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Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 8048056, 5 pages https://doi.org/10.1155/2020/8048056 Case Report A Case of Pulmonary Epithelioid Hemangioendothelioma with Literature Review 1 2 1 1 3 Thu Thu Aung, Andrew Chu , Divya Kondapi, Danny Markabawi, Kanish Mirchia, and Pratibha Kaul Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, New York, USA Department of Pulmonary and Critical Care, SUNY Upstate Medical University, Syracuse, New York, USA Department of Pathology, SUNY Upstate Medical University, Syracuse, New York, USA Correspondence should be addressed to Andrew Chu; email@example.com Received 22 March 2020; Revised 31 July 2020; Accepted 16 September 2020; Published 8 October 2020 Academic Editor: Katsuhiro Tanaka Copyright © 2020 Thu Thu Aung et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pulmonary epithelioid hemangioendothelioma is a rare vascular tumor and infrequently described in medical literature as case reports and case series. Diagnosis is often incidental with high index of histopathological suspicion from clinical pathologist. The pathological pattern is quite unique with distinct immunohistochemical stains. Up to this day, there is no established standard treatment owing to the scarcity of this tumor. In this case report, we describe a case of pulmonary epithelioid hemangioendothelioma unexpectedly diagnosed with transthoracic needle biopsy, along with a review of the current literature. 1. Introduction cryoglobulinemia, and polymyalgia rheumatica. She was diagnosed with seronegative Sjögren’s syndrome by her Pulmonary epithelioid hemangioendothelioma (PEH) is a rheumatologist about three years ago and was taking hydro- rare vascular tumor of low-grade malignancy potential. It xychloroquine, mycophenolate mofetil, and prednisone. She was initially termed intravascular bronchioloalveolar tumor was a nonsmoker. Her vital signs on initial evaluation were by Dail and Liebow in 1975 . The term “epithelioid stable. She had no wheezing or crackles on physical examina- hemangioendothelioma” (EHE) was ﬁrst introduced in tion. Pulmonary function tests including spirometry, lung 1982 by Weiss and Ezinger to describe a vascular tumor dis- volumes, and diﬀusion capacity were all within normal range. playing pathological features between hemangioma and Computerized tomography (CT) of the chest revealed scat- angiosacroma . There is no standard of treatment as tered ground glass opacities bilaterally (Figure 1). She under- PEH is extremely rare with only a few case reports and series went bronchoscopy with transbronchial biopsy which published in the medical literature. We report a case of a showed mild peribronchiolar ﬁbrosis with negative infectious middle age female who had multiple pulmonary nodules on (bacterial, viral, and fungal) workup. Her respiratory symp- radiographic imaging and subsequently was diagnosed with toms persisted and she underwent video-assisted thoracot- PEH on transthoracic needle biopsy. A review of literature omy and wedge biopsy of right lower lobe. The biopsy on PEH with emphasis on histopathologic features will be showed benign lung tissue with emphysematous changes discussed in this case report. (airspace enlargement) and focal interstitial and pleural ﬁbrosis. She was managed conservatively. Serial chest CT scans were performed to follow up the pulmonary nodules. 2. Case Report On her latest CT scan of the chest, there was an 8 mm left A 58-year-old lady was referred to our clinic for chest tight- lower lobe pulmonary nodule which appeared to be enlarging ness and shortness of breath. She had a medical history of (Figure 2). She underwent a positron emission tomography subcentimeter pulmonary nodules, peripheral neuropathy, (PET) scan of the whole body which did not reveal any 2 Case Reports in Oncological Medicine the tumor cells. The ﬁndings ﬁt with a low-grade epithelioid hemangioendothelioma (Figures 3, 4, and 5). She was referred to a large oncology center but no treatment was ini- tiated. The shared decision was made to continue surveil- lance of the cancer with yearly PET scan. Since then, she has been followed up over a year with no evidence of cancer progression, symptomatically or radiographically. 3. Discussion Since the ﬁrst pathologic description of EHE by Weiss and Ezinger , there have been over 200 cases of PEH published in the literature. The International Hemangioendothelioma, Epithelioid Hemangioendothelioma and Vascular Disorders (HEARD) Registry has the largest collection of data on this rare disease and its natural history . Very few large studies are summarized by Sardaro et al. . The estimated preva- lence of PEH is less than one in 1 million cases with female predominance, 4 : 1 ratio. Median age of diagnosis is 36 years Figure 1: Our patient’s initial chest CT scan showing scattered old. The liver and lungs are the two most common involved ground glass opacities bilaterally (red circle). organs. Single organ involvement occurred in more than 60% of the patient. The HEARD Registry observed that the most common EHE involvements are in the liver alone (21%), liver plus lung (18%), lung alone (12%), and bone alone (14%). Clinical presentation of PEH varies from being asymp- tomatic to having nonspeciﬁc symptoms. Majority of the patients are asymptomatic on initial presentation. A few patients may present with pleuritic chest pain, hemoptysis, and weight loss. Physical examination is often nonspeciﬁc, decreased breath sounds due to presence of pleural eﬀu- sion, or digital clubbing due to persistent hypoxia . The diagnosis of PEH is often made incidentally by radio- graphic imaging. Radiograpically, PEH can manifest as three distinct imag- ing patterns on chest CT: (1) multiple pulmonary nodules with a perivascular distribution; (2) multiple pulmonary reti- culonodular opacities; or (3) diﬀuse inﬁltrative pleural thick- ening . The major characteristic radiographic feature of PEH is the presence of perivascular nodules which are usu- ally found near medium-sized vessels and bronchi . The nodules can range up to 3 cm in diameter, but most are often Figure 2: Follow-up chest CT scan showing an 8 mm left lower lobe less than 1 cm. Majority of these nodules can be mistaken for pulmonary nodule (red arrow) which appeared to be enlarging. metastatic cancer, but PEH shows little or no progression in size on serial CT scans . There is a trend toward better increased standardized uptake value. She subsequently had prognosis for multinodular pattern of PEH. In the largest transthoracic needle biopsy of the enlarging left lower lobe studies reviewing the relation between radiographic patterns pulmonary nodule. The biopsy revealed an intra-alveolar and prognosis of PEH, multiple pulmonary nodules on CT inﬁltrate of relatively monomorphic tumor cells with scan correspond to have longer survival [5, 9]. However, rounded nuclei and moderate eosinophilic cytoplasm. The pleural involvement with malignant pleural eﬀusion is a poor cells were set in a myxohyaline stroma. Scattered areas prognostic factor [9, 10]. showed intracytoplasmic lumina and intranuclear inclusions. The diagnosis of PEH is made on the basis of histopath- Most of the tumor appeared to be intra-alveolar and the sur- ological features and is conﬁrmed using immunohistochem- ical stain for vascular-endothelial markers. Histology often rounding lung parenchyma showed mildly prominent type II pneumocytes. There was no evidence of signiﬁcant nuclear reveals tumor cells with marked cytologic atypia, centralized atypia, mitoses, or necrosis. Immunohistochemical stains stroma with hyalinization, and central necrosis with varying showed positive staining of the tumor cells for CD31 and calciﬁcation. This central pathology is surrounded by rim of ERG (vascular markers). Pancytokeratin, TTF-1, Pax-8, eosinophilic endothelial cells. More severe atypical cytologic such as larger nuclei, prominent eosinophilic nucleoli, and CAM 5.2, EMA, CDX2, CK20, and CK7 were negative in Case Reports in Oncological Medicine 3 Figure 3: Hematoxylin and eosin stain of transthoracic needle lung biopsy. This slide is at 40x magniﬁcation. The sections show multiple cores of lung parenchyma, some of which contain an intra-alveolar inﬁltrate of relatively monomorphic tumor cells with round nuclei and a moderate eosinophilic cytoplasm. The cells are set in a myxohyaline stroma. Scattered areas show intracytoplasmic lumina, and there are also intranuclear inclusions. Most of the tumor appears to be intra-alveolar and the surrounding lung parenchyma shows mildly prominent type II pneumocytes. There is no evidence of signiﬁcant nuclear atypia, mitoses, or necrosis. Figure 4: Immunohistochemical stain showing uptake of CD31. intranuclear cytoplasmic inclusion can also be seen [11, 12]. tomatic patients. Surgical resection can be performed in Histologic ﬁnding of spindle tumor cells or ﬁbrinous pleuritic the case of a solitary pulmonary nodule or unilateral multi- ple pulmonary nodules with no evidence of metastasis . lesion with tumor cell proliferation are linked to worse prognosis . The deﬁnitive diagnosis is made with immu- Chemotherapy or immunotherapy can be considered in nohistochemical staining of vascular antigens, such as the cases of disseminated or unresectable disease. There CD31, CD34, and factor VIII. Other vascular markers can are several cases of cancer regression or remission achieved be considered for staining are F8, ERG, EMA, and FKBNP12. in patients treated with conventional chemotherapy drugs such as carboplatin, etoposide, and paclitaxel . Since A small case series of PEH showed that CD31 and CD34 are the most expressed markers . PEH is a tumor of vascular origin, antiangiogenetic drugs PEH is an extremely rare entity, and most of the litera- such as thalidomide, lenalidomide, and bevacizumab can ture is composed of case reports and case series. HEARD be considered [15–18]. Several cases have been reported registry has been established with the hope that this will regarding to these antiangiogenetic agents, and some has observed marked response to the treatment . Research lead to more signiﬁcant study of this rare disease and possi- bly to evidence-based guidelines for managing it. However, and trials are needed to further deﬁne the deﬁnite role of for the time being, we do not have such guidelines on the chemo and immunotherapy. management of this rare disease. Treatment throughout In our case, the diagnosis of PEH was an unexpected the literature review has been based on individual basis. ﬁnding on imaging which led to deﬁnitive diagnosis with Spontaneous partial regression of the cancer has been transthoracic needle biopsy. We had high index of suspicion reported in asymptomatic patients . Cancer surveillance for malignancy despite inconclusive transbronchial and with serial CT scans can be a reasonable option in asymp- open-lung biopsies because the nodule was enlarging on the 4 Case Reports in Oncological Medicine Figure 5: Immunohistochemical stain showing uptake of ERG. chest CT. Since our patient was relatively asymptomatic and  A. Sardaro, L. Bardoscia, M. F. Petruzzelli, and M. Portaluri, “Epithelioid hemangioendothelioma: an overview and update no evidence of extrapulmonary manifestation, a shared deci- on a rare vascular tumor,” Oncology Reviews, vol. 8, no. 2, sion was made between the patient, pulmonologist, oncolo- gist, and radiologist to have yearly follow up of this  R. M. S. Amin, K. Hiroshima, T. Kokubo et al., “Risk factors relatively benign cancer. Should there be a progression of and independent predictors of survival in patients with pulmo- cancer in terms of symptomatology or enlarging size on CT nary epithelioid haemangioendothelioma. Review of the litera- scan, consideration will be given regarding chemotherapy ture and a case report,” Respirology, vol. 11, no. 6, pp. 818–825, or immunotherapy as discussed above.  E. Y. Kim, T. S. Kim, J. Han, J. Y. Choi, O. J. Kwon, and J. Kim, 4. Conclusion “Thoracic epithelioid hemangioendothelioma: imaging and pathologic features,” Acta Radiologica, vol. 52, no. 2, In conclusion, we presented a case of a very rare cancer with pp. 161–166, 2011. no known standardized treatment. Although a registry has  H. Baba, M. Tomiyasu, H. Makino, A. Yamamoto, been created, we have very little understanding of PEH. This H. Yokoyama, and Y. Oshiro, “Surgical resection of a primary is largely due to the limited number of cases reported and pulmonary epithelioid hemangioendothelioma in bilateral heterogeneity of the disease process. Further studies are lungs,” General Thoracic and Cardiovascular Surgery, vol. 58, needed to provide answers of this unusual neoplasm. no. 8, pp. 431–433, 2010.  G. T. Noh, K. J. Lee, H. J. Sohn et al., “Pulmonary epithelioid hemangioendothelioma misconceived as pulmonary metasta- Conflicts of Interest sis of other malignancies,” Yeungnam University Journal of Medicine, vol. 33, no. 1, pp. 72–75, 2016. All authors in this article have no conﬂict of interest to disclose.  P. Bagan, M. Hassan, F. L. P. Barthes et al., “Prognostic factors and surgical indications of pulmonary epithelioid heman- gioendothelioma: a review of the literature,” The Annals of References Thoracic Surgery, vol. 82, no. 6, pp. 2010–2013, 2006.  M. Kitaichi, S. Nagai, K. Nishimura et al., “Pulmonary epithe-  D. H. Dail, “Intravascular bronchioloalveolar tumor,” The lioid haemangioendothelioma in 21 patients, including three American Journal of Pathology, vol. 78, pp. 6a-7a, 1975. with partial spontaneous regression,” European Respiratory  S. W. Weiss and F. M. Enzinger, “Epithelioid hemangioen- Journal, vol. 12, no. 1, pp. 89–96, 1998. dothelioma a vascular tumor often mistaken for a carcinoma,”  X. Jinghong and C. Lirong, “Pulmonary epithelioid heman- Cancer, vol. 50, no. 5, pp. 970–981, 1982. gioendothelioma accompanied by bilateral multiple calciﬁed  K. Lau, M. Massad, C. Pollak et al., “Clinical patterns and out- nodules in lung,” Diagnostic Pathology, vol. 6, no. 1, p. 21, come in epithelioid hemangioendothelioma with or without pulmonary involvement: insights from an internet registry in the study of a rare cancer,” Chest, vol. 140, no. 5, pp. 1312–  J. Shao and J. Zhang, “Clinicopathological characteristics of pulmonary epithelioid hemangioendothelioma: a report of 1318, 2011. Case Reports in Oncological Medicine 5 four cases and review of the literature,” Oncology Letters, vol. 8, no. 6, pp. 2517–2522, 2014.  M. Białas, B. Papla, and A. Bulanda, “Immunohistochemical investigation of selected endothelial markers in pulmonary epithelioid haemangioendothelioma,” Polish Journal of Pathol- ogy, vol. 62, no. 4, pp. 236–240, 2011.  B. Ye, W. Li, J. I. A. N. Feng, J.-X. Shi, Y. Chen, and B.-H. Han, “Treatment of pulmonary epithelioid hemangioendothelioma with combination chemotherapy: report of three cases and review of the literature,” Oncology Letters, vol. 5, no. 5, pp. 1491–1496, 2013.  Y. H. Kim, M. Mishima, and A. Miyagawa-Hayashino, “Treat- ment of pulmonary epithelioid hemangioendothelioma with bevacizumab,” Journal of Thoracic Oncology, vol. 5, no. 7, pp. 1107-1108, 2010.  L. Belmont, L. Zemoura, and L. J. Couderc, “Pulmonary Epi- thelioid Haemangioendothelioma and Bevacizumab,” Journal of Thoracic Oncology, vol. 3, no. 5, pp. 557-558, 2008.  R. G. Giancipoli, S. Monti, O. Basturk et al., “Complete meta- bolic response to therapy of hepatic epithelioid hemangioen- dothelioma evaluated with F-ﬂuorodeoxyglucose positron emission tomography/contrast-enhanced computed tomogra- phy: a CARE case report,” Medicine, vol. 97, no. 42, article e12795, 2018.  A. Rosenberg and M. Agulnik, “Epithelioid hemangioendothe- lioma: update on diagnosis and treatment,” Current Treatment Options in Oncology, vol. 19, no. 4, p. 19, 2018.
Case Reports in Oncological Medicine – Hindawi Publishing Corporation
Published: Oct 8, 2020
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