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A.L.H.E. or angiolymphoid hyperplasia with eosinophilia was , for many years, confused with Kimura's disease. Detailed studies performed by pathologists have elucidated the differences between these two diseases. This is a benign condition often presenting with a papules on the head and neck area.


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Angiolymphoid hyperplasia with eosinophilia associated with pregnancy: a case report and review of the literature.

Zarrin-Khameh N, Spoden JE, Tran RM.

Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Arch Pathol Lab Med. 2005 Sep;129(9):1168-71. Abstract quote  

A case of angiolymphoid hyperplasia with eosinophilia (ALH) is reported in a 33-year-old woman who developed an auricular nodule during the second trimester of her pregnancy. Angiolymphoid hyperplasia with eosinophilia usually occurs on the head and neck of young adults and is more common in women than in men.

Characteristic histologic features of ALH present in this case included proliferation of thick-walled blood vessels lined by prominent endothelial cells, infiltration of the interstitium by chronic inflammatory cells (mainly eosinophils), and presence of lymphoid follicles with germinal centers. The auricular tumor was completely excised. Thirteen months after excision, the patient remains tumor free. Although there are not many case reports on ALH during pregnancy or involving use of oral contraceptive pills, sex hormones may play a role in the pathogenesis of ALH.

This hypothesis, in the context of cases previously described in the literature, and the differential diagnosis of ALH are discussed.


Angiolymphoid hyperplasia with eosinophilia.

Endo M, Shibata M, Iwamoto I, Suzuki H, Hayakawa M.

Department of Dermatology, Surugadai Nihon University Hospital, 1-8-13, Kanda-Surugadai, Chiyodaku, Tokyo 101, Japan.

Eur J Dermatol 1998 Apr-May;8(3):175-7 Abstract quote

We report a case of angiolymphoid hyperplasia with eosinophilia (ALHE). Histologically, some vessels were lined with plump endothelial cells. Infiltration by lymphocytes, histiocytes and eosinophils was marked. An arteriovenous malformation and vessels occluded by endothelial cell hyperplasia were present. PCNA staining gave positive results for the nuclei of many of the plump endothelial cells. Electron-microscopic findings disclosed increased metabolic activity in the cells. These observations suggest that the plump endothelial cells, characteristic of ALHE, have high metabolic activity.

These results suggest that blood flow is increased by arteriovenous malformations and that blood pressure is elevated by occlusion, resulting in hyperplasia of plump endothelial cells and accelerated neovascularization.

Angiolymphoid hyperplasia with eosinophilia associated with arteriovenous malformation: a clinicopathological correlation with angiography and serial estimation of serum levels of renin, eosinophil cationic protein and interleukin 5.

Onishi Y, Ohara K.

Department of Dermatology, Toranomon Hospital 2-2-2, Toranomon, Minatoku, Tokyo, 105-0001, Japan.

Br J Dermatol 1999 Jun;140(6):1153-6 Abstract quote

We present a case of angiolymphoid hyperplasia with eosinophilia (ALHE) affecting the auricular area of a 31-year-old man, which clinically mimicked arteriovenous malformation (AVM).

The histology and laboratory data distinctively revealed ALHE, while angiography demonstrated typical findings of AVM. Although several reports have hitherto mentioned the relationship between ALHE and AVM, the aetiology of the disease remains unknown. During the 3 years treatment course, we performed angiography several times to assess the efficacy of the treatments and compared the clinical and pathological findings, based on the hypothesis that AVM might be a cause of ALHE.

This study showed first, that the clinicopathological findings of ALHE correlated with the extent of AVM shown by angiography, so that AVM could be a primary cause of ALHE. Secondly, systemic corticosteroids and local irradiation therapy produced only a temporary effect on the inflammatory changes of ALHE; therefore, surgical resection is recommended as a curative treatment. Thirdly, the patient's serum levels of renin, eosinophil cationic protein and interleukin 5 corresponded closely with the clinical course of ALHE.

Human herpesvirus-8 is not associated with angiolymphoid hyperplasia with eosinophilia.

Bhattacharjee P, Hui P, McNiff J.

Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA.
J Cutan Pathol. 2004 Oct;31(9):612-5. Abstract quote  

Background: Angiolymphoid hyperplasia with eosinophilia (ALHE) is an angioproliferative lesion, typically consisting of single or multiple red papules or nodules in the head and neck region. The etiology of ALHE, whether reactive or neoplastic, is unclear. It has been well documented in the literature that human herpesvirus-8 (HHV-8) DNA is present in the majority of cases of Kaposi's sarcoma; however, there is contradictory data regarding the association of this virus with ALHE.

Methods: We performed immunohistochemical studies for HHV-8 on paraffin-embedded tissue from 23 cases of histologically confirmed ALHE. Polymerase chain reaction (PCR) analysis for HHV-8 DNA was performed on 14 of the 23 cases that had adequate remaining tissue for the procedure. The results of the immunohistochemical studies and PCR analysis were compared.

Results: HHV-8 immunohistochemical studies were negative in all 23 cases of ALHE. PCR-based analysis on 14 cases failed to identify HHV-8 DNA.

Conclusions: Combined data from several, small published studies are equivocal for an association between HHV-8 and ALHE. The results of our large study show no association between HHV-8 and ALHE.

Polymerase chain reaction (PCR) for human herpesvirus 8 and heteroduplex PCR for clonality assessment in angiolymphoid hyperplasia with eosinophilia and Kimura's disease.

Jang KA, Ahn SJ, Choi JH, Sung KJ, Moon KC, Koh JK, Shim YH.

Department of Dermatology, Seoul Paik Hospital, Inje-University, Seoul, Korea.

J Cutan Pathol 2001 Aug;28(7):363-7 Abstract quote

BACKGROUND: Recently, human herpesvirus 8 (HHV-8) has been isolated from almost all cases of Kaposi's sarcoma. It has not been found in most cutaneous hemangioproliferative disorders other than Kaposi's sarcoma. Benign vascular lesions including Kimura's disease were not found to contain the HHV-8 DNA sequence. However, there has been contradictory data concerning the presence of HHV-8 in angiolymphoid hyperplasia with eosinophilia (ALHE). Clonality studies in ALHE and Kimura's disease were rare.

METHODS: We performed polymerase chain reaction (PCR)-based analysis to determine whether HHV-8 is present and heteroduplex analysis of rearranged T-cell receptor (TCR) gene for clonality assessment in paraffin-embedded skin biopsy samples of 7 ALHE and 2 Kimura's disease, taken from immunocompetent patients.

RESULTS: HHV-8 could not be identified in all the cases of ALHE and Kimura's disease. Although 2 cases (2/7) of ALHE and 2 cases (2/2) of Kimura's disease showed positive result for PCR analysis of TCR, all the cases were negative for heteroduplex-PCR.

CONCLUSIONS: We suggest that HHV-8 may not involve in a pathogenetic role in ALHE and Kimura's disease and the failure to demonstrate clonality may be consistent with the reactive nature of these diseases and lack of malignant transformation. In addition, heteroduplex-PCR can be applied to confirm doubtful cases of lymphoma in that heteroduplex-PCR is more specific than PCR as seen in our study.

Cutaneous angiolymphoid hyperplasia with high endothelial venules is characterized by endothelial expression of cutaneous lymphocyte antigen.

Fernandez-Figueras MT, Puig L, Armengol MP, Juan M, Ribera M, Ariza A.

Department of Pathology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

Hum Pathol 2001 Feb;32(2):227-9 Abstract quote

Two cases in which the presence of cutaneous lesions with a characteristic admixture of lymphoid hyperplasia and vascular proliferation lead to the diagnosis of so-called acral pseudolymphomatous angiokeratoma (APA) of children are reported.

Owing to the prominence of its blood vessels, so striking as to be reminiscent of high endothelial venules (HEVs), APA was initially interpreted as a vascular lesion rather than a pseudolymphoma. This resemblance is further compounded by our finding that cutaneous lymphocyte antigen (CLA), an HEV marker, is also expressed in APA epithelioid blood vessels.

Consequently, we believe that "cutaneous angiolymphoid hyperplasia with high endothelial venules" (ALH-HEV), which alludes to the dual nature of proliferating elements and the HEV-like phenotype of the vascular component, would be a better denomination for this entity. Additionally, we speculate that ALH-HEV lymphoid hyperplasia self-perpetuates through the transformation of dermal capillaries into HEVs, which would bind non-skin homing lymphocytes expressing L-selectin and promote their local recruitment and recirculation.


Angiolymphoid hyperplasia with eosinophilia: evidence for a T-cell lymphoproliferative origin.

Kempf W, Haeffner AC, Zepter K, Sander CA, Flaig MJ, Mueller B, Panizzon RG, Hardmeier T, Adams V, Burg G.

Department of Dermatology, University Hospital Zurich, Switzerland.

Hum Pathol 2002 Oct;33(10):1023-9 Abstract quote

Angiolymphoid hyperplasia with eosinophilia (ALHE) is commonly regarded an angioproliferative process characterized by the presence of prominent, bizarrely shaped blood vessels.

These vessels are accompanied by an inflammatory infiltrate that is thought to be a reactive component. Both the cell of origin and the pathogenesis of ALHE remain controversial. To define the histogenesis of this disorder, we analyzed the phenotypic and genotypic profile of the inflammatory infiltrate in ALHE by immunohistochemistry and T-cell receptor gene rearrangement by polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis, as well as automated high-resolution PCR fragment analysis.

Five of 7 ALHE patients displayed a clonal T-cell population and proliferative T-cell activity in lesional tissue. Most of these cases followed a protracted and therapy-reluctant course with recurrences.

These data suggest that ALHE or a subset of ALHE cases harboring a clonal T-cell population may represent a T-cell lymphoproliferative disorder of a benign or low-grade malignant nature.



Angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma) of the breast: report of a case.

Nair M, Aron M, Sharma MC.

Department of Pathology, All India Institute of Medical Sciences, New Delhi.

Surg Today 2000;30(8):747-9 Abstract quote

We report herein the unusual case of a 35-year-old woman found to have angiolymphoid hyperplasia with eosinophilia (ALHE) of the breast.

The patient was initially referred to our hospital for investigation of a well-circumscribed breast lump, 2.5 cm in diameter, and a clinical diagnosis of fibroadenoma was made. However, fine-needle aspiration cytology of the lump revealed an admixture of lymphocytes and eosinophils. Therefore, the lump was excised and microscopic examination showed features of ALHE. No evidence of recurrence of the lump has been seen in the 2 years since this excision.

To the best of our knowledge, this is the first case to be documented of ALHE arising in the breast.


Angiolymphoid hyperplasia with eosinophilia in the colon: a novel cause of rectal bleeding.

Berney DM, Griffiths MP, Brown CL.

Department of Histopathology and Morbid Anatomy, Medical and Dental School of St Bartholomew's, London, UK

J Clin Pathol 1997 Jul;50(7):611-3 Abstract quote

Angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) is an uncommon but distinctive lesion seen principally in the skin. A case of severe gastrointestinal haemorrhage in a 63 year old male is reported, which necessitated a right hemicolectomy. A lobulated nodule was seen macroscopically that had the histological appearance of angiolymphoid hyperplasia with eosinophilia, with sheets of lymphocytes and eosinophils associated with many vessels showing plump and pleomorphic endothelial cells.

This is the first reported case of this entity in the large intestine.

Angiolymphoid Hyperplasia With Eosinophilia (Epithelioid Hemangioma) of the Lung
A Clinicopathologic and Immunohistochemical Study of Two Cases

Cesar A. Moran, MD and Saul Suster, MD
Am J Clin Pathol 2005;123:762-765 Abstract quote

Two cases of primary angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma) (ALHE/EH) of the lung are described. Both patients are white, a 60-year-old man and a 27-year-old woman. One patient had a long-standing history of asthma, and the other had symptomatology related to the pulmonary mass.

Wedge resections were performed in both cases, and both lesions shared similar histopathologic changes, mainly the presence of a tumor mass with a marked presence of eosinophils in the background, lymphoid hyperplasia, and marked proliferations of small-caliber vessels. Immunohistochemical studies using leukocyte common antigen, L-26, and UCHL-1 nicely stained the lymphoid component of the lesion, and CD31 clearly outlined the vascular component of the process. Clinical follow-up demonstrated that the woman died of status asthmaticus, and the man was alive and well 1 year after surgical resection of the lesion.

Both cases highlight the ubiquitous distribution of ALHE/EH and underscore the importance of keeping these lesions in the differential diagnosis of vascular and lymphoid lesions of the lung.

Angiolymphoid hyperplasia with eosinophilia affecting the oral mucosa: report of a case and a review of the literature.

Bartralot R, Garcia-Patos V, Hueto J, Huguet P, Raspall G, Castells A.

Department of Dermatology, Hospital General Universitari Vall d'Hebron, Barcelona, Spain.

Br J Dermatol 1996 Apr;134(4):744-8 Abstract quote

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon disorder of unknown aetiology. Clinically, it is characterized by cutaneous papules or nodules on the head and neck, and extracutaneous involvement is rare.

We report a 30-year-old woman who had an asymptomatic submucosal nodule on the upper lip, which histopathologically showed features of ALHE, and review the previously described 15 cases of oral ALHE.


Unilateral angiolymphoid hyperplasia with eosinophilia involving the left arm and hand.

Arnold M, Geilen CC, Coupland SE, Krengel S, Dippel E, Sproder J, Goerdt S, Orfanos CE.

Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Germany.

J Cutan Pathol 1999 Oct;26(9):436-40 Abstract quote

A case report of recurrent angiolymphoid hyperplasia with eosinophilia (ALHE) in an otherwise healthy 20-year-old female with manifestation of the disease limited to the left arm and hand is presented together with brief evaluation of the literature as well as the features distinguishing ALHE and Kimura's disease. Immunohistochemical investigations support the hypothesis that ALHE represents a reactive inflammatory lesion rather than a benign vascular neoplasm. A viral cause of ALHE (e.g., HHV8 or Epstein-Barr virus (EBV)) could not be demonstrated.

The recurrent nature of the disease is shown by this case, which also demonstrates the need for frequent medical and surgical management.


Angiolymphoid hyperplasia with eosinophilia: report of a lesion mimicking soft tissue tumor of extremely long duration.

Toth E, Orosz Z, Rahoty P.

Department of Surgery, National Institute of Oncology, Budapest, Hungary.

Pathol Res Pract 2000;196(2):99-101 Abstract quote

We present a large sized lesion of the right upper arm in which characteristics of the angiolymphoid hyperplasia with eosinophilia (ALHE) intermingled with those of Kimura's disease (KD).

The laboratory findings, the prominent vascular proliferation and the features of endothelial cells were suggestive of ALHE. However, the long duration of the disease, the site of involvement, the abundant lymphoid component forming lymph follicles with germinal centers and the fibrosis are features of KD.

In agreement with other reports, our case shows that clinicopathologically there is an overlap between ALHE and KD.


Angiolymphoid Hyperplasia With Eosinophilia Showing Prominent Granulomatous and Fibrotic Reaction: A Morphological and Immunohistochemical Study.

From the *CIPAX-Surgical Pathology and Cytopathology Institute, Sao Jose dos Campos, Sao Paulo State-Brazil; and daggerDepartment of Pathology, Catholic University of Chile, School of Medicine, Santiago-Chile.

Am J Dermatopathol. 2006 Dec;28(6):514-517. Abstract quote

Angiolymphoid hyperplasia with eosinophilia is an uncommon condition that usually presents in early to middle-aged adults as multiple red nodules or plaques, most commonly on the head and neck. It can also occur on the trunk and limbs, and rarely at other sites such as the breast and oral mucosa. Although one-third of these lesions recur, surgical excision is curative.

The histopathological hallmark is the presence of blood vessels with plump epithelioid endothelial cells. The nonvascular component consists of histiocytes, plasma cells, eosinophils, and lymphocytes. The occurrence of numerous giant cells in the stroma of angiolymphoid hyperplasia with eosinophilia is extremely unusual and such a finding in association with diffuse granulomatous/fibrous reaction has not been reported.

We describe such a lesion that developed in the wrist of a 34-year-old pregnant female.
Intra-arterial angiolymphoid hyperplasia with eosinophilia.

Departement de Pathologie, Hopital Henri Mondor, Universite Paris 12 Val de Marne, Creteil, France.


J Cutan Pathol. 2008 May;35(5):495-8. Abstract quote

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare skin disorder of unknown etiology. This paper describes the case of a 34-year-old man with a lesion located on the right part of his forehead.

Microscopically, it displayed a typical morphology of ALHE. However, it was exceptional by its intra-arterial location and its prominent lymphocytic rim-like component.

Differential diagnoses, with special emphasis to organized thrombosis and juvenile arteritis, are discussed here.

Angiolymphoid hyperplasia with eosinophilia showing characteristics of Kimura's disease.

Chung TS, Kim DK, Yoon MS, Yang WI.

Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea.

J Dermatol 2000 Jan;27(1):27-30 Abstract quote

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign condition affecting principally the head and neck region of young females.

We describe a 42-year-old female patient of ALHE showing the typical changes of endothelial cells and features similar to Kimura's disease in histologic and immunohistochemical findings.


Angiolymphoid hyperplasia with eosinophilia masquerading as Kimura disease.

Ramchandani PL, Sabesan T, Hussein K.

Maxillofacial Unit, Poole Hospital, Longfleet Road, Poole, Dorset BH15 2JB, UK.
Br J Oral Maxillofac Surg. 2005 Jun;43(3):249-52. Abstract quote  

Angiolymphoid hyperplasia with eosinophilia is a rare benign vasoproliferative disease of unknown cause, which can present as tumour-like nodules in the head and neck.

We treated a patient who showed some of the features of Kimura disease (KD), which is an important differential diagnosis, because of the latter's association with renal disease.

Involvement of regional lymph nodes and distinction from angiolymphoid hyperplasia with eosinophilia.

Kuo TT, Shih LY, Chan HL.

Chang Gung Medical College, Department of Pathology, Taipei, Taiwan, Republic of China.

Am J Surg Pathol 1988 Nov;12(11):843-54 Abstract quote

The clinicopathologic features of nine patients with Kimura's disease and 15 patients with angiolymphoid hyperplasia with eosinophilia (ALHE) were studied and compared in order to clarify the confusion between these two entities.

The common features shared by both conditions included male predominance, predilection for the head and neck regions, tendency to recur, and vascular nature of the lesion with lymphoid and eosinophilic infiltrates. However, Kimura's disease was usually seen in younger individuals for a longer duration and occurred as a deeply seated, large soft-tissue mass, without significant change of the overlying skin initially. In addition, it was often accompanied by peripheral blood eosinophilia and elevated serum IgE. In contrast, ALHE lesions were multiple small dermal papular or nodular eruptions observed in older patients and present for a shorter duration; they were less frequently accompanied by peripheral blood eosinophilia.

The main histopathological difference was the presence of "histiocytoid" or "epithelioid" blood vessels in ALHE but not in Kimura's disease. Kimura's disease was further characterized by eosinophilic folliculolysis; IgE deposits in the germinal centers; and frequent involvement of regional lymph nodes, salivary glands, and skeletal muscles. The eosinophilic infiltration, especially the formation of eosinophilic microabscesses, along with increased number of small blood vessels, perinodal eosinophilic infiltration, and eosinophilic folliculolysis characterized the nodal involvement by Kimura's disease.

Our study indicates that Kimura's disease and ALHE are two distinct clinicopathologic entities. We place particular emphasis on the involvement of regional lymph nodes in Kimura's disease. In addition, we observed Charcot-Leyden crystals and polykaryocytes in both conditions. One of the patients with Kimura's disease also had an associated nephrotic syndrome.



Angiolymphoid hyperplasia with eosinophilia successfully treated with a long-pulsed tunable dye laser.

Rohrer TE, Allan AE.

Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA.

Dermatol Surg 2000 Mar;26(3):211-4 Abstract quote

BACKGROUND: To date, both surgical excision and laser treatments for angiolymphoid hyperplasia with eosinophilia (ALHE) have resulted in scarring.

OBJECTIVE: Based on the principle of selective photothermolysis, we considered employing the newer long-pulsed tunable dye laser in the treatment of ALHE, as less scarring would be expected and deeper blood vessels could be ablated.

METHODS: After punch biopsy specimens confirmed the diagnosis, the patient was treated on two separate occasions, 2 months apart with a long-pulsed tunable dye laser.

RESULTS: The lesions flattened after the initial treatment and resolved after a second treatment. No scarring was detectable and no recurrence was noted in follow-up after 1 year.

CONCLUSION: We conclude that the long-pulsed tunable dye laser can be employed successfully to treat superficial lesions of ALHE, particularly in cosmetically sensitive areas.

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