Masaru Oritsu

Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia

Takemura T, Akashi T, Kamiya H, Ikushima S, Ando T, Oritsu M, Sawahata M & Ogura T 
(2012) Histopathology
Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia

Pulmonary vascular involvement in sarcoidosis: granulomatous angiitis and microangiopathy in transbronchial lung biopsies.

To evaluate the occurrence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis, transbronchial lung biopsy specimens were examined from 174 cases with sarcoidosis. Granulomatous angiitis was seen in 72 cases, which corresponded to 53% of the cases with granulomata. Granulomatous angiitis showed venous involvement (65%), both venous and arterial involvement (24%) or arterial involvement only (11%). There was no significant difference in occurrence of granulomatous angiitis between upper and lower lobes. The cases with granulomatous angiitis in the lung had a higher frequency of ophthalmic symptoms and elevated serum angiotensin converting enzyme level. Basal lamina layering in the microvasculature was more often observed in the bronchial mucosa than in the alveolar walls and is not exclusively related to granulomata. Endothelial proliferation and basal lamina alterations in granulomatous angiitis may be closely associated with granulomas. The present study revealed coexistence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis and suggests that both may participate in the development of pulmonary sarcoidosis.

Hyperplastic epithelial foci in honeycomb lesions in idiopathic pulmonary fibrosis

Abstract. Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973–1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect.

Telomerase Activity Significantly Correlates with Chromosome Alterations, Cell Differentiation, and Proliferation in Lung Adenocarcinomas

Telomerase activity was examined by the telomeric repeat amplification protocol assay in 25 cases of lung adenocarcinoma, in relation to cancer cell differentiation, proliferation, and chromosome alterations. Telomerase activity, chromosome alterations, and cell proliferation assessed by Ki-67 labeling were significantly lower (P < .001 to .05) in well-differentiated (10 cases) than in moderately differentiated (8 cases) or poorly differentiated (7 cases) lesions. Telomerase activity by semiquantitative analysis with scoring of 0 to 3 was significantly correlated with similarly graded chromosome alterations (P < .05) and Ki-67 labeling indices (P < .002). Telomerase activity and chromosome alteration (T-C) indices generated by multiplication of telomerase activity and chromosome alteration scores also showed a significant correlation with cell differentiation. The Clara cell subtype, confirmed by electron microscopic analysis, significantly predominated in the well-differentiated group, showing a low grade of telomerase activity and chromosome alterations and low Ki-67 labeling indices, suggesting clinical relevance. No significant association of telomerase activity was found with p53 protein accumulation or Bcl-2 protein expression. The good correlation of telomerase activity with chromosome alterations, cell differentiation, and Ki-67 labeling indices suggests that this parameter might have potential application in estimation of prognosis.

VASCULAR INVOLVEMENT IN CUTANEOUS SARCOIDOSIS

Sarcoldorls is a systemlc granulomatous disease with systemic vascular Involvement, that Is, granulomatous anglitis and mieroanglapathy. To detarmlne if there is vascular Invoivement In cutaneous sarcoidosls, we examined 42 skin specimens taken from 32 patients with cutaneous lesions of narcoidosls. Cutaneous sarcoidosis was prevalent In older females with high serum anglotensin‐converting enzyme (ACE) levels. Most skin lesions appeered during the following up of narcoldosis. Granulomatous anglitls was present in 12 specimens of sarcold skin lesions (30.8%). Eight of the 12 specimens showed venous Involvement In the dermis. There was no correlation between the Incldence of granulomatous anglitis and the gross pattern of cutaneous sarcoldosls. Immunohistochemically, thrombomodulln was negative in the vascular endothelium close to the granuloma or a peri‐phlebltis lesion. Electron mlcroscopy revealed endothelial swelling, Iumlnal narrowing, and basal Iamina Iayering of the basement membrane in the capillaries and venules in the dermis. These findings demonstreted that granulomatous anglitis and mictoanglopathy coexist in cutaneous sarcoldosis.

Pulmonary tuberculosis with unusual cystic change in an immunocompromised host

We present a rare case of upper zone cystic change of the lung with disseminated tuberculosis of a non‐smoking 30‐year‐old immunocompromised male. He suffered from repeated pneumothorax. The basic pathological feature of video‐assisted thoracoscopic lung biopsy revealed granulomatous involvement in the respiratory bronchioles with poorly developed epithelioid cells and disruption of elastic fibers. Electron microscopy demonstrated a decrease in elastic fibers and disruption of the epithelial basement membrane of the respiratory bronchiole and no Langerhans cells in the lesion. Autopsy of the lung revealed centroacinar distribution of multiple cystic lesions in the bilateral upper lobe. Almost all cystic walls showed loss of elastic fibers and cysts frequently involved the respiratory and terminal bronchioles, alveolar ducts and, occasionally, alveoli. Some larger cystic lesions revealed communication to the bronchi. The cystic changes in this case of pulmonary tuberculosis may be caused by a check‐valve mechanism due to granulomatous involvement of the bronchioles and also by excavation of caseous necrotic material by draining bronchi.

Detection of antibodies to Borrelia species among patients with confirmed sarcoidosis in a region where Lyme disease is nonendemic

Abstract• Background: Lyme disease is a multisystemic disorder caused by the spirochete Borrelia burgdorferi, while sarcoidosis is a multisystemic granulomatous disease of unknown etiology. The purpose of this study was to evaluate the relationship between Lyme disease and sarcoidosis. • Methods: We examined the seroprevalence of antibody to Borellia species in patients with sarcoidosis. We performed the enzyme-linked immunosorbent assay, using three Japanese Borrelia species in addition to B. burgdorferi, and dotblot analysis using purified Borrelia-specific proteins in 38 patients with histopathologically confirmed sarcoidosis and 80 healthy controls. • Results: Two patients (5.3%) were positive for antibodies to Borrelia species according to one or both assays, and one (1.2%) healthy control was positive. In both patients it was suspected that Borrelia infection had developed prior to the development of sarcoidosis. • Conclusion: Borrelia species were thought not to be responsible for the development of sarcoidosis in a nonendemic region in Japan.Since clinical manifestations of Lyme disease share certain similarities with those seen in sarcoidosis, ophthalmologists should be aware of the need to differentiate between the two diseases and the need for prompt treatment in each case.

Bilateral neovascular glaucoma due to multicentric Castleman disease

We immediately discontinued the administration of latanoprost and started application of topical diclofenac sodium four times daily. Four months later, visual acuity in his right eye improved from 0.7 to 1.2, and the micropsia disappeared. Although the retinal capillary telangiectasis was essentially unchanged, slit-lamp biomicroscopic fundus examination showed that the macular edema was improved, and OCT showed a decrease in the retinal thickness (Fig. 2B).