Toshimasa Uekusa

Lymphangiogenesis in Lymphangioleiomyomatosis Its Implication in the Progression of Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is characterized by the proliferation of abnormal smooth muscle cells (LAM cells) in the lungs, lymph nodes, and/or other organs. We examined lymphangiogenesis using immunohistochemistry for Flt-4 (VEGFR-3), a new specific marker for lymphatic endothelial cells, as well as the expression of vascular endothelial growth factor (VEGF)-C in LAM. Specimens were obtained from 6 autopsy cases, a single lung transplant case, and 8 surgical cases for analyses. We demonstrated that lymphatics were extremely abundant in both pulmonary and extrapulmonary LAM and that lymphatic endothelial cells not only proliferated encompassing LAM foci but also infiltrated the intra-LAM foci, and that in advanced LAM, lymphangiogenesis involved vascular walls and interstitium surrounding the area where LAM cells proliferate. In contrast, angiogenesis, confirmed with CD31 immunostaining, was observed less in the LAM foci. LAM cells demonstrated positive reactivity against anti-VEGF-C antibody at varying intensities. Significant correlation (P < 0.001) was noted between the degree of lymphangiogenesis in LAM or VEGF-C expression on LAM cells and lymphagioleiomyomatosis histologic score (LHS), which represents the histologic severity of pulmonary LAM and has been reported to have prognostic significance. Our study is likely to provide a novel point of view on the pathophysiologic significance of lymphangiogenesis in LAM.

The lung in polyarteritis nodosa: A pathologic study of 10 cases

Polyarteritis nodosa (PAN) is characterized by necrotizing arteritis of medium-sized and small arteries in various organs. Pulmonary artery involvement in PAN has been considered rare. Previously, it also has been thought that patients with PAN do not have interstitial pneumonitis and fibrosis. A detailed pathologic analysis of pulmonary diseases associated with PAN was made in 10 autopsy cases of PAN. Arteritis affecting bronchial arteries was present in seven patients (70%). The data obtained suggest that arteritis in the lung in patients with PAN is more common than has been recognized previously. Diffuse alveolar damage (DAD) involving all lobes bilaterally was present in five patients; it was acute in two patients and organizing in three. In the patients with organizing DAD the degree of fibrosis in the interstitium differed among the lobes, and the fibrosis was more severe in the lower lobe than in the other lobes. Two patients presented with interstitial fibrosis with honeycomb lung of the posterior and lateral basal segments of the lower lobes of both lungs; in one of these patients interstitial fibrosis was present in an area of organizing DAD. Five patients died of respiratory failure resulting from DAD. In conclusion, it is important to consider DAD and interstitial fibrosis as complications of PAN.

Primary pulmonary adenocarcinoma with enteric differentiation resembling metastatic colorectal carcinoma: a report of the second case negative for cytokeratin 7.

We report the case of a 51-year-old woman with pulmonary adenocarcinoma with enteric differentiation (PAED) that is indistinguishable from metastatic colorectal carcinoma by immunohistochemistry as well as histology. A chest computed tomography scan revealed a 1cm nodule in the right upper lobe and a 3cm mass in the left lower lobe. Initial examination showed no evidence of any other tumor. She underwent partial resection of the right upper lobe and left lower lobectomy. Histopathological examination revealed that both tumors were composed of medium to large complex glands with central necrosis. The tumor cells were cuboidal to tall columnar with eosinophilc cytoplasm, oval nuclei, and brush-border. Immunohistochemical study yielded the following results: tumor cells were diffusely positive for cytokeratin (CK) 20 and CDX-2, and negative for CK7, thyroid transcription factor-1, and Napsin A. MUC2 was partially observed, while MUC5AC was not detected. These findings were strongly indicative of metastatic colorectal carcinoma. However, no primary colorectal cancer was detected in any clinical examination, including fluorine 18-labeled fluorodeoxyglucose-positron emission tomography scan and video capsule endoscopy, and she has not presented with any characteristic symptoms at any follow-up to date, approximately 4 years after operation. From all features, the final diagnosis was primary PAED, suggestive of multifocal primary lung cancer. So far, only 1 case of CK7-negative PAED has been reported. This is the second case of primary PAED resembling metastatic colorectal cancer morphologically and immunohistologically.

Methotrexate-associated lymphoproliferative disorders mimicking angioimmunoblastic T-cell lymphoma

Patients affected by autoimmune diseases (rheumatoid arthritis (RA), psoriasis, and dermatomyositis) treated with methotrexate (MTX) develop lymphoproliferative disorders (LPDs). These cases have been reported to be diffuse large B-cell lymphoma, Hodgkin lymphoma, or polymorphous post-transplant LPDs. However, angioimmunoblastic T-cell lymphoma (AITL) is extremely rare in the medical literature. In this report, we describe three cases of RA patients who developed MTX-associated LPDs resembling AITL. They developed systemic lymph node swelling after initiation of MTX. The affected lymph nodes showed the histological finding of AITL: polymorphous infiltrates, mainly T-cells and arborizing high endothelial venules. Two cases showed a predominance of CD4-positive cells in proliferative T-cells, whereas the third case showed CD8-positive cells. CD10 was negative in all cases. RNA in situ hybridization of Epstein-Barr virus (EBV) demonstrated EBV-positive B-cells to be scattered in two cases, but not in one case. The lymphoadenopathy spontaneously regressed with cessation of MTX in all three cases, but one case recurred. These are interesting cases of MTX-associated LPDs mimicking AITL, and cessation of MTX is the only cure for patients with MTX-associated LPDs resembling AITL.

Pulmonary sarcoidosis and antiphospholipid syndrome.

Abstract:  Various autoimmune diseases have been reported to occur in patients with sarcoidosis. However, coexistence of sarcoidosis and antiphospholipid syndrome (APS) is extremely rare. We describe a 59‐year‐old female patient with pulmonary sarcoidosis who had preceding APS. Her previous medical history consisted of a miscarriage and ischemic colitis. She was diagnosed as APS during the onset of a brainstem infarction with positive reaction to β2‐glycoprotein I‐dependent anticardiolipin antibody. Two years later, chest CT revealed enlargement of the hilar and mediastinal lymph nodes and small nodules in the lung fields. Transbronchial lung biopsy demonstrated non‐caseating epithelioid cell granuloma leading to the diagnosis of definite pulmonary sarcoidosis. This is the first APS case where pulmonary involvement with sarcoidosis has been confirmed through lung biopsy. Our case report suggests that APS should be recognized as an accompanying disorder of sarcoidosis.

Plasmablastic lymphoma of the cecum: report of a case with cytologic findings.

Plasmablastic lymphoma (PBL) is a rare lymphoma that is characterized by a diffuse proliferation of large neoplastic cells resembling B immunoblasts, but shows the immunophenotype of plasma cells. PBL is most commonly seen in the oral cavity of human immunodeficiency virus (HIV)‐positive patients. Epstein‐Barr virus (EBV) may be closely related the pathogenesis of PBL. We report a case of HIV‐negative PBL in a 75‐year‐old man without EBV infection. Histologic examination of the cecal tumor following right hemicolectomy and cytologic examination of ascitic fluid were performed. Cytologic specimens were hypercellular and composed of single cells and loosely formed clusters. Large tumor cells showed plasmacytoid features with basophilic cytoplasm, large nuclei, prominent nucleoli, and focal perinuclear halos. Abnormal mitotic figures were easily identified. On immnohistologic study, the tumor cells were positive for CD138 (plasma cell marker) and kappa, but negative for CD45, CD3, CD20, CD79a, CD56, and cyclin D1. The proliferation index (Ki‐67) was high. This is a very rare case of PBL without HIV and EBV infection, involving the cecum. Diagn. Cytopathol. 2011;39:297–300.

Possibility of lanthanum absorption in the stomach

Lanthanum carbonate (LC) is an orally administered phosphate binder. Its absorption is generally thought to be minimal. We report here the case of an 81-year-old woman who underwent subtotal gastrectomy for gastric cancer after receiving hemodialysis for 1 year and taking LC for 7 months. Lanthanum phosphate compounds were found histologically in the gastric mucosa and a regional lymph node and confirmed by scanning and transmission electron microscopy–energy-dispersive X-ray spectroscopy. These findings suggest that lanthanum is absorbed in the stomach and transported via lymph flow. This observation could prove helpful in future investigation of lanthanum disposition.

Histopathological bronchial reconstruction of human bronchiolitis obliterans

To clarify the morphological mechanisms of airway obliteration in bronchiolitis obliterans (BO) associated with various causes, we conducted a retrospective study of 9 patients with a histological diagnosis of BO. The morphological characteristics were analyzed by histopathological bronchial reconstruction. BO was classified into two major morphologic subtypes: constrictive BO (CoB) and cellular/destructive BO (CDB). CoB is characterized by concentric narrowing of the airway lumen due to submucosal fibrosis. In contrast, in CDB the narrowing of the airway lumen is due to intraluminal, mural, and peribronchiolar infiltration of inflammatory cells as well as proliferation of granulation tissue. The histopathological diagnosis was CoB in 6 patients and CDB in 3 patients. Macroscopic bronchial reconstruction in CoB demonstrated that the beginnings of bronchial obliterations were in the 4th to 7th branches, numbering from each segmental bronchus and the lesions were distributed intermittently. Histopathologically, the localization of obliteration was mainly from small bronchi to membranous bronchioli with intermittent airway luminal obliteration in CoB, whereas the primary lesions in CDB revealed more continuous obliteration of the bronchiolar lumen than observed in CoB. In conclusion, this bronchial reconstruction study demonstrated marked morphological differences in the mechanisms of airway obliteration between two major morphologic subtypes of BO.

Bronchiolitis obliterans associated with Stevens-Johnson Syndrome: histopathological bronchial reconstruction of the whole lung and immunohistochemical study

This study presents an extremely rare case of constrictive bronchiolitis obliterans (BO) associated with Stevens-Johnson Syndrome (SJS) provides the morphological and immunohistochemical features using histopathological bronchial reconstruction technique. A 27-year-old female developed progressive dyspnea after SJS induced by taking amoxicillin at the age of 10. Finally, she died of exacerbation of type II respiratory failure after 17 years from clinically diagnosed as having BO. Macroscopic bronchial reconstruction of the whole lungs at autopsy showed the beginning of bronchial obliterations was in the 4th to 5th branches, numbering from each segmental bronchus. Once they were obliterated, the distal and proximal bronchi were dilated. Microscopic bronchial reconstruction demonstrated the localization of obliteration was mainly from small bronchi to membranous bronchioli with intermittent airway luminal narrowing or obliteration. Moreover, CD3-, CD20-, and CD68-positive cells were found in the BO lesions. CD34- and D2-40-positive cells were mainly distributed in the peribronchiolar lesions and bronchiolar lumens, respectively. SMA- and TGF-β-positive cells were seen in the fibrous tissue of BO lesions.The virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1071703140102601.

Collision tumor of primary malignant lymphoma and adenocarcinoma in the colon: report of a case.

This report presents the case of a 62-year-old man with a collision tumor of primary malignant lymphoma and adenocarcinoma in the cecum. All regional mesenteric lymph nodes that were removed surgically were found to be occupied by lymphoma cells and no lymph nodes contained any cancer cells, although the primary carcinomas did exhibit lymphatic invasion. Malignant lymphoma was also seen in the duodenum. Systemic chemotherapy was administered for the malignant lymphoma, and a complete response was thus obtained. However, just after chemotherapy multiple liver metastases of adenocarcinoma emerged, and chemotherapy against adenocarcinoma was therefore continued. The occurrence of synchronous lymphoma and adenocarcinoma of the colorectum is rare. Furthermore, collisions of these different entities are also extremely unusual; so far only five such case reports have been published. The accurate clinical determination of the dominant tumor and a close follow-up is required for proper treatment in these cases.