“A 32 y/o Man with a Soft Tissue
Mass Adjacent to the Right Humerus”
California Tumor Tissue Registry’s
Case of the Month
CTTR COTM Vol. 17:7
April, 2015
www.cttr.org
A 32-year-old man presented with a mass in the right arm. It involved the humerus and
upon excision was 8.2 x 6.5 x 3.5 cm and weighed 52 grams. It consisted mostly of fatty
tissue but had a 3.0 x 2.5 cm, vaguely circumscribed nodule centrally located.
H&E staining of the central lesion revealed marked hyperplasia of lymphoid follicles
with expanded germinal centers and well-formed mantle zones (Fig. 1). Some of the
follicles had intervening fibrosis (Fig. 2). Germinal centers contained lymphocytes
admixed with dendritic cells, polykaryocytes and eosinophilic proteinaceous deposits.
Eosinophils were widely interspersed between the follicles with focal micro-abscess
formation (Fig. 3), or occasionally infiltrated germinal centers with resultant follicular
lysis (Fig. 4). The lesion was well-vascularized. Numerous post-capillary venules lined
by flat endothelial cells were present between follicles and within germinal centers (Figs.
5, 6). Epithelioid endothelial cells were not seen.
Diagnosis: Kimura Disease, arm
Li Lei, M.D., Ph.D. and Donald R. Chase, M.D.
Department of Pathology and Human Anatomy
Loma Linda University Medical Center, Loma Linda, California
California Tumor Tissue Registry, Loma Linda, California
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Kimura disease (KD), named after Kimura for recognizing the vascular component of the
entity in 1948, was first described in China in 1937 by Kim and Szeto as eosinophilic
hyperplastic lymphogranuloma. It is a chronic inflammatory process characterized by
benign reactive lymphoid proliferation with significant eosinophilia, secondary vascular
proliferation and fibrosis.
KD is endemic in Asia, particularly in East and Southeast Asia. Other racial groups
including Caucasian, African American and Hispanic may also be targeted. There is a
striking male predominance with reported male-to-female ratio ranging from 3.5:1 to
19:1. Most of the affected patients are in their twenties to forties.
KD typically presents as a deep subcutaneous mass measuring 2 - 6 cm in size, but giant
tumors up to 13 cm have been reported. Commonly it presents as cervical
lymphadenopathy with a classic example being a peri-auricular mass involving the
parotid gland. Less common sites include the extremities (like our case), axilla, groin,
epiglottis, chest wall, spermatic cord and peripheral nerve.
Laboratory tests usually show peripheral blood eosinophilia and elevated serum
immunoglobulin (IgE). Imaging is usually nonspecific, but sometimes may be seen as
multiple ill-defined, enhancing lesions around the parotid gland with associated
lymphadenopathy.
Clinically, up to 16% of cases are associated with proteinuria, nephrotic syndrome,
membranous glomerulonephritis, bronchial asthma, ulcerative colitis or necrotizing
eosinophilic vasculitis. Patients are otherwise asymptomatic.
Histologically, the tumor consists of dense lymphoid aggregates with prominent germinal
centers, which contain IgE-bearing dendritic reticulum cells, polykaryocytes (WarthinFinkeldey type), nuclear debris and a delicate eosinophilic matrix. Interfollicular dense
eosinophilic infiltrate is a common feature and may form microabscesses. Plasma cells,
small lymphocytes and mast cells are often increased in the paracortex. There is a
moderate proliferation of postcapillary venules which are lined by flat endothelial cells.
Long-standing lesions usually develop hyaline fibrosis and become less vascular.
Affected lymph nodes demonstrate same histologic features with preserved architecture.
The differential diagnosis prominently includes “Epithelioid hemangioma” (EH), also
known as “angiolymphoid hyperplasia with eosinophilia”, a benign vascular neoplasm
which shares many features of KD. Both entities affect young to middle-aged adults,
presenting in the head and neck. Both have an inflammatory component, a vascular
component and increased numbers of eosinophils, but there are differences:
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Parameter Differences:
Kimura Disease (KD)
Epithelioid Hemangioma
(EH)
Race
Asian
Caucasian
Gender
Men
Women
Overlying skin
Normal
Red, pruritic papules
Regional lymphadenopathy
Present
Rare
Peripheral eosinophilia
Present
Rare
Serum IgE
Increased
Normal
Inflammatory component
Prominent
Variable
Germinal center
Expanded
Uncommon
Vascular component
Minor
Major
Endothelial cells
Attenuated
Epithelioid
Despite the above differences (table) these two entities appear intertwined. Some lesions
have characteristic features of both making specific classification almost impossible.
Moreover, KD and EH can coexist in the same patient. Patients with one entity can
develop the other during follow-up. These phenomena suggest that EH and KD may be a
part of a spectrum of reactive vascular lymphoid proliferations.
In addition to EH, other differentials of KD include:



Angioimmunoblastic T cell lymphoma at its early phase can have marked
follicular hyperplasia with germinal centers, eosinophilia and prominent high
endothelial venules. However, patients are often older and present with fever and
generalized lymphadenopathy. Lymph node architecture is usually effaced.
Perivascular clustering of neoplastic clear cells and increased follicular dendritic
cell meshworks are helpful clues. Molecular study shows monoclonal T cell
receptor gene rearrangements in the majority of the cases or IgH rearrangements
in the minority.
Langerhans cell histiocytosis can present as indolent lymphadenopathy in young
adults. Microscopically, lymph node architecture is effaced by mixed infiltrates
of Langerhans cells and eosinophils. CD1a and S100 immunoreactivity help to
confirm the diagnosis.
Follicular lymphoma: Primary cutaneous follicular lymphoma generally affects
the elderly. Follicles consist of predominantly centrocytes with admixed
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
centroblasts. In cases of secondary cutaneous involvement by follicular
lymphoma, a pertinent medical history, back-to-back follicles with no cell
polarization and t(14;18) translocation help reach the correct diagnosis.
Hodgkin lymphoma has a bimodal age distribution with the first peak at 15-35
years of age. Lymph nodes have a “fish-flesh” cut surface. Despite lymphocytes,
eosinophils, and collagen fibers in the background, CD30 and CD15 positive
Hodgkin Reed-Sternberg cells are pathognomonic.
The etiology of KD remains unknown. Multiple clues such as elevated serum IgE,
peripheral eosinophilia and association with other autoimmune diseases favor immune
system hypersensitivity as the underlying pathophysiology. The endemic epidemiology
of KD may reflect either inherent genetic susceptibility or an antigenic trigger unique to
the geographic area.
Patients with KD normally have a favorable outcome. If untreated, the mass may remain
stable or spontaneously regress. The standard care is simple surgical excision. Other
options include laser therapy, radiotherapy and systemic corticosteroids. Local
recurrence rate vary from 14 - 44%. Characteristics which may predict recurrence
include: size ≥ 3.5 cm, peripheral eosinophilia ≥35%, Notch-1 upregulation and Ki-67
proliferation index ≥ 3% outside the germinal center. Metastases are very rare and
therefore anecdotal.
Suggested Reading:
Goldblum J, Folpe A, Weiss S. Enzinger & Weiss’ Soft Tissue Tumors, 6th ed: Philadelphia,
Elsevier Inc, 2014; 649-654.
Rosai J. Rosai and Ackerman’s Surgical Pathology, 10th ed: Philadelphia, Elsevier Inc, 2011;
1805.
Kung IT, Gibson JB, Bannatyne PM. Kimura's disease: a clinico-pathological study of 21 cases
and its distinction from angiolymphoid hyperplasia with eosinophilia. Pathology. 1984;16:39-44.
Deng WY, Ye SB, Luo RZ, Yan SM, Gao YF, Yang YZ, Guo ZM, Chen YF. Notch-1 and Ki-67
receptor as predictors for the recurrence and prognosis of Kimura's disease. Int J Clin Exp Pathol.
2014;7: 2402-10.
Buder K, Ruppert S, Trautmann A, Bröcker EB, Goebeler M, Kerstan A. Angiolymphoid
hyperplasia with eosinophilia and Kimura's disease - a clinical and histopathological comparison.
J Dtsch Dermatol Ges. 2014;12:224-8.
Liu XK, Ren J, Wang XH, Li XS, Zhang HP, Zeng K. Angiolymphoid hyperplasia with
eosinophilia and Kimura's disease coexisting in the same patient: evidence for a spectrum
of disease. Australas J Dermatol. 2012;53:e47-50
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