Epos Kimura's Disease B,J. Parikh*, 8, B, Parikh**, R. M. Jariwala***, N. R, Shah** Assistant Professor, *™ Associate Professor, *** Resident doctor, Pathology Department, **** Professor & Head of department Pathology Department Sheth V.S. General hospital & Smt, N.H.L. Muni. Medical college, Ahmedabad'6 KEY WORDS : Kimura's disease, Eosinophilic lymphadenitis, Lymphadenopathy INTRODUCTION Kimura's disease is a benign chronic inflammatory disorder of unknown etiology that involves the lymphnodes & subcutaneous tissue of head & neck region or the major salivary glands, often associated with regional lymphadenopathy. This is a very rare disease and so a case is reported here. CLINICAL SUMMARY A 20 year old male patient presented with swelling on right side of the neck for 5 months. Systemic symptoms (fever, night sweats & weight loss) were not present, There was no past /family history relevant to tuberculosis. On examination, patient had cervical lymphadenopathy. Haemogram parameters revealed Hb-12.5 g/dl (N: 18.5°18 gidl in men), ‘TC-9200/emm (N: 4500-11000/emm), DO-P: 55% (N: 40-75%), Lt 28 %6( N: 20-45%), E: 15% (N? 1-6%), Mi 02 %,( Ni 210%) Bi 00% (N: 0-1%), Absolute eosinophil count (AEC) was 1350/emm. (N: 40-450/ emm), Biochemical investigations revealed blood urea 25.4 meal (N: 15-45 mg/l) & S. ereatinine 0.8 mg! al (N: 0.61.2 mg/d). Chest X-ray was normal & Mantoux test was negative. HIV antibody screening test was negative (Elisa). FNAC examination revealed moderate cellularity with mixed population of lymphoid cells, histioeytes and many eosinophils. FNA diagnosis of chronic nonspecific lymphadenitis was rendered and the biopsy of the lymphnode was advised to rule out various specific entities associated with dominant eosinophilic infiltration in nodes. Excision biopsy of lymph node was done & sent for histopathological examination. On gross examination, received specimen consisted of lymph node with perinodal adipose tissue ‘measuring 1.5x1x0.5 em. Cut surface of lymphnode was homogenous white, Tissue was processed for routine paraffin embedding, Haematoxylin & Eosin (H & B) stained sections were prepared Microscopic examination revealed preservation of follicular lymphoid architecture with presence of follicular hyperplasia. Interfollicular areas showed ‘massive infiltration of mature eosinophils with presence of eosinophilic microabscesses. Hyalinized vessels were seen in paracortical region. Sclerosis was present. Perinodal adipose tissue possessed lymphoid aggregates with massive eosinophilic infiltrate. Lymphnode & perinodal adipose tissue showed focal evidence of {olliculolysis with infiltration by eosinophils (eosinophilic folliculolysis). Histopathological diagnosis of Kimura's disease was made, Fig-1: Follicular hyperplasia with prominent blood ves- sels in paracortical region (10X, H & E stain) Correspondence address; Dr. Biren J. Parikh 203, 2nd Floor, Shanti Tower, Nr. Tulsi Party Plot, Vasna, Ahmedabad-380007, GMs 74 GUJARAT MEDICAL JOURNAL /AUGUST-9 Vel.64 ¥.2Fig-2: Massive eosinophilic infiltration in interfollicular region (40X, H & E stain) DISCUSSION Kimura's disease was first deseribed in1937 by Kimm & Szeto in the Chinese literature as eosinophilic hyperplastic lymphogranuloma(1) & was later characterized by Kimura et al in 1948 in a manuscript titled "On the unusual granulation combined with hyperplastic changes of lymphatic tissue."(2) ‘The etiology & pathogenesis of Kimura's disease are unknown. The disease is considered as a chronic nonspecific lymphadenitis with presence of numerous cosininophilic infiltrate, also designated under the heading of "eosinophilic lymphadenitis" by some authors.(3) Allergie reactions, & autoimmune reactions with an aberrant immune response have been suggested as possible etiological factors.(4) The findings of increased eosinophils, mast cells, levels of interleukin-5 & IgE suggest an abnormal T'cell stimulation to a hypersensitivity type reaction.(5) Molecular diagnostic studies for immunoglobulin heavy chain & T-cell receptor gene rearrangement in two studies support a reactive nature.(6,7) A case reported by Chim et al(8) describes a clonal T-cell receptor gamma gene rearrangement by polymerase chain reaction (PCR) in an elderly man with Kimura's disease, The clonal T-cell rearrangement was also confirmed by complete sequencing of the VDJ rearrangement. infections Kimura's disease usually presents as solitary or multiple deep subcutaneous nodules, which are slow growing, located in the head & neck. The nodules can be pruritic & painful. This is accompanied by satellite lymphadenopathy and/or salivary gland hypertrophy (mainly parotid & submaxillary glands). Sometimes lymphnode enlargement is the only manifestation of the disease. Other sites of involvement are the oral cavity, groin, limbs, trunk, eyelids, orbit & lacrimal glands. Renal involvement in the form of glomerulonephritis is found in some patients, Cuteneous eosinophilic vasculitis has been reported. Disease is most common in middle aged Asian men, It is seen in an endemic form in Asia (especially in China, Japan) & sporadic in the non- Asian population. The peak age of onset is in the third decade. There is marked male predominance with MIF ratio of 8.5 to 7, Because of the rarity of the disease, its incidence rate & prevalence rate is not known. Blevated serum Igk levels & peripheral blood eosinophilia are commonly present.9 Biopsy is mandatory to the diagnosis, The histopathological examination of involved lymph node reveals a characteristic triad of florid reactive follicular hyperplasia, increased vascularity & marked eosinophilia of the paracortical region.9 Follicular hyperplasia with reactive germinal centres & well formed mantle zones are present. The germinal centres are often well vascularised & contain polykaryocytes (Warthin-Finkeldey type giant cells), proteinaceous deposits & eosinophils. Extensive eosinophilic infiltrate with occasional formation of eosinophilic microabscesses are seen in interfollicular areas, sinusoidal areas, perinodal soft tissue & subcutaneous tissue. Nodal & extra nodal soft tissue lymphoid follicles show folliculolysis with infiltration by eosinophils (eosinophilic folliculolysis). obtain Plasma cells & mast cells are also observed. Hyalinized vessels are seen in paracortical region. Sclerosis of variable degree is often observed which is usually marked in late stage of disease. Immunohistochemical staining with IgE shows a characteristic reticular staining pattern on the processes of follicular dendritic cells of the germinal centres.(9) The differential diagnoses include angiolymphoid hyperplasia with eosinophilia (ALHE), Hodgkin's lymphoma, Langerhan’s cell histiocytosis, Castleman's disease, dermatopathic lymphadenopathy, allergic granulomatosis, drug reaction & parasitic lymphadenitis. The differential diagnosis with ALHE is of particular concern. Kimura's disease & ALHE were often considered GMs 6 GUJARAT MEDICAL JOURNAL /AUGUST-09 Wol.6¢ 80.2identical in the past literature, Despite early statements to the contrary, current evidence strongly suggests that, Kimura's disease & ALHE are different entities. ALHE is a lesion of blood vessels that characteristically involves the skin (not the nodes) of older Caucasian men in the form of multiple small papules or nodules; the head & neck (particularly the periauricular region) being the preferred location.(10) Microscopically, in ALHE, the vascular endothelium may form aggregates & lobules lined by plump epithelioid (histiocytoid) or hobnail endothelial cells which frequently involve large muscular vessels: while Kimura's disease lacks the epithelioid (histiocytoid) character of endothelial cells.(11,12,13,14) Also, regional lymphadenopathy, peripheral blood eosinophilia & elevated serum IgE are uncommon in ALHE. The primary treatment for Kimura's disease is surgical resection. Additional medical therapies including regional & systemic steroid therapy, cytotoxic therapy and radiation have also been employed. The disease has an excellent prognosis, although it may recur locally. Renal involvement in the form of nephrotic syndrome may complicate some of the Juan Rosai Vol: 2, Ackerman’s surgical pathology. edition 1989. Chronic nonspecific lymphadenitis, pp: 1281-1282, Mitsui M, Ogino 8, Ochi K, Ohashi T. Three eases: of eosinophilic Iymphofolliculoid granuloma of the soft tissue originating from the parotid gland. Acta Otolaryngol Suppl. 1996; 522°180-182, Rajpot DK, Pahl N associated with Kimura's disease, Pediatr Nephrol. Clark J. Nephrotic syndrome 2000: 14:486-488, Chim CS, Shek WH, Liang R, Kowng YL. Kimura's diseases of Br J. Opheabimol.1999; 83:878-879, no evidenes of clonality. Jang KA.Ahn SJ, Choi JH ot al. Polymerase chain reaction (PCR) for human herpes virus 8 and heteroduplex PCR for clonality assessment in angiolymphoid hyperplasia with eosinophilia and Kimura's disease. 4 Catan Pathol 01; 28:369-267. Chim C, Fung A, Shek, Lilang R, HO WK, Kowng YL. Analysis of clonality in Kimura's disease. Am {J Surge Pathol.2002; 26:1088-1086. Principles and practice of surgical pathology & eytopathology Steven G Silverberg. Srd edition, Vol: 1, 1997, Kimura's lymphadenopathy, 685-686, CONCLUSION, 10. Castro C, Winkelmann RK. Angiolymphoid Kimura's disease is a rare chronic inflammatory hyperplasia with eosinophilia in the skin, Cancer, disorder of unknown etiology that is most common ovis gectege-170% in middle aged Asian men. It involves the deep subcutaneous tissues & lymph nodes of head & neck 11, Chan JK, Hui PK.Ng CS, Yuen NW, Kung IT, Gwi region with associated regional lymphadenopathy B. Epitheloid Haemangioma (angiolymphoid and/or salivary gland involvement. Histopathological hyperplasia with eosinophilia) & Kimura's Disease examination is diagnostic. Laboratory studies in Chinese, Histopathology, 1989, 16: 557-574 characteristically reveal elevated serum IgE level 12. Googe PB, Harris NL, Mihm MO Jr. Kimura's & peripheral blood eosinophilia, Kimura's disease Disease & angiolymphoid hyperplasia with has a benign indolent course that may wax & wane cosinophilia, Two distinct Histopathological entities over time J Cutan Pathol, 1987, 14:269-271 REFERENCES 18, Kuo TT, Shih LY, Chan HI, Kimura's Disease 1. Kimm HT, Szeto C. Eosinophilic hyperplastic Involvement of lymph nodes & distinetion from lymphogranuloma, comparison with Mikuliey's angiolymphoid hyperplasia with eosinophilia disease (in Chinese). Chin Med J. 1937:23: Am J Surg Pathol, 1988, 12: S4:)-854 699-700, 14. Urabe A, Tsuneyoshi M, Enjoji M. Epitheloid 2% Kimura T, Yoshimura 8, Ishikawa E, On the henateioite aernat,) Kimutitt dineane unusual granulation combined with hyperplastic eee cntholop wate. Aint eae changes of lymphatic tissue, Trans Soe Patho Jpn, toast a71T9 1a, Pathol 1987, 11: 758-766, GMs 76 GUUARKT MEDICAL JOURNAL /AuoUS