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Journal of Reproduction & Contraception
2014 Jun.; 25(2):123-128
doi: 10.7669/j.issn.1001-7844.2014.02.0123
E-mail: [email protected]
Langerhans Cell Histiocytosis on the Vulva: A Case
Report and Review of the Literature
Ning-xia SUN1, Dan CAO2, Qian ZHAO1, Wen LI1
1. Department of Obstetrics and Gynecology, Shanghai Changzheng Hospital, Shanghai 200003, China
2. Huzhou Maternity &Child Care Hospital, Huzhou 313000, China
Langerhans cell histiocytosis (LCH) of the female genital tract is rare. Only 20 cases
of primary vulva LCH have been previously reported in the medical literature. In this
report, we describe an additional case of LCH on the vulva. A 28-year-old Chinese
woman presented with a two-year history of ulcerous lesions on the left vulva. No
associated temperature, tiredness, or general malaise was observed. A diagnosis of
LCH had been made by biopsy. Histological and immunohistochemical findings were
characteristic of LCH. After two weeks of combined medical therapy, including
interferon, prednisone, and methotrexate (MTX), the lesion started to cicatrize. Now,
the patient was well throughout a 18-month follow up, showing no symptoms or signs
of local recurrence or systemic spread. The occurrence of LCH on the vulva is very
unusual. It is necessary to perform a biopsy on the lesion, rule out the possibility of
multiorgan involvement. There are no standard treatment options for this rare disease.
The most effective treatment options remain elusive. In our case, combined medical
therapy was proved to be effective.
Key words: Langerhans cell histiocytosis (LCH); vulva; treatment
Langerhans cell histiocytosis (LCH), also known as Histiocytosis X, is characterized
by an organ-specific infiltration of cells with many morphological features and immunohistochemical markers of Langerhans cells. Clinically, LCH ranges from self-healing lesions to
a multisystem involvement with organ dysfunction resistant to current therapies. The lesions
appear in multiple organs, for example in the bones, skin, and lungs. But genital LCH as the
only manifestation of this disease is very unusual. Initially, Lane et al.[1] reported LCH in a 6year-old child in 1939. We here report an additional case of LCH on the vulva.
Corresponding author: Wen LI; Tel: +86-13601858540; Fax: +86-21-63520020; E-mail: [email protected]
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Case report
A 28-year-old woman, gravida 2, para 1, discovered a ulcerous lesion on her left vulva
in 2009. She felt pruritus in the area sometimes, but had no other cutaneous lesions, and she
had no associated temperature, tiredness, or general malaise. She was given a course of oral
antivirus medicine in local hospital, but the lesions had continued to spread. Physical examination revealed a ulcerous lesion of 1.0 cm 1.5 cm on the left vulva (Figure 1). Regional
lymph nodes were not enlarged.
A diagnosis of LCH had be made in March 2011 after biopsy. Biopsy and histological
findings revealed that the lesions consisted of diffuse infiltrates of Langerhans cells with
indented or grooved nuclei, some of Langerhans cells showed karyokinesis. Various numbers
of eosinophils, lymphocytes, and neutrophils were also present (Figure 2). Immunohistochemical
stains revealed that histiocytic cells were strongly positive for S-100 protein, CD1a, CD68
and vimentin, negtive for HMB-45 (Figure 3). These results led to a diagnosis of LCH.
The tests for the extent of disease including bone marrow biopsy, and PET-CT of bone,
thorax and abdomen, but no abnormalities were detected in any other area. According to
these results, the patient was diagnosed with LCH involving the vulva only.
Because the patient refused surgical excision, we decided to treat her with combined
therapy. The treatment was commenced from April 2011, including interferon, prednisone,
and methotrexate (MTX). The lesion started to cicatrize after two weeks therapy. Now, the
patient was well throughout a 18-month follow up, showing no symptoms or signs of local
recurrence or systemic spread.
Figure 2 A biopsy specimen shows diffuse infiltrates of
Langerhans cells and elevated number eosinophils, lymphocytes and neutrophils also can be
seen (HE 200)
Figure 1 Ulcerous lesion on the left valva ( )
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A: positive for CD1a ( 200); B: strongly positive for S-100 protein, arrow shows tumor embolus in blood vessel
(
400); C: positive for CD68 (
200)
Figure 3 Immunohistochemical results
Discussion
Langerhans cell, also called dendritic antigen presenting cell, is nomal distribution in bone,
lymph node, skin, mucous membrane, and internal organ, especially in skin. Histiocytosis X,
which included Letterer-Siwe’s disease, Hand-Shuller-Christian’s disease, and eosinophilic
granuloma,was renamed Langerhans cell histiocytosis in 1985 by the Histiocytic Society[2].
The diagnosis of LCH has been based on a histopathological pattern in biopsy specimens
showing mono- or multinucleated Langerhans cells, histiocytes, and eosinophils. For a definitive diagnosis of LCH, Birbeck’s granules must be detected by electronic microscopy, or else
the S-100 protein must be found, or the histiocytic cells in lesions consistent with LCH must
be found to be positive for CD1 antibodies[3].
LCH is a very rare disease. The pathogenesis of most histiocytoses remains unclear. A
possible cytokine-related pathway[4] and a potential role of granulocyte-macrophage-colony
stimulating factor (GM-CSF)[5] have been suggested. LCH chiefly affects infants, but may
also occur in adults. An epidemiological study in French showed that the annual incidence
rate is 4.6/106 in children (0 to 14-year-old)[6] and only 1 2/106 in adults[7]. LCH lesions are
common in the bone, lung, skin, liver, spleen, and lymph nodes. In 30.6% of patients, LCH
involved more than one body system. Twenty-five percent of patients had skin and/or mucous
membrane LCH. The most common mucous membranes involved are the genitalia and oral
mucous[8].
Axiotis et al.[9] divided four distinct patterns of LCH involvement in the female genital
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tract: 1) pure genital LCH, in which the disease is limited to the genital tract only; 2) genital
tract LCH with subsequent multiorgan involvement; 3) oral or cutaneous LCH with subsequent genital and multiorgan involvement; 4) diabetes insipidus with organ involvement.
Pure genital LCH on the vulva is very rare. At present, there are only 20 cases reported
in the English literature (Tabel 1). Because the clinical manifestation of genital LCH is not
particular, making a definite diagnosis of this disease is not easy.
Table 1 Cases reported in literature of LCH on the vulva
Report
Voelklein[10]
Axiotis[9]
Weidman[11]
Rose[12]
Saurel[13]
Age (year) Excision Radiotherapy Chemotherapy Others Response
36
+
CR
85
Corticosteroid
NR
27
+
Corticosteroid
CR
Cautery
PR
50
+
PR
91
+
PR
76
Savell[14]
[15] 76
Meehan & Smoller
54
[16]
40
Solano
45
Pather[17]
[18]
33
Santillan
[19]
31
Padula
52
[20]
65
Ishigaki
[21]
41
Dietrich
29
[22]
64
Venizelos
16
Mottl [23]
[24]
49
Beneder
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Thalidomide
Thalidomide
+
+
Corticosteroid
+
CR: complete response
PR: partial response
LTF: lost to follow-up
NEOD: no evidence of disease
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
PR
CR
CR
CR
Outcome (month)
NEOD(12)
LTF
NEOD(156)
LTF
LTF
Die of other
disease
NEOD(8)
NEOD(16)
NEOD(21)
NEOD(24)
NEOD(24)
NEOD(12)
NEOD(19)
NEOD
NEOD(12)
LTF
LTF
NEOD(22)
NEOD(6)
NEOD(51)
NR: no response
Genital LCH should be differentiated by a tissue biopsy from other dermatologic
disorders such as diaper rash, seborrhoea dermatitis, eczema, genital tuberculosis and
sexually transmitted diseases (syphilis, herpes and granuloma inguinale). As in our patient,
HPV and syphilis antibody had been tested. Several neoplastic processes can also resemble
LCH, including squamous cell carcinoma, malignant melanoma, sarcoma and Paget’s disease
of the vulva[23].
The diagnosis of LCH is performed by tissue biopsy only. For ruling out multiorgan
involvement, the routine evaluation should include bone marrow biopsy, chest X-ray, CT of
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the abdomen and pelvis, and a bone scan. We used PET-CT to scan total body, also could
confirm the range of lesion.
Because of the small number of cases reported, there is no standard recommendation
for the management of genital LCH. Methods of treatment primarily included surgery,
radiotherapy and chemotherapy. Other forms of treatment have also been used including
topical corticosteroids, topical nitrogenated mustard, thalidomide, or combined therapy. Axiotis
et al.[9] suggested treating genital lesions initially by complete excision, but 50% of the patients
with genital LCH relapsed after surgery [25]. Radiotherapy and chemotherapy were
demonstrated to be benefical in several cases. Thalidomide was also used in two cases of
genital LCH with good results; this may have been due to its action on TNF-α[26].
Chemotherapy for multisystem disease is beneficial[14], but there are few data referring
to the use of chemotherapy for very localized disease. Systemic treatment with vincristine
did not clear up the lesions of the patient described by Solano et al.[16], and after the surgical
excision, the patient remained cured. The patient that was treated according to the LCH II
protocol with vinblastine and prednisone by Mottl et al.[27] relapsed as well after 8 months and
received a second-line treatment with 2-chlorodeoxyadenosine. Eighteen months later she
still has no sign of recurrence. In our patient, we suggested complete excision initially, but the
patient refused. Then we decided to treat her with combined therapy. The medical scheme
was commenced from April, including interferon 3 106 IU ih. 3 times a week, prednisone
15 mg po. bid, and MTX 5 mg po. 2 times a week. The lesion started to cicatrize after two
weeks therapy. Now, the patient was well throughout a 18-month follow up, showing no
symptoms or signs of local recurrence or systemic spread. Because the prognosis is unknown,
we will continue to follow the patient closely.
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(Received on May 28, 2014)
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