An Overlap of Angiolymphoid Hyperplasia with Eosinophilia and Kimura's Disease: Successful Treatment of Skin Lesions with Cryotherapy.

Kimura's disease is characterized by a triad of painless subcutaneous masses, eosinophilia in the peripheral blood and in tissues with marked increase in Serum Ig E. Angiolymphoid hyperplasia with eosinophilia (ALHE) manifests with the presence of dermal papules and nodules. Unique clinical, histopathological, and biochemical findings are noted in these individual entities. A 32-year-female presented with multiple nodules in the axillae for 2 years. Peripheral smear showed eosinophilia with AEC of 6080. Histopathological examination showed features of overlap. Antinuclear antibody immunoflorescence was was negative. CD31, CD34, and FVIII were positive in vascular component. A CT chest revealed left axillary lymphadenopathy. The patient was treated with Cryotherapy and there was complete regression of skin lesions, with no recurrence after 1 year of follow-up. ALHE and KD are common in the head and neck region, but no reports of an overlap, presenting with lesions in the axillae are available to date, to the best of our knowledge. Response of skin lesions to cryotherapy is highlighted.

What was known?

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign vascular tumor. Kimura's disease is characterized by a triad of subcutaneous masses in the head and neck region, peripheral eosinophilia, and elevated serum immunoglobulin E (IgE) levels. Earlier, Kimura's disease was considered as a variant of ALHE, but now is considered to be a separate entity. The most common site of involvement is the head and neck region for both the entities. Histopathology of Kimura's disease shows follicular hyperplasia with reactive germinal centers, and in ALHE, there are vascular channels with florid intimal proliferation and epithelioid endothelial cells with CD31, CD34, and F VIII positivity on immunohistochemistry. Systemic complications are common in Kimura's disease.

Introduction

Kimura's disease was first described in 1937 by Kim and Szeto in the Chinese literature and later by Kimura et al. in 1948. Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare vasoproliferative disease with a benign nature. The condition was first described by Wells and Whimster in 1969. Both Kimura's disease and angiolymphoid hyperplasia are of unknown etiology. The most common site of involvement for both the entities is head and neck. Kimura's disease is usually associated with systemic complications.

Case Report

A 32-year-old female presented with a history of multiple itchy nodules in the axillae for 2 years. The history of bleeding from the lesions was elicited. There was a history of recurrence of lesions after trichloroacetic acid applications (100%) and radiofrequency ablations on various occasions (done outside our institution, treated with a provisional diagnosis of pyogenic granuloma). The patient had recurrent episodes of Raynaud's phenomenon. On examination, there were multiple, nontender, hyperpigmented papules and nodules in the left axilla and supraclavicular area [Figure 1]. A differential diagnosis of pyogenic granuloma, eccrine poroma, lymphocytoma cutis, cutaneous secondaries, and apocrine tumors were considered. Laboratory data revealed eosinophils of 35% with eosinophilia in peripheral smear. Absolute eosinophil count (AEC) was 6080. The results of renal function tests, liver function tests, and urine routine were within the normal limits. The chest radiograph was unremarkable. ANA was negative (1:100 dilution). Excision biopsy of the lesion with HPE showed epidermis with stratified squamous epithelium. Dermis showed groups of lymphoid follicles with prominent germinal center [Figure 2] with numerous proliferating blood vessels lined by plump epithelioid endothelial cells with a “hob-nail” or “cobblestone” appearance [Figure 3] and the intervening tissue shows a mixture of eosinophils and lymphocytes [Figure 4]. Stains and cultures were negative for bacteria, fungi, and mycobacteria. Immunohistochemistry with special markers for CD 31 [Figure 5a], CD 34 [Figure 5b], and FVIII was positive only in vascular components. Serum Ig E was more than 3000 i.u./mL (Normal <158 i.u./mL). A chest CT scan revealed left axillary lymphadenopathy, the largest measuring 15 × 23 mm [Figure 6]. Finally, a diagnosis of an overlap of AHLE and Kimura's disease was made. Raynaud's phenomenonwas treated with inj. enoxaparin 20 mg s/c, tab. aspirin 150 mg, tab cilostazol 100 mg 6 BD.

Figure 1

Hyperpigmented papules and nodules in left axillae

Figure 2

Dermis showing groups of lymphoid follicles with germinal centers H and E, ×45

Figure 3

Numerous vascular channels lined by plump endothelial cells (arrow marks) (H and E, ×200)

Figure 4

Intervening tissue showing eosinophils (red cells) and lymphocytes H and E ×45

Figure 5

(a and b) CD 31 and CD34 positive in vascular channels (H and E, ×45)

Figure 6

CT chest revealing left axillary lymphadenopathy

Skin lesions were treated with cryotherapy. Two to three freeze–thaw cycles with 10-s freezing and 2-min thawing per session were done at weekly intervals for 2 weeks. There was complete regression of skin lesions [Figures 7 and 8] with no recurrence after 1 year of follow-up. There were no episodes of Raynaud's phenomenon after 1 year of follow-up.

Figure 7

Complete regression of lesions following cryotherapy

Figure 8

Complete regression of lesions following cryotherapy

Discussion

Kimura's disease, first described in China in 1937 by Kim and Szeto[12] in 1937, is characterized by a triad of subcutaneous masses in the head and neck region, peripheral eosinophilia, and elevated serum immunoglobulin E (IgE) levels.[2] ALHE was originally described by Wells and Whimster in 1969[3] is an entity which presents with proliferative vascular lesion of skin and mucous membraneswhich is benign in nature, with a chronic course. In the past, Kimura's disease was classified as a variant of ALHE, but today it is considered as a different entity.[1] The unique features of Kimura's disease and angiolymphoid hyperplasia with eosinophilia are summarized in Table 1.

Table 1

Kimura's disease versus ALHE

The patient presented in this study had the classic triad of Kimura's disease. Clinically, the presence of multiple papules and nodules with a history of occasional bleeding from the lesions simulates lesions of ALHE, but the presence of lymphadenopathy suggests a pointer toward Kimura's disease. Histologically, there was keratinized squamous epithelium with underlying groups of lymphoid follicles with well-formed germinal centers, which is a feature of Kimura's disease, intervening tissue showed a mixture of eosinophils and lymphocytes. However, the presence of vascular channels with plump endothelial cells with a “hob-nail pattern” or “cobblestone appearance”[7] is a distinctive feature of angiolymphoid hyperplasia and eosinophilia. Immunohistochemistry with positive CD31, CD34, and FVIII were seen in vascular channels. The coexistence of these two entities in the same patient has been described earlier,[89] although the pathogenesis, clinical, and histopathological features of both appear separate. This patient also had repeated episodes of Raynaud's phenomenon, which is a finding more commonly reported in Kimura's disease.

The treatment of Kimura's disease is problematic. Localized lesions can be treated with surgical excision. Systemic agents such as corticosteroids,[4] cytotoxic agents, and cyclosporine are tried. In ALHE, surgical excision is the preferred treatment. Other options tried are cryotherapy,[10] laser therapy (CO2 laser, argon laser, and 585-nm-pulsed-dye laser), intralesional therapy with (bleomycin, vinblastine, and fluorouracil) have been tried. Our patient had already had multiple lesions excised, but invariably with recurrence. Cryotherapy was therefore tried in our patient. Cryotherapy causes necrosis of vascular lesions, which elicits an inflammatory response, and clearance of lesions.[11] There was no recurrence of skin lesions after 1 year of follow-up. In view of Raynaud's phenomenon, the patient was started on tab aspirin 150 mg, inj. enoxaparin 20 mg s.c., and tab. cilostozol 100 mg B.D. The patient had no recurrence of Raynaud's phenomenon on 1 year of follow-up.

Conclusion

There is a concept that ALHE and Kimura's disease are two entities of the same spectrum, specific differences are observed. We here-in report a case of an overlap, with features of Kimura's disease and ALHE. Cryotherapy followed. No reports of an overlap, presenting with lesions in the axillae are available to date, to the best of our knowledge.

What is new?

Angiolymphoid hyperplasia and Kimura's disease had been considered as separate entities. However, there are a few reports showing an overlap of these entities. Herein, we present a case of a female patient who had features of clinical, serological, and histopathological overlap of both the entities. The patient also had lesions in the axillae, with overlap features and a successful treatment of skin lesions with cryotherapy, for the skin lesions, with no relapse at 1 year of follow-up, which is not reported before.