Angiolymphoid hyperplasia with eosinophilia of the scalp. (A case report).
Angiolymphoid hyperplasia with eosinophilia is a rare and distinct clinicopathologic entity. Kimura, in 1948, described lesions characterised by eosinophilic lymphofolliculosis of the skin with vascular proliferation. Hence, the disease was named "Kimura's disease" in the Orient. A similar lesion was described in the English literature for the first time by Wells and Whimster. Following this, a few reports on these lesions have been published in the West., , , , , 
A thorough search of literature does not bring any case to light reported so far from India and hence this case report.
A thirty-five year old Muslim female attended the out-patient department with the complaint of a gradually increasing painless swelling in the left frontal region of one year's duration. The skin over other parts of her body did not show any abnormality. She did not give a positive history for fever, skin rashes, asthma and respiratory infection, nor any history of louse infestation of the scalp sine: childhood. On clinical examination there was no evidence of lymphadenopathy or hepatosplenomegaly. The scalp on the left frontal region showed a tumour mass, 3 cm x 2.5 cm x 1 cm in size, firm in consistency and subcutaneous in situation. The swelling was non-tender with restricted mobility. Clinical impression of dermoid cyst of the scalp was made.
Chest screening showed no abnormality; haemoglobin was 11 gm%. Total leucocyte count was 10,000/mm3, with P-54%, L-40% and E-6%. Besides these, no other clinical investigations were done.
Complete surgical excision of the nodule was performed and the specimen was examined histopathologically.
The patient has not sought medical attention again ever since the healing of her surgical wound.
Formalin (10%) fixed, whitish tumour tissue was received. The size of the tumour was 2.5 cm x 2 cm x 1 cm. The external surface was smooth. On cut surface, the tumour showed fine whitish capsule surrounding pale pink areas with a few pin-point haemorrhages.
On routine H. & E. staining, the tumour revealed an oedematous capsule with plasma cell and eosinophilic aggregates around its capillaries. The rest of the tumour showed three distinct components:
(1) Mesenchymal stroma with dense eosinophilic, plasma-cell and lymphocytic infiltrate.
(2) Attempted formation of a few lymphoid follicles near the periphery of the lesion and absence of lymph sinuses.
(3) A remarkable proliferation of small blood vessels throughout the lesion [Fig. 1].
Towards the periphery, the blood vessels appeared smaller and more organized with a single layer of endothelium lining their lumina. Towards the central core, the blood vessels showed branching and irregular larger stellate lumina. Here the lining endothelial cells were plump, frighteningly bizzarre, arranged in multiple layers and cords [Fig. 2]. Individual endothelial cells showed abundant pink cytoplasm; the nuclei though large were reniform, vesicular with single nucleoli and distinct nuclear membrane [Fig. 2]. There was no evidence of abnormal nuclear mitosis. The lumina of the blood vessels appeared almost empty; only an occasional one showed the presence of erythrocytes.
Elastic Van Gieson stain showed absence of elastic fibres in the blood vessel wall, with a few collagen fibres in the vessel walls and the stroma. Reticulin stain showed abundant reticulin around blood vessels and endothelial cells but was poor in the germinal centres of the lymphoid follicles. Masson's trichrome was positive for fibrocollagenous tissue in the stroma; the blood vessel wall took up a pink stain indicating smooth muscle properties. Endothelial cells and intervening stroma gave positive Gomori's iron reaction-establishing phagocytosis of haemosiderin by endothelial cells and, stromal histiocytes. Scattered mast cells were seen in the lesion with the help of toluidine blue staining. A diagnosis of angiolymphoid hyperplasia with eosinophilia was made.
Angiolymphoid hyperplasia with eosinophilia is a rare subcutaneous lesion. Histologically it is characterized by vascular and cellular components unique to this lesion alone. Wells and Whimster described two polar types of the lesion-the younger lesions show a predominance of vascular component, whereas the older lesions show predominance of lymphoid follicles. As the lesion ages there is a tendency of lymphocytes to aggregate into foci to form lymphoid follicles towards the periphery of the lesion. This feature is accompanied by maturation of the rapidly proliferating, atypical blood vessels which show progressive thickening of their walls, a reduction in their size and character of the endothelial cells., 
Histopathologic examination of the lesion under discussion showed marked proliferation of the blood vessels in the central core with bizarre appearance of the endothelial cells. Histiocytoid nature of these cells was demonstrated by the presence of haemosiderin in their cytoplasm. These characteristics of the endothelial cells is supported by electron microscopic and light microscopic findings of other authors., , , , 
Benign character of these endothelial cells has been established at ultrastructural level.,  The absence of elastic fibres in our case, with the presence of collagen and smooth muscle indicate that vascular proliferation is not arteriolar in nature. After studying the pericytic and smooth muscle layers in these blood vessels at the ultrastructural level, Wright et. Al have designated these vessels as post-capillary venules and muscular venules.
Local tissue eosinophilia in the lesion along with systemic eosinophilia (6-75%), in some cases is the hallmark of this lesion, yet circumscribed lesion may not always be associated with systemic eosinophilia.,  Our case presented with a well circumscribed tumour with peripheral blood eosinophil count of 6%, but the tumour mass showed a striking eosinophilic infiltrate accompanied with plasma cells, lymphocytes, histiocytes and mast cells, with formation of occasional lymphoid follicles at the periphery.
Total lack of sinus structure in the lesions indicates that these lymphoid follicles arise in the subcutaneous tissue. Considering the two polar types of the lesion postulated by Wells and Whimster, the microscopic appearance of our case can be described as that of mid-polar type i.e. aggressive proliferation of blood vessels in the central portion of the lesion, with marked eosinophilia and plasma cell infiltrate of the mesenchymal stroma, mature small blood vessels at the periphery with the formation of a few lymphoid follicles.
Other lesions that can be confused with ALHE are angiosarcoma in the scalp, eosinophilic granuloma, granuloma faciale, benign lymphocytoma of the skin, angiomatous lymphoid hamartoma and arthropod bite. All above mentioned lesions are histologically and clinically distinct from ALHE., , 
Various speculations have been put forth regarding the nature and histogenesis of the lesion. Some authors believe that it is basically an inflammatory reaction and most histologic differences represent pathologic evolution., ,  Casts et al feel that the lesion is a regenerative change where mesenchymal structures exhibit proliferative healing responses with vascular proliferation as a principle component. It is also speculated that ALHE is an inflammatory reaction, possibly secondary to immunologic injury. As yet there is no definite proof of stimulus like trauma or infection associated with these lesions. In instances where immuno-chemistry has been done, deposition of cryoglobulins, IgG, IgM and IgA is observed in the lesions with elevated levels of these immunoglobulins in the patient's sera. It is proposed that the lesion occurs with greater frequency in atopic individuals like asthmatics. Candida albicans skin testing demonstrates immediate reaction with an elevation of IgE in patients' sera., ,  The presence of systemic eosinophila, tissue mast cells and eosinophils also suggests type I hypersensitivity. Other authors speculate that ALHE is a true- benign tumour, with an accompanying inflammatory cell infiltrate., ,  Rosai and associates have called the tumour histiocytoid haemangioma. Regression of the lesion has been noted following surgical excision, local irradiation and systemic corticosteroid therapy, as seen in true benign neoplasms. Instances of recurrences are reported but never with fatal outcome.
We also agree with these authors and support their view that ALHE is a benign neoplasm with an inflammatory component. If it were just an exuberant reparative proliferation then the lesion should be replaced by excessive fibrocollagenous tissue or regress on its own after the stimulus exciting such a proliferation has abated. Multicentricity of the lesion and its occasional tendency to recur also points towards its neoplastic nature, albeit with an inflammatory component.
We thank Dr. B. R. Kalke, M.S. Dean, L.T.M. Medical College and Hospital for allowing us to publish this case report. Thanks are also due to Mr. C. V. Desai for his assistance with the photographic work.