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Eruptive Cherry Hemangiomatosis Associated with Multicentric Castleman Disease a Case Report and Diagnostic Clue

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Eruptive Cherry Hemangiomatosis Associated with Multicentric Castleman Disease a Case Report and Diagnostic Clue OBSERVATION Eruptive Cherry Hemangiomatosis Associated With Multicentric Castleman Disease A Case Report and Diagnostic Clue David C. Fajgenbaum, MSc; Misha Rosenbach, MD; Frits van Rhee, MD, PhD; Adnan Nasir, MD; Jason Reutter, MD Background: Eruptive cherry hemangiomatosis, which the cutaneous proliferations improved in association involves the sudden onset of multiple small vascular pro- with the systemic disease. liferations, has been rarely reported as a heralding sign of multicentric Castleman disease (MCD) and other lym- Conclusions: There is a scarcity of literature describ- phoproliferative diseases. We report a case wherein the ing the association between eruptive cherry hemangio- rapid appearance of cherry hemangiomata is the present- matosis and MCD. The likely underlying mechanism is ing sign of MCD. hypersecretion of vascular endothelial growth factor sec- ondary to an elevated interleukin 6 level. Failure to rec- ognize this association may have led to diagnostic de- Observations: A 25-year-old man with a 10-year his- lays. The authors suggest careful evaluation and follow-up tory of benign vascular growths developed 23 cutane- of all patients presenting with the sudden onset of cherry ous vascular proliferations and systemic symptoms 5 hemangiomata, particularly with systemic symptoms, days prior to presentation. Biopsy of the cutaneous lymphadenopathy, or other benign vascular endothelial lesions revealed a polypoidal proliferation of vessels growths, for the potential development of MCD and other consistent with cherry hemangiomata. Laboratory lymphoproliferative diseases. studies disclosed systemic abnormalities, and the find- ings of a subsequent lymph node biopsy confirmed MCD. Combination chemotherapy was initiated, and JAMA Dermatol. 2013;149(2):204-208 HYSICIANS HAVE REPORTED (ECH) in the setting of systemic symp- cases of eruptive cutaneous toms should be fully evaluated for the po- lesions as manifestations of tential development of MCD and other lym- underlying hemato-onco- phoproliferative diseases. logic diseases for more than a century.1-6 Eruptions of cherry heman- P REPORT OF A CASE giomata, glomeruloid hemangiomata, pyo- genic granulomas, hypertrichosis lanugi- nosa, vellous hair cysts, steatocystomas, A 25-year-old man first presented in 2010 seborrheic keratoses, acquired ichthyo- with a 2-month history of inguinal lymph- sis, and keratoacanthoma have been as- adenopathy and 4.5-kg (10-lb) weight loss; sociated with hematologic abnormalities a 5-day history of fatigue, right upper quad- and malignancies, including multiple my- rant abdominal pain, “sudden appearance eloma, Hodgkin lymphoma, and POEMS of blood moles,” night sweats, and an- (polyneuropathy, organomegaly, endo- orexia; and 2-day history of fevers and pleu- Author Affiliations: Perelman crinopathy, myeloma, and skin changes) ritic chest pain. Physical examination Author Aff School of Medicine School of M (Mr Fajgenbaum) and syndrome. disclosed 23 noncompressible, 0.1- to 0.5- (Mr Fajgen Department of Dermatology We report a case of multicentric Castle- cm, nontender, smooth, dome-shaped, Departmen (Dr Rosenbach), University of man disease (MCD) presenting with mul- bright-red vascular-appearing lesions over Rosenbach) Pennsylvania, Philadelphia; tiple cherry hemangiomata and profound the trunk and upper limbs (Figure 1). Two Pennsylvan Multiple Myeloma Institute, systemic symptoms during a 5-day period. of the lesions had an erythematous base. Multiple M University of Arkansas for This case represents an important associa- The clinical examination was compared University Medical Sciences, Little Rock Medical Sci (Dr van Rhee). Dr Nasir is in tion that has been infrequently reported in with a patient-supplied photograph that (Dr van Rh private practice in Raleigh and the literature. We propose a possible mecha- confirmed patient and family member re- private prac Dr Reutter is in private practice nism and suggest that patients presenting ports that the lesions were new and sud- Dr Reutter in Greensboro, North Carolina. with eruptive cherry hemangiomatosis den in onset. in Greensbo JAMA DERMATOL/ VOL 149 (NO. 2), FEB 2013 WWW.JAMADERM.COM 204 ©2013 American Medical Association. All rights reserved. Corrected on February 27, 2014 Downloaded From: https://jamanetwork.com/ on 09/27/2021 A Figure 2. Angiolipoma biopsy specimen showing atypical vascular proliferations within lipomatous tissue (hematoxylin-eosin, original magnification ×40). B Figure 3. Skin biopsy specimen showing lobular proliferation of vessels with no atypia or abnormal infiltrates (hematoxylin-eosin, original magnification ×2). inguinal lymphadenopathy in 2005 and 2010. A 2.5-cm sig- moid tubular colonic adenoma, noted as “highly vascular- ized” by pathological report, caused significant lower gas- trointestinal tract bleeding in 2009. One month prior to presentation, seven 1- to 2-cm subcutaneous masses, his- topathologically consistent with angiolipomas, were noted Figure 1. Eruptive vascuar proliferations noted on the patient’s trunk and on the patient’s abdomen and flank (Figure 2). extremities. A, A 25-year-old man with cutaneous vascular eruptions on the Computed tomograms of the chest and abdomen trunk and upper extremities. B, A close-up view of a lesion at the showed ascites, pleural effusions, mediastinal and hilar suprasternal notch. lymphadenopathy, and splenomegaly. These findings were interpreted as a lymphoproliferative disorder or other he- Laboratory studies revealed a mildly elevated alkaline matologic malignancy. However, the fulminant clinical phosphatase level and mild thrombocytopenia. An abdomi- presentation was thought to be more consistent with a nal ultrasonogram showed a hyperechogenic lesion in the viral syndrome, and the radiologic abnormalities were con- liver interpreted as a benign hemangioma. sidered reactive. The cutaneous eruptions were dis- Medical history was pertinent for several benign vas- missed as being unassociated, and the patient was dis- cular growths beginning up to 10 years before presenta- charged with a presumed viral illness. tion. In 2000, a varicocele was discovered, repaired surgi- The patient returned the next day for a prolonged, cally, and then revised after a bypass vessel grew around 7-week hospitalization notable for multisystem organ fail- the surgical occlusion. During a 2002 ophthalmic exami- ure, continued growth of his cutaneous vascular prolif- nation, an ophthalmologist noted highly vascularized reti- erations, left eye blindness caused by an acute retinal hem- nas. Two separate dermatologists incidentally noted mild orrhage, hypoalbuminemia, anasarca, acute transaminitis, JAMA DERMATOL/ VOL 149 (NO. 2), FEB 2013 WWW.JAMADERM.COM 205 ©2013 American Medical Association. All rights reserved. Corrected on February 27, 2014 Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table. Multicentric Castleman Disease and Eruptive Cherry Hemangiomatosis Markers Peak Levels Size of Eruptive Cherry Total No. of New Eruptive Variable Hemangiomata (Mean), cm Cherry Hemangiomata CRP, mg/L IL-6, pg/mL VEGF, pg/mL Hospitalization for exacerbation 0.1-0.5 (0.3) 23 360 6 NM 1 Remission 1 0.1-0.2 (0.15) 5 NM NM NM Hospitalization for exacerbation 0.2-0.7 (0.55) 3 NM 9 NM 2 Remission 2 0.1-0.5 (0.3) 0 10 6 348 Hospitalization for exacerbation 0.5-1.0 (0.75) 2 247 11.2 354 3 Remission 3 0.1-0.2 (0.15) 0 Ͻ0.5 7317a 48 Abbreviations: CRP, C-reactive protein; IL-6, interleukin 6; NM, not measured; VEGF, vascular endothelial growth factor. SI conversion factor: To convert C-reactive protein from milligrams per liter to nanomoles per liter, multiply by 9.524. a Following administration of siltuximab, interleukin 6 levels are no longer accurate or reliable, because the test measures levels of interleukin 6 complexed to the monoclonal antibody. Blood supply to proliferative lymph nodes IL-6 VEGF MCD lymphocyte Proliferative B-lymphocytes Capillary Increased angiogenesis ECH IL-6 Figure 4. Mechanism of multicentric Castleman disease (MCD) to eruptive cherry hemangiomatosis (ECH). IL-6 indicates interleukin 6; VEGF, vascular endothelial growth factor. anemia, and thrombocytopenia. Extensive infectious dis- (to convert to nanomoles per liter, multiply by 9.524), ease, rheumatologic, hematologic, and oncologic evalu- vascular endothelial growth factor (VEGF) level of ations, excluding a lymph node biopsy, did not yield a 354 pg/mL (reference range, 9-86 pg/mL), interleukin diagnosis. High-dose methylprednisolone, adminis- 6 (IL-6) level of 12.3 pg/mL (reference range, 0-6 tered empirically, brought about clinical improvement pg/mL), and interleukin 8 level of 241 pg/mL (refer- after 3 weeks. He was discharged without a diagnosis, and ence range, 0-5). Additional pertinent laboratory stud- the vascular proliferations had decreased in size and faded ies included normal immunoglobulin levels, negative in color. urine protein electrophoresis, negative serum protein Two weeks after discharge, the patient presented with electrophoresis, negative light chain restriction, nega- 5 new vascular proliferations, growth of the previous le- tive fluorescent in situ hybridization/cytogenetics, sions, and increasing inguinal lymphadenopathy. With negative cryoglobulins, and negative HHV-8 quantita- hematoxylin-eosin staining, shave biopsy specimens re- tive polymerase chain reaction. Hemangiomata diam- vealed a polypoidal lobular proliferation of thin-walled eter peaked at 0.5 to 1.0 cm. He was treated with a vessels with no atypia, no
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