Sinus histiocytosis with massive lymphadenopathy (SHML)
also known as Rosai-Dorfman disease, is first reported in
1969 (1). SHML is usually seen in the first and second decade
of life, with no specific gender, ethnic or socioeconomic pre-
dilection. Painless lymphadenopathy is the most frequent
presenting symptoms and involved the cervical lymph node
in up to 90% of patients. In approximately 40% of patients,
extranodal lesions in the skin and soft tissues, upper respira-
tory tract, genitourinary tract, oral cavity, kidney, thyroid,
breast, and bone can be found (2). Typically, the lymph node
sinuses are expanded by a proliferation of histiocytes with
abundant pale eosinophilic cytoplasm containing emperipole-
sis (3, 4). The S-100 stain is helpful in identifying the histi-
ocytes of SHML (5). There is no specific treatment for the
SHML. We report a case of a young man who was diagnosed
with SHML involving cervical lymphadenopathy and pleu-
A 26-yr-old man presented with a firm, nontender palpa-
ble lymph node in his left cervical area. The patient had no
specific past medical history. On admission his blood pres-
sure was 120/80 mm Hg, pulse rate 80/min, respiratory rate
24/min, and body temperature 36.5℃. Routine laboratory
investigations showed a normal complete blood count, serum
chemical tests, and erythrocyte sedimentation rate (ESR).
Serologic tests for cytomegalovirus, human immunodeficien-
cy virus (HIV) and polymerase chain reaction (PCR) analysis
of mycobacteria yield negative results. Serum immunoglob-
ulin (Ig) levels were as follows: IgG, 1,680 mg/dL (normal
700-1,700 mg/dL); IgA, 117 mg/dL (normal 70-400 mg/dL);
IgM, 129 mg/dL (normal 40-230 mg/dL); and IgE, 33.8 IU/
mL (normal 0-100 IU/mL). Computed tomography of the
chest showed mediastinal lymph nodes with calcification and
pleural effusion (Fig. 1). Diagnostic thoracentesis was not
performed because of scanty pleural effusion. Excisional biop-
sy of the cervical lymph node revealed dilated sinuses filled
with histiocytes with abundant pale eosinophilic cytoplasm
(Fig. 2). The histiocytes were positive immunoreactivities
for CD68 and S-100 protein (Fig. 3). These findings were
diagnostic of SHML. The patient had received prednisolone
therapy (30 mg per day, PO). On follow-up the patient was
well without symptoms and signs.
Sinus histiocytosis with massive lymphadenopathy is a
Jinyung Ju, Yong Soo Kwon,
Kae Jung Jo, Dong Ryeol Chae,
Jung Hwan Lim, Hee Jung Ban,
Su Young Chi, In Jae Oh,
Ku Sik Kim, Yu Il Kim,
Young Chul Kim, and Sung Chul Lim
Department of Internal Medicine, Chonnam National
University Hospital, Gwangju, Korea
Address for correspondence
Sung Chul Lim, M.D.
Department of Internal Medicine, Chonnam National
University Hospital, 8 Hak-dong, Dong-gu, Gwangju
Tel : +82.62-220-6570, Fax : +82.62-225-8578
E-mail : firstname.lastname@example.org
J Korean Med Sci 2009; 24: 760-2
Copyright � The Korean Academy
of Medical Sciences
Sinus Histiocytosis with Massive Lymphadenopathy: A Case Report
with Pleural Effusion and Cervical Lymphadenopathy
Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder char-
acterized by a nonneoplastic proliferation of distinctive histiocyte cells within lymph
node sinuses and lymphatics in extranodal sites. SHML occurs worldwide and is
primarily a disease of childhood and early adulthood. A 26-yr-old man presented
with painless palpable lymph node in cervical area. Radiographic studies revealed
pleural effusion with lymphadenopathy and calcification in mediastinum. The cervi-
cal lymph node biopsy showed dilated sinuses filled with histiocytes with clear cyto-
plasm. The cells stained positive with CD68 and S-100. These cytologic and imm-
unohistochemical findings were considered consistent with the diagnosis of SHML.
Key Words : Histiocytosis, Sinus; Massive Lymphadenopathy; Rosai-Dorfman Disease
Received : 25 July 2007
Accepted : 27 April 2008
Sinus Histiocytosis with Massive Lymphadenopathy761
rare disorder characterized by a nonmalignant proliferation
of histiocyte within lymph node sinuses and lymphatics in
extranodal sites. There is no evidence to support immunod-
eficiency, autoimmune disease or a neoplastic process for the
etiology of the disorder. An association with Epstein-Barr
virus (EBV), cytomegalovirus (CMV), Brucell, Klebsiella,
or human herpes virus 6 has been suggested but not proven
(6-8). Serologic tests for CMV, HIV, and PCR of mycobac-
teria were negative in our patient.
Most patients with SHML tend to have a chronic massive
enlargement of cervical lymph nodes frequently accompanied
by fever, elevated ESR, neutrophilia, polyclonal gammopa-
thy (9). Our patient had no history of fever and laboratory
investigations showed a normal complete blood count, ESR,
immunoglobulin levels.Extranodal disease is seen in approx-
imately 30% of patients. The most often affected extranodal
sites include skin and soft tissues, upper respiratory tract,
orbit, testicle, kidney, thyroid, small bowel, breast, and bone
(2). Hepatosplenemegaly is uncommon.
Typical histopathologic findings of SHML are large poly-
clonal histiocytes with abundant pale, eosinophilic cytoplasm
and display emperiopolesis. Mitoses are infrequent, although
increased mitotic activity can be apparent occasionally (3, 4,
SHML involving extranodal sites shows similar morpho-
logic features to its nodal counterpart although more fibro-
Fig. 1. Chest CT revealed pleural effusion and mediastinal lymph-
Fig. 2. Excisional biopsy of the cervical lymph node revealed dilat-
ed sinuses filled with histiocytes with abundant pale eosinophilic
cytoplasm (arrows) (H&E, ×400).
Fig. 3. Immunohistochemical staining for CD68 and S-100 protein. Histiocytes show positive immunoreactivity with brown color for CD 68
(A, ×400) and S-100 (B, ×400).
762J. Ju, Y.S. Kwon, K.J. Jo, et al. Download full-text
sis and fewer histiocytes with emperiopolesis are encountered.
The most useful immunohistologic marker for SHML histi-
ocytes is the expression of the S-100 protein (11, 12). In addi-
tion, SHML histiocytes stain for CD68, CD64, alpha-1 antit-
rypsin, and interleukin-2 receptor and are negative for CD1a
(5, 13, 14).
The clinical course of SHML is characterized by sponta-
neous resolution in most cases. There is no specific treatment
for the SHML. Treatment is required when the condition is
organ threatening or life threatening. For patients with high
fever without other symptomatology steroid therapy may be
instituted. Surgical debulking may be used in cases where
vital organ function is compromised. The role of additional
therapies, such as chemotherapy or radiation therapy, is min-
imal. However all patients deserve long-term follow-up, since
the natural history of the disease is quite variable, usually
alternating periods of exacerbations and resolutions or, rarely,
pursuing a progressive course.
1. Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopa-
thy. A newly recognized benign clinicopathological entity. Arch Pathol
1969; 87: 63-70.
2. Tiju JW, Hsiao CH, Tsai TF. Cutaneous Rosai-Dorfman disease:
remission with thalidomide treatment. Br J Dermatol 2003; 148:
3. Pettinato G, Manivei JC, d’Amore ES, Petrella G. Fine needle aspi-
ration cytology and immunocytochemical characterization of the hi-
stiocytes in sinus histiocytosis with massive lymphadenopathy (Rosai-
Dorfman syndrome). Acta Cytol 1990; 34: 771-7.
4. Chan JK, Tsang WY. Uncommon syndromes of reactive lymphade-
nopathy. Semin Oncol 1993; 20: 648-57.
5. Bonetti F, Chilosi M, Menestrina F, Scarpa A, Pelicci PG, Amorosi
E, Fiore-Donati L, Knowles DM 2nd. Immunohistological analysis
of Rosai-Dorfman histiocytosis. A disease of S-100+CD1-histiocytes.
Virchows Arch A Pathol Anat Histopathol 1987; 411: 129-35.
6. Ahsan SF, Madgy DN, Poulik J. Otolaryngologic manifestations of
Rosai-Dorfman disease. Int J Pediatr Otorhinolaryngol 2001; 59:
7. Paulli M, Bergamaschi G, Tonon L, Viglio A, Rosso R, Facchetti F,
Geerts ML, Magrini U, Cazzola M. Evidence for a polyclonal nature
of the cell infiltrate in sinus histiocytosis with massive lymphadenopa-
thy(Rosai-Dorfman disease). Br J Haematol 1995; 91: 415-8.
8. El Kohen A, Planquart X, Al Hamany Z, Bienvenu L, Kzadri M, He-
rman D. Sinus histiocytosis with massive lymphadenopathy (Rosai-
Dorfman disease): two case reports. Int J Pediatr Otorhinolaryngol
2001; 61: 243-7.
9. Karpas A, Worman C, Arno J, Nagington J. Sinus histiocytosis with
massive lymphadenopathy: virological, immunological, and morpho-
logicalstudies. Br J Haematol 1980; 45: 195-200.
10. Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lym-
phadenopathy (Rosai-Dorfman disease): review of the entity. Semin
Diagn Pathol 1990; 7: 19-73.
11. Eisen RN, Buckley PJ, Rosai J. Immunophenotypic characterization
of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman
disease). Semin Diagn Pathol 1990; 7: 74-82.
12. Paulli M, Rosso R, Kindl S, Boveri E, Marocolo D, Chioda C, Agos-
tini C, Magrini U, Facchetti F. Immunophenotypic characterization
of the cell infiltrate in five cases of sinus histiocytosis with massive
lymphadenopathy (Rosai-Dorfman disease). Hum Pathol 1992; 23:
13. Deshpande V, Verma K. Fine needle aspiration (FNA) cytology of
Rosai Dorfman disease. Cytopathology 1998; 9: 329-35.
14. Ruggiero A, Attina G, Maurizi P, Mule A, Tarquini E, Barone G,
Lazzareschi I, Riccardi R. Rosai-Dorfman disease: two case reports
and diagnostic role of fine-needle aspiration cytology. J Pediatr He-
matol Oncol 2006; 28: 103-6.