ARTICLE
Auteur(s) : Brigitte Coras1, Susanne
Michel2, Michael Landthaler1, Ulrich
Hohenleutner1
1Department of Dermatology, University of Regensburg,
Franz-Josef-Strauß-Allee 11, 93047 Regensburg, Germany
2Private Practice, Landshut, Germany
accepté le 26 Octobre 2005
In 1969, Rosai and Dorfman first described a new entity named sinus
histiocytosis with massive lymphadenopathy, mostly in cervical
localisation [1]. RDD is a rare, self-limited disease, a distinct
entity within the spectrum of histiocytic disorders of unknown
origin. Mostly it occurs solely as a nodal manifestation, but
additional extranodal manifestation is possible. The most common
extranodal site of RDD is the skin. Cutaneous lesions and
lymph-nodes show characteristic histologic findings.We report the
case of an elderly woman which fulfils clinically and
histologically the features of RDD.
Case report
A 73-year-old female presented massive cervical lymphadenopathy on
the right side. The lymphadenopathy had been present since her
childhood. Additionally, she had complained for 2 years about
cutaneous lesions on her face, collum, neck and upper chest. Over
the past years, she had experienced several periods of fever
without any overt reason. During these times, skin lesions had
appeared and some of the lesions had become elevated. Some papules
had undergone transient regression only to recur after some time.
The patient reported neither anorexia nor weight loss. In 1995 and
1996, she had had an extirpation of a cervical lymph node of the
right side under the clinical diagnosis of sarcoidosis. The
histological specimens were not typical for sarcoidosis and
acid-fast bacteria could not be found. Due to a strongly positive
Tine test, she had received isoniazid and vitamin B6 for
12 weeks under the clinical diagnosis of tuberculosis, which did
not lead to any improvement.
Examination revealed a massive, non-tender enlargement of the
lymph nodes on the right side of the neck. Several sharply
demarcated, round to oval, red-brown, non-tender macules and
nodules up to 1 cm in diameter were observed on the face,
collum and neck (figure
1). These nodules were purely cutaneous without palpable
infiltration of the underlying subcutaneous tissue. No other lymph
nodes were palpable. The further results of the physical
examination were unremarkable.
Excision biopsy of a nodule on the neck and of a cervical lymph
node was performed under local anaesthesia with 1% prilocaine.
The skin biopsy specimen of the neck showed an inflammatory
infiltrate in the upper and middle dermis with numerous plasma
cells and a large number of histiocytoid cells, some of them
showing large, pleomorphic and multiple nuclei. Within the
cytoplasm of these cells, other cells were engulfed, including
neutrophiles and lymphocytes (emperipolesis) (figure 2). These findings
are consistent with the diagnosis of RDD.
The cervical lymph node biopsy likewise showed massive sinus
infiltration by macrophages and lymphocytes (emperipolesis) (figure 3).
The histocytoid cells stained positive for S100, CD68, CD45RO
and factor XIIIa and negative for CD 30, CD 20 and CD1a, also
underscoring the above diagnosis.
Routine laboratory work was within normal limits except for
creatinine (1.06 mg/dL), uric acid (6.72 mg/dL), cholesterol (238
mg/dL), ferritin (160 ng/mL), MCH (27.3 pg) and MCHC (31.3 g/dL). A
normal sedimentation rate and normal values for calcium, ACE, IgG,
IgM, IgA and IgE were noted. The tine tuberculin test was strongly
positive. Multiple specimens of urine, gastric acid and sputum were
examined microscopically, by cultivation and by polymerase chain
reaction excluding acid-fast bacteria. Serologic tests for
toxoplasmosis, brucellosis and HHV 6 – infection were negative.
The chest x-ray showed postspecific changes but no evidence of
mediastinal involvement. There was no evidence of spleno- or
hepatomegaly. Lymph-node sonography (7.5 MHz) of the right
neck showed large hypoechoic, oval structures up to 2 cm in
diameter within a normal lymph node architecture as well as
hypoechoic, round structures with a loss of the normal lymph node
architecture (figure
4).
Topical glucocorticoids led to some improvement but after
discontinuation, the lesions recurred. Until now, full remission of
the skin lesions and the nodal involvement could not be
achieved.
Discussion
RDD can occur as both nodal and/or extranodal disease. In 95%, the
disease is associated with cervical, massive and often bilateral
lymphadenopathy and in 80%, axillary, inguinal and mediastinal
lymph nodes are affected, too. In 30-43% of all reported cases,
extranodal manifestations have been described in addition to a
nodal involvement [2-5]. The orbita, upper lid, upper respiratory
tract, salivary glands, breast, bones, skin, testis, epidural
space, spinal column, genitourinary system and digestive system can
be affected [6-9]. Skin lesions occur in 11-27% of all reported
cases with lymph node involvement, are the most common extranodal
manifestation and may represent the first manifestation of the
disease [5, 10]. Purely cutaneous lesions in RDD have been reported
only in 29 patients. Purely cutaneous RDD is a distinct clinical
entity and remains localized to the skin even with long-term
follow-up. Clinically, the skin lesions of RDD are variable, mostly
presenting as papules, nodules or plaques, infrequently also as
pustular and acneiform lesions. The lesions can resemble,
Langerhans cell disease, miliary tuberculosis or sarcoidosis, the
latter being the case in our patient. The lesions show a
predilection for the neck and upper trunk and can appear single or
multiple [11-13].
Symptoms of systemic disease like fever, raised erythrocyte
sedimentation rate, anaemia, leukocytosis, hypergammaglobulinemia,
antinuclear antibodies, glomerulonephritis, arthritis and
Wiskott-Aldrich Syndrome can additionally be present [2, 14, 15].
Often RDD starts with chronic rhinitis.
The RDD lesions are metabolically highly active. PET-imaging
shows a high FDG-uptake within the granulomatous tissue with more
intense metabolism within lymphocyte follicles [16].
Histologically, RDD is characterized by a nodular, poorly
defined polymorphous infiltrate in the upper and middle dermis
composed of histiocytoid cells. Some of the histiocytoid cells show
large, pleomorphic and multiple nuclei and a pale cytoplasm.
Typically some cells are cytophagocytic for lymphocytes, which is
called emperipolesis. Extranodal RDD can also be diagnosed by fine
needle aspirate in conjunction with immunocytochemistry [17,
18].
The aetiology of RDD is still unknown. Infectious and
autoimmunologic processes or immunodeficiency have been discussed
as a cause of for RDD. Various authors describe raised antibody
titers for Epstein-Barr-Virus (EBV), human papilloma virus (HPV),
Rubella virus, Klebsiella, human herpes virus 6 (HHV6) and atypical
mycobacterial infection in HIV patients possibly associated with
RDD [19-21]. Others suggested that RDD lesions derive from the
accumulation of monocyte-like cells [5] in tissue, which locally
undergo a terminal differentiation and acquire a unique phenotype.
Innocenzi et al. found that about 20% of lesional cells with
macrophage morphology stained positively for vitronectin receptor
avb3 and more than 90% of them were positive for ICAM-1 and for
beta1 and beta2 integrins. The expression of adhesion molecules
might be involved in the phenomenon of cytophagocytosis or
emperipolesis [5].
Mostly RDD runs a chronic course, is asymptomatic and does not
require treatment since it is a benign disease with a tendency
towards spontaneous regression after months or years. The
association of RDD with cancer is unclear, but single cases
indicate that a closer follow-up of RDD patients in order to
diagnose associated malignancies as early as possible seems
warranted [22]. In some cases multiple organ involvement and
systemic symptoms have been described [2, 3, 5, 15]. In the
presence of vital organ compression and/or extranodal localization
with important clinical signs, surgical debulking may be necessary
[23]. In cases with cosmetically unacceptable skin lesions or in
cases of rapid progression, excision, x-ray, cryotherapy,
thalidomide and isotretinoin may be successful [2, 5, 11, 24, 25].
Satter et al. reported a response with 0.05% clobetasol propionate
ointment and 0.1% adapalene gel for thin cutaneous lesions and
intralesional steroids for more nodular areas in patients who
desired treatment for limited, nonlife-threatening cutaneous
disease [26]. Various other therapeutic modalities have been
described including methotrexate, mercaptopurine, vinca alkaloids,
α-interferon and glucocorticosteroids in combination with
vinblastine [7, 27, 28], which can probably improve lymph node
involvement. Excision combined with chemotherapy may be warranted
in full-blown and distinct cases [5]. RDD can be associated with or
mimic severe SLE. Petschner et al. described a response to
rituximab, an anti-CD20 monoclonal antibody which may improve the
antibody-mediated pathogenic mechanism underlying both entities
[29].
RDD is a rare but important differential diagnosis in swelling
of cervical lymph nodes. Lyme disease, Hodgkin’s disease, lymph
nodes in cutaneous malignant lymphomas, metastases of other
malignancies and various other infectious diseases can cause
swelling of cervical lymph nodes.
Our patient, clinically as well as histologically, fulfils the
typical findings of RDD including massive, painless
lymphadenopathy, fever and cutaneous lesions with an macrophages
infiltration showing emperipolesis.
Unusual in our case was the late onset of the skin lesions which
appeared approximately 60 years after the cervical node
swelling.
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