymotrypsin and in one case with amylase. Stains for vimentin, S-100 protein, chromogranin, and lysozyme were negative in all cases examined. Electron microscopy performed in four cases showed abundant zymogen-type cytoplasmic granules of variable electron density characteristic of acinar-type secretory cells. All patients were treated by lobectomy alone. Follow-up of 3 to 10 years in four cases revealed that all patients were alive and well, with no evidence of recurrence or metastases. Because of their relatively indolent behavior and favorable prognosis, primary acinic cell carcinoma of the lung must be distinguished from other primary and metastatic clear cell tumors of the lung.

Allergic granulomatosis (Churg-Strauss syndrome): pulmonary and renal morphologic findings.

The pulmonary histopathology of four cases of allergic granulomatosis (Churg-Strauss syndrome) was reviewed. Renal tissue was also studied in one case. The patients were young and most presented with asthmatic symptomatology. They showed marked peripheral blood eosinophilia, and had fluffy nodular pulmonary infiltrates by chest x-ray. Serum IgE was elevated in the one patient in whom it was obtained. The lung tissue in all cases showed necrotizing giant-cell vasculitis, interstitial and perivascular granulomas, and eosinophilic pneumonia-like areas. These microscopic features distinguish allergic granulomatosis from other forms of pulmonary eosinophilia or vasculitis. Renal tissue showed necrotizing granulomatous vasculitis and interstitial eosinophilic nephritis, without evidence of glomerulonephritis. Electron-microscopic study of one lung biopsy and of the renal tissue demonstrated tissue eosinophilia and, in lung, a granuloma. There was no evidence of vascular or glomerular electron-dense deposits. These findings are discussed in the light of possible pathogenetic mechanisms of allergic granulomatosis.

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.

Epithelioid hemangioendothelioma of the anterior mediastinum. Clinicopathologic, immunohistochemical, and ultrastructural analysis of 12 cases.

Twelve cases are reported of primary epithelioid hemangioendothelioma of the anterior mediastinum. Patient ages ranged from 19 to 62 years (mean, 49.4); three were women and nine were men. Seven patients presented with symptoms due to compression of surrounding structures; the remainder were asymptomatic and the lesions were discovered on routine chest x-ray films. The tumors measured from 4.5 to 13.5 cm in greatest diameter; they were encapsulated and well-circumscribed in seven cases and locally infiltrative in five. Histologically, a spectrum of features was observed ranging from those classically described for low-grade epithelioid hemangioendothelioma at other locations--including cells with abundant eosinophilic cytoplasm showing prominent vacuolization and intracellular lumen formation, few mitotic figures, and myxoid changes in the stroma--to more pronounced cytologic atypia, increased mitotic activity, and areas of necrosis. Metaplastic bone formation and osteoclast-type giant cells were observed in five cases, and four tumors displayed focally a prominent intravascular papillary endothelial component. Immunohistochemical studies showed positive staining of the neoplastic cells with factor VIII-related antigen and vimentin and focal staining in most cases with Ulex europaeus lectin. Stains for broad-spectrum keratin, CAM-5.2, S-100 protein, CD34, actin, and desmin were negative. Electron microscopic examination in three cases showed features distinctive for epithelioid vascular endothelial cells, including abundant cytoplasmic intermediate filaments, basal lamina material, marked pinocytotic activity, and primitive intracytoplasmic lumen formation. All cases were treated by surgical excision. Follow-up information was available in nine patients; seven patients were alive and well without evidence of disease 2-21 years after diagnosis (mean follow-up, 8 years); one patient had a recurrence after 1 year and died due to complications of surgery, and another patient died after 1 year of undetermined causes. Despite their often ominous clinical, radiological, and pathological features, epithelioid hemangioendotheliomas arising in the anterior mediastinum appear to behave as low-grade malignant neoplasms that may be adequately controlled in most instances by surgery alone.

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 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.

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.

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.

Thymomas presenting as pleural tumors. Report of eight cases.

Eight cases of thymomas presenting as pleural-based lesions are presented. The patients are five men and three women between the ages of 38 and 71 years (mean 54.5). Histologically, six tumors showed morphologic features indistinguishable from classical mediastinal thymomas, namely lobulation produced by fibrous bands and a biphasic cell population composed of epithelial cells admixed with small lymphocytes. One case showed prominent spindle cell configuration and marked vascularization resulting in a hemangiopericytomalike appearance; in another case, the epithelial component was associated with cystic structures. The radiographic findings were diffuse pleural thickening with encasement of the lung in four cases; an ill defined mass involving the right diaphragmatic pleura with engulfment of the left lower lobe in one case; diffuse pleural thickening along the mid lateral axillary line in one case; and left-sided pleural masses involving the diaphragmatic and chest wall pleural surfaces in another. In the remaining case, a massive unilateral left pleural effusion obscured the underlying lesion. Clinically, the patients presented with varied symptoms, including shortness of breath, fever, and weight loss. Follow-up information was obtained in four patients. One patient died 1 month after initial diagnosis, but no details of the cause of death were available. Another had metastasis to the groin 1 year after diagnosis. The other two patients were alive and well 2-10 years after the initial diagnosis.

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.

Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid.

Neuroendocrine tumors of the lung embrace a spectrum from low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), and high-grade categories of large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC). We studied 200 neuroendocrine lung tumors to critically evaluate the Arrigoni histologic criteria for AC using statistical analysis to delimit more rigorously an intermediate survival for AC between TC and the high-grade tumors of LCNEC and SCLC. Histologic features that might predict prognosis were used for Kaplan-Meier and Cox proportional hazards survival analysis, and an optimal mitotic range for AC was calculated. The optimal mitotic range for AC was 2 to 10 mitoses per 2 mm2 of viable tumor (10 high-power fields). Based on this finding, we collapsed mitoses into three categories (< 2; 2-10; > or = 11) and performed Cox multivariate analysis for all 200 neuroendocrine tumors. Mitotic counts were the only independent predictor of prognosis. Based on this analysis, we propose that AC be defined as a tumor with neuroendocrine morphology, mitotic counts between 2-10 per 2 mm2 of viable tumor (10 high-power fields), or coagulative necrosis. Using these criteria, the 200 neuroendocrine tumors were classified as 51 TC, 62 AC, 37 LCNEC, and 50 SCLC. The 5- and 10-year survival was 87% and 87% for TC, 56% and 35% for AC, 27% and 9% for LCNEC, and 9% and 5% for SCLC, respectively. After stratification for stage, survival for AC was significantly worse than for TC (p < 0.001); for LCNEC and SCLC it was significantly worse than for AC; but the survival for LCNEC was no different than that for SCLC.

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.

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.

Proliferation and cellular phenotype in lymphomatoid granulomatosis: implications of a higher proliferation index in B cells.

Pulmonary involvement by lymphomatoid granulomatosis (LYG) is characterized by nodules of a polymorphous lymphoreticular infiltrate with necrosis, angioinvasion, and variable numbers of large, atypical cells. Using combined immunohistochemistry, the authors compared the expression of a marker of proliferation (DNA topoisomerase IIalpha) between B cells, T cells, and histiocytes. Sixteen cases of LYG were stained by combined immunohistochemistry for DNA topoisomerase IIalpha and CD-20, CD-3, CD-68, and CD-57. A proliferation index was determined for B cells, T cells, histiocytes, and natural killer cells by dividing the number of cells with coexpression of DNA topoisomerase IIalpha and CD-20, CD-3, CD-68, or CD-57 by the total number of CD-20+, CD-3+, CD-68+, or CD-57+ cells, respectively. A significantly higher proliferation index was present in B cells compared to T cells, histiocytes, or natural killer cells (p < 0.002). The average proliferation index for B cells was 0.25+/-0.24 (range, 0.00-0.76), for T cells was 0.02+/-0.01 (range, 0.00-0.04), for histiocytes was 0.00+/-0.01 (range, 0-0.02), and for natural killer cells was 0.00+/-0.00 (range, 0.0-0.02). The average proliferation index of CD-20+ cells was greater in grade III LYG (0.36) than in grade II LYG (0.17) or the single case of grade I LYG (0.00). The authors conclude that (1) there is a spectrum of B-cell proliferation in LYG that roughly correlates with histologic grade, (2) T cells, histiocytes, and natural killer cells do not proliferate but are recruited, and (3) the average B-cell proliferation index in grade III LYG is similar to that observed in large cell non-Hodgkin's B-cell lymphomas. These observations provide a possible rationale for the use of chemotherapy for grade III LYG and observation or immunologic adjuvants for LYG with grade I or grade II histology.

Hepatic amyloidosis: morphologic differences between systemic AL and AA types.

The liver is almost universally involved in systemic amyloidosis. Patterns of topographic distribution of amyloid within the liver lobule have been recognized, but the reliability of using these for classification of amyloid type is in question. We examined 286 livers from cases of systemic amyloidosis obtained from autopsies at Los Angeles County-University of Southern California Medical Center, classifying them as AL or AA type by means of the potassium permanganate Congo red-staining method along with a specific anti-AA antiserum. Prior publications have asserted that deposition of secondary (AA) amyloidosis is limited to the vessels in the portal tract, constituting a "vascular" pattern, and that in primary (AL) amyloidosis the deposits exhibit a "sinusoidal" pattern in that they are seen along hepatic sinusoids as well as in portal vessels. We confirmed that AL amyloid involves the portal vessels as frequently as AA amyloid and that deposition occurred significantly more frequently in the portal stroma, the central vein, and the "sinusoidal" areas. However, we also found a "sinusoidal" pattern in 29 of 78 cases of secondary (AA) amyloidosis; in 14 of these, more than half of the sinusoidal spaces were replaced by amyloid deposits. We also noted that in 23 of the 29 AA amyloidosis cases with "sinusoidal" involvement, a "sago" pattern of distribution of amyloid in the spleen was present. No consistent association of a specific chronic inflammatory disease with "sago" spleen and "sinusoidal" deposits could be documented. We conclude that topographic distribution of amyloid within the liver lobule is not a reliable method of distinguishing AA from AL amyloidosis and that specific staining methods must be used if the physician is to be able to attempt modern therapeutic modalities.

Mutations in the p53 gene in pulmonary blastomas: immunohistochemical and molecular studies.

Well-differentiated fetal adenocarcinomas and biphasic blastomas are types of lung cancer that contain glands that mimic the appearance of fetal lung. Biphasic blastomas also show a primitive embryonic stroma. Despite histological similarities leading these two tumors to be classified as pulmonary blastomas, they have distinct clinical and prognostic features. Little information is available on genetic changes in these tumors because they are rare; therefore, the authors studied nine biphasic blastomas and 12 well-differentiated fetal adenocarcinomas for the presence of mutations in the p53 gene. Mutations in the p53 gene are common in other lung cancers, and the type of mutation in the p53 gene can provide information about the original or inciting mutagens. The authors found five biphasic blastomas (42%) had mutations in the p53 gene by immunohistochemical and molecular analysis, whereas none of the well-differentiated fetal adenocarcinomas contained mutations. These results provide molecular support for the significance of distinguishing between well-differentiated fetal adenocarcinoma and biphasic blastoma histologically and identify several types of p53 gene mutations that occur in these tumors.

Pulmonary blue bodies.

Pulmonary blue bodies are intra-alveolar laminated basophilic concretions of uncertain etiology. Blue bodies were studied in lung biopsy specimens from 10 patients. The patients ranged in age from 47 to 69 years and were predominantly men. Three had a history of overt exposure to environmental dusts such as sawdust and asbestos, and two showed occasional ferruginous bodies in the lung, raising the possibility of pneumoconiosis. In eight cases there was interstitial pneumonitis, which resembled desquamative interstitial pneumonia by light microscopy but which was often seen to be patchy and asymmetrically distributed in the lung by chest x-ray examination. Of two other patients, one had xanthogranulomatous inflammation and the other, necrotizing granulomatous inflammation. Light and electron microscopic, histochemical, microchemical, and x-ray diffraction studies of blue bodies were also performed. Calcium carbonate is a major component of blue bodies and is responsible for their birefringence in unstained sections and ready solubility in acid solutions. Blue bodies also contain a mucopolysaccharide matrix and iron. We offer the hypothesis that blue bodies (calcium carbonate) are a product of histiocytic catabolism.