Hemangioendothelioma

To the Editor:

We read with great interest the article by Cronin et al (1) in CHEST (February 2004) entitled "Pulmonary Epitheloid Hemangioendothelioma: An Unusual Case and Review of the Literature." In their article, the authors commented on several aspects of pulmonary epithelioid hemangioendothelioma, including the rarity of epithelioid hemangioendothelioma (EHE) to the lung, the ability to make this diagnosis by transbronchial biopsy, the fact that EHE can affect various organs, the varied prognosis for patients with EHE, the varied response with chemotherapy, and, notably, the fact that some patients have shown full regression of EHE without any treatment. We agree with the authors that the rarity of this condition, the lack of clear standards for treatment, and the partial-to-complete spontaneous regression of EHE seen in some patients up to 15 years from initial detection makes it difficult to decide on the most appropriate treatment. (2) However, we do not necessarily think that the involvement of other organs such as the liver translates into poor survival, as commented on by the authors. Long-term follow-up of [greater than or equal to] 20 years has been reported in many cases of EHE involving both the lung and liver, with a survival time of up to 27 years reported.

Partial hepatectomy and liver transplantation for diffuse involvement is now a standard treatment for localized and diffuse involvement of the liver with EHE. Marino et al (3) reported a 76% 5-year survival rate for 10 patients with EHE involving the liver who underwent liver transplantation. Five patients who received transplants were free of metastatic disease, although two patients died at 3 months and 16 months. Surprisingly, four of those patients who had undergone transplantation had microscopic metastasis to the hilar lymph nodes, chest wall, lung, pleura, or diaphragm. All patients with metastasis were alive at the time of reporting after a mean ([+ or -] SD) duration of 40.6 [+ or -] 22 months. The authors concluded that liver transplantation was a reasonable procedure for bulky, otherwise unresectable EHE even in the presence of metastatic disease.

The treatment for localized lung lesions involves local resection, whereas diffuse lung lesions have historically been treated with chemotherapy in many instances. Reports on the use of intraarterial 5-fluorouracil, doxorubicin, and newer agents like interferon-[[alpha].sub.2]b and interleukin-2 for chemotherapy have provided mixed results. High-dose chemotherapy with autologous stem-cell rescue also has been used with mixed results. (4) Radiotherapy is widely considered to be ineffective and has been used to palliate pain from bone involvement. Progesterone and estrogen receptors have been expressed on tumor cells, and we think that there may be a role for hormonal therapy in patients with diffuse pulmonary disease.

Due to the inconsistent therapeutic results with surgery, the lack of proven effective chemotherapy, and the possibility of regression in some patients with multiorgan involvement from EHE, treatments should still be individualized. Multisystemic involvement should not equate necessarily to a poor prognosis. Hormonal therapy should be studied closely to see whether there is any beneficial effect on progesterone and estrogen receptor-positive tumor cells. Due to the rarity of this disease, double-blind randomized controlled studies investigating at various management strategies will not be possible. Clinical registries such as the Armed Forces Institute of Pathology Registry and the International Hemangioendothelioma, Epithelioid Hemangioendothelioma and Vascular Disorders Registry are places where physicians as well as patients and their families can share their symptoms and treatments, along with response rates and relapses. Such registries may help both patients and physicians alike in following the natural history of the disease and its response to different therapeutic regimens.

Jacques Kpodonu, MD

Cimenga Tshibaka, MD

Malek G. Massad, MD, FCCP

The University of Illinois at Chicago

Chicago, IL

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml).

Correspondence to: Malek G. Massad, MD, FCCP, University of Illinois at Chicago, 840 S Wood St, CSB Suite 417 (MC 958), Chicago, IL 60612; e-mail: mmassad@uic.edu

REFERENCES

(1) Cronin P, Arenberg D. Pulmonary epithelioid hemangioendothelioma: an unusual case and review of the literature. Chest 2004; 125:789-792

(2) Weiss SW, Ishak KG, Dail DH, et al. Epithelioid hemangioendothelioma and related lesions. Semin Diagn Pathol 1986; 3:259-287

(3) Marino IR, Todo S, Tzakis AG, et al. Treatment of hepatic epithelioid hemangioendothelioma with liver transplantation. Cancer 1988; 62:2079-2084

(4) Kadrin RL, Mark EJ. Weekly clinicopathological exercises: case 6-2000: hemoptysis in a 20 year old man with multiple pulmonary nodules. N Engl J Med 2000; 342:572-575

To the Editor:

Kpodonu and others have written regarding our report in CHEST (February 2004) (1) of a patient with epithelioid hemangioendothelioma of the lung, and they have cited additional information about this very rare condition. They have correctly pointed out the range of prognoses that are associated with patients who receive this diagnosis and added liver transplantation to the possible list of treatments that one might consider in cases of extensive hepatic involvement. We thank them for bringing this to our attention and acknowledge the reports cited in their correspondence. (2-4) We agree that it is impossible to point to any accurate standard of care for such a rare condition, especially one with a natural history that appears to be so variable from patient to patient. Kpodunu and colleagues advocated for the use of registries to assist patients and clinicians in decision making about this and other rare conditions, in which randomized trials are not feasible, an idea that we support enthusiastically.

Douglas Arenberg, MD

Paul Cronin, MBBCh

University of Michigan

Ann Arbor, MI

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml).

Correspondence to: Douglas Arenberg, MD, 1150 W Medical Center Dr, 6301 MSRB III, Box 0642, Ann Arbor, MI 48109; e-mail: umich.edu

REFERENCES

(1) Cronin P, Arenberg D. Pulmonary epithelioid hemangioendothelioma: an unusual case and a review of the literature. Chest 2004; 125:789-793

(2) Kradin RL, Mark EJ. Case 6-2000: hemoptysis in a 20-year-old man with multiple pulmonary nodules. N Engl J Med 2000; 342:572-578

(3) Marino IR, Todo S, Tzakis AG, et al. Treatment of hepatic epithelioid hemangioendothelioma with liver transplantation. Cancer 1988; 62:2079-2084

(4) Madariaga JR, Marino IR, Karavias DD, et al. Long-term results after liver transplantation for primary hepatic epithelioid hemangioendothelioma. Ann Surg Oncol 1995; 2:483-487

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