Pulmonary Chemodectomas Research Articles

DIFFUSE PULMONARY MENINGOTHELIOMATOSIS DIAGNOSED BY TRANSBRONCHIAL CRYOBIOPSY

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Minute pulmonary meningothelial-like nodules (MPMNs) are typically asymptomatic, solitary lesions incidentally noted on pathologic evaluation of lung tissue. However, diffuse, bilateral pulmonary involvement, termed diffuse pulmonary meningotheliomatosis (DPM), is exceedingly rare and has only been described in a small number of case studies. We report a case of a patient diagnosed with DPM via transbronchial cryobiopsy. CASE PRESENTATION: A 67-year-old non-smoking female with a history of scleroderma was referred for diffuse bilateral pulmonary nodules found on computed tomography (CT) scan of the chest with mosaicism concerning for diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). Pulmonary function testing was notable for an isolated reduction in diffusing capacity at 58% with a normal echocardiogram. Two transbronchial cryobiopsy samples were obtained from the right lower lobe. Pathology revealed a meningothelial nodule. Immunohistochemistry was positive for epithelial membrane antigen (EMA) as well as progesterone receptor (PR) and negative for synaptophysin and chromogranin. Follow up imaging at 1 year demonstrated stability. Taken in context with her radiographic findings, the patient was diagnosed with DPM. DISCUSSION: DPM is an extremely rare condition characterized by MPMNs diffusely involving lung parenchyma. It predominantly affects females (2.2:1) with a median age of 59-62. DPM has no predilection for specific lobes, and it can be mistaken for metastatic or interstitial disease. Histologically, MPMNs appear as epithelioid cells arranged in small nests in pulmonary interstitium. Immunochemically, MPMNs tend to be positive for vimentin, EMA and PR and negative for S-100 protein, chromogranin A, and synaptophysin. Though the clinical significance of DPM is still unclear, prior studies have noted higher incidence among patients with underlying lung disease, particularly thromboembolism and malignancy. CONCLUSIONS: In summary, we present a case of DPM diagnosed by transbronchial cryobiopsy to highlight the importance of considering DPM in the differential of bilateral micronodular lung disease. Reference #1: Korn D, Bensch K, Liebow AA, Castleman B. Multiple minute pulmonary tumors resembling chemodectomas. Am J Pathol. 1960;37(6):641–672. Reference #2: Gaffey MJ, Mills SE, Askin FB. Minute pulmonary meningothelial-like nodules. A clinicopathologic study of so-called minute pulmonary chemodectoma. Am J Surg Pathol 1988; 12: 167-175. Reference #3: Gleason JB, Valentin R, Almedia P, Martinez N, Bejarano PA. Diffuse pulmonary meningotheliomatosis: a literature review of a rare diffuse parenchymal lung disease with unclear clinical significance. J Assoc Chest Physic 2017; 5: 18-25. DISCLOSURES: Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim Pharmaceuticals Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Vapotherm, Inc Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria No relevant relationships by I. Obi Emeruwa, source=Web Response No relevant relationships by Scott Oh, source=Web Response No relevant relationships by Megan Trieu, source=Web Response

A case report on pulmonary chemodectoma

A 36-year old female patient was admitted to our hospital in October 2005, with symptoms of cough and phlegmatic stagnation plus chest distress for over 5 months. She had received an X-ray examination at a local hospital before her hospitalization, and it was shown that there was a small round-like pulmonary focus. No improvement was found after a pre-antiinflammatory treatment for the cough. CT scans showed that there were extensive nodular foci in both lungs, most of which were found in the inferior lungs. A shadow with multiple nodi could be seen in the mediastinum, with a likely possibility of metastatic lung carcinoma. A CT-guided right-lung puncture biopsy was conducted with the pathologic evidence revealing some tumor tissue (Fig.1). Immunohistochemical results indicated that homomorphic adenocarcinomas markers of the lung and kidney were expressed in the tumor cells, however, there was a strong expression of CgA, a neuroendocrine marker. The diagnosis was a pulmonary paraganglioma. One course of Taxotere chemotherapy with 120 mg d 1+cisplatin 100 mg d 2~4 was applied, and at the same time, Weimaining and thymopentin were administered plus symptomatic treatment of the cough. The patient was discharged form the hospital with improvement of her cough, without further follow-up.

Immunohistochemical and clonal analysis of minute pulmonary meningothelial-like nodules

The histogenesis of meningothelial-like nodule or so-called minute pulmonary chemodectoma remains unclear, with various immunohistochemical analyses giving inconsistent results. We performed an immunohistochemical and clonal analysis of minute pulmonary meningothelial-like nodules. Thirty-one histologically defined meningothelial-like nodules in 14 cases were stained immunohistochemically. One case had multiple lesions with brown pigment granules, which were positively stained with Berlin blue method, indicating the presence of hemosiderin. All meningothelial-like nodules were positive for vimentin and epithelial membrane antigen (EMA), but not for S-100 protein, chromogranin A, or synaptophysin. Five of 13 cases (13 of 28 lesions) were positive for CD68 by KP-1. Ten cases (24 lesions) stained for CD68 by PG-M1 were weakly positive. All lesions were negative for lysozyme, myosin, actin, keratin, and melanoma-associated antigen. Alveolar macrophages were intensely positive for CD68 and lysozyme in all examined cases. We analyzed the clonality of 11 minute pulmonary meningothelial-like nodule lesions in two female cases based on an X-chromosome—linked polymorphic marker, the human androgen receptor gene ( HUMARA). The HUMARA was found to be amplified with or without prior digestion by the methylation-sensitive restriction endonuclease HpaII. Six of 11 lesions showed monoclonal expansion. Five lesions in a multiple case showed different patterns of monoclonality. Our findings showed that minute pulmonary meningothelial-like nodules have meningothelial-like and phagocytic characteristics but no muscular phenotype. Furthermore, some minute pulmonary meningothelial-like nodules may show monoclonal expansion, whereas others are polyclonal. Our data indicate that minute pulmonary meningothelial-like nodules are reactive rather than neoplastic.

Multiple Pulmonary Chemodectomas in a Child

Chemodectomas (or paragangliomas) are rare tumors of neuroendocrine chemoreceptors, such as the carotid body. This report describes a case of multiple pulmonary chemodectomas in an adolescent and discusses the results of four therapeutic regimens. At 15 years of age, the patient had cough and fatigue. Investigation revealed numerous 1- to 2-cm diameter nodules throughout both lungs. Biopsy revealed multiple pulmonary chemodectomas of uncertain malignant potential. No extrapulmonary primary site could be found. Because of deteriorating pulmonary function, she was treated with courses of etoposide-cisplatin and subsequently somatostatin without effect. She finally responded to a course of doxorubicin and streptozocin. She is currently maintained on interferon-alpha 2B but her measured vital capacity continues to fall slowly, reflecting increased tumor growth. Because there is still no evidence of extrapulmonary spread, she is considered to be a candidate for lung transplantation. A doxorubicin-streptozocin combination produced a temporary remission of this patient's multiple pulmonary chemodectomas.

So-called minute chemodectoma of the lung

So-called minute pulmonary chemodectoma is a curious, small lung tumour found mainly in women. The nature and origin of the proliferating cells are still obscure. In the first report on the tumour, the component cells were described as resembling chemoreceptor cells and the tumour was named chemodectoma. However, electron microscopic studies of the tumour have revealed no evidence of neuronal characteristics and have shown a close resemblance to meningothelial cells. In this study, the electron microscopic findings were similar to those previously reported but in one of the two cases, tumour cells were filled with abundant cytofilaments, giving them an occasional dense, patch-like appearance. Immunostaining for myosin and vimentin was positive in all tumour cells, but epithelial membrane antigen staining was not seen. These findings indicate that the tumour might have its origin from muscle cells.

Minute pulmonary meningothelial-like nodules. A clinicopathologic study of so-called minute pulmonary chemodectoma.

The clinicopathologic features of 23 so-called minute pulmonary chemodectomas from nine patients are presented. Eight patients were women and one was a man; age range was 34-75 years (mean, 61). Two specimens were surgical resections and seven were autopsies (incidence, one per 60 autopsies). There was no association with a specific disease process or pathologic condition. Grossly, the lesions were 1-3 mm, tan to yellow, pleural or parenchymal nodules. Six of nine cases had multiple lesions; upper lobes were more often involved. Microscopically, characteristic cell nests expanded alveolar septa. Larger lesions were connected by intervening collagen, often imparting a stellate configuration. Smaller lesions had closely apposed nests with mildly thickened alveolar septa. The nodules were strongly reactive for epithelial membrane antigen (12 of 14) and vimentin (10 of 14), and were uniformly negative for cytokeratin, S-100, neuron-specific enolase, and actin. Ultrastructurally, complex interdigitating cell processes were connected by desmosomes. Occasional cytoplasmic filaments were seen. These nodules lack neuroendocrine features, differ from mesothelium, and strongly resemble meningothelial cells. A more accurate term for these lesions is minute meningothelial-like nodules. Their relationship to larger, solitary pulmonary meningiomas is unclear.

So-called “minute pulmonary chemodectoma”.A tumor not related to paragangliomas

Twenty-six cases of so-called "minute pulmonary chemodectoma" are presented. The patient population showed a marked female preponderance, and there appeared to be an association of the lesion with pulmonary injury from a variety of causes including cardiac failure, chronic bronchitis and emphysema, and thromboemboli. Half the cases had multiple tumors. Microscopically, the tumors consisted of nests of cells in the interstitial tissue near small veins. Argentaffin and argyrophil stains failed to demonstrate cytoplasmic granules in any case. By electron microscopy, the nests were composed of large cells with broadly interdigitating processes connected by many well-formed desmosomes. The cytoplasm was filled with numerous 60-A filaments. The Golgi apparatus was prominent, while other organelles were sparse. No secretory granules were identified. It is concluded that the fine structure and lack of silver-positive granules are inconsistent with the morphology of previously reported paragangliomas, but that there is a resemblance at the light and electron microscopic level to meningeal arachnoed cells and the cells of meningiomas.

The fine structure of so-called minute pulmonary chemodectomas

Electron microscopy was performed on several minute tumors of the type called chemodectomas, all from the lung of a single patient. The cells had a whorling pattern with extensive interdigitating cytoplasmic processes joined by desmosomes. Except for tangles of cytoplasmic fibrils, the tumor cells had few distinctive organelles. They had no endocrine-like granules and were not associated with nerves or basement membranes. The tumors had little resemblance to paragangliomas, but displayed a puzzling similarity to meningiomas. Our observations permit no definite conclusions as to the histogenesis of these lung tumors. Viewed in the light of recent physiologic studies, they cast doubt on the presence of special chemoreceptive paraganglia in the lung.

Solitary Primary Chemodectomas of the Lung

Although chemodectomas of microscopic size have been described in lung, larger solitary primary chemodectomas have not been recognized frequently. It is possible that some of the lesions reported as atypical bronchial adenomas may actually represent such tumors. Two instances of probable primary pulmonary chemodectoma are presented.

Minute pulmonary chemodectoma.

The minute chemodectomas of the lung belong to the paraganglioma group of neoplasms, which include carotid and aortic body tumors. They are frequently multiple, small in size, and are nearly always detected fortuitously on histologic examination of sections of a lung taken from an older patient. They are believed to arise from the normal chemoreceptors of the lung. There is no indication that these small neoplasms are functional. It has been proposed that pulmonary chemodectomas may be induced by pulmonary thromboemboli. This possibility gains some support from an analysis of 10 new cases and a review of 46 cases previously reported.

Chemodectoma of the lung.

A case of pulmonary chemodectoma is presented. To date, five lung tumours regarded as chemodectoma have been reported in the literature. An asymptomatic woman, aged 49 years, had in the anterior segment of the right upper lobe a coin lesion, which was treated by segmental resection. Histologically the tumour fulfilled the criteria of chemodectoma.