Castleman ’ s disease

Introduction Castleman’s disease (CD) is a rare benign lymphoproliferative disorder that may present as a nodal or an extra nodal mass. Microscopically, two distinct histological patterns have been described – the hyaline vascular (HV) type or angiofollicular type and the plasma cell (PC) type. CD may be confused with other causes of lymphadenopathy. Although CD is a relatively rare entity, it should be strongly considered in the diff erential diagnosis of cervical lymphadenopathy. In this study, we present a case of CD of HV type involving the right cervical lymph node in an 8-year-old boy.


Introduction
Castleman's disease (CD) is a rare benign lymphoproliferative disorder that may present as a nodal or an extra nodal mass. Microscopically, two distinct histological patterns have been described -the hyaline vascular (HV) type or angiofollicular type and the plasma cell (PC) type. CD may be confused with other causes of lymphadenopathy. Although CD is a relatively rare entity, it should be strongly considered in the diff erential diagnosis of cervical lymphadenopathy. In this study, we present a case of CD of HV type involving the right cervical lymph node in an 8-year-old boy.
A case report An 8-year-old boy was presented with a history of a slowly growing mass on the right side of his neck since 3 years. He was largely asymptomatic except for occasional discomfort around the mass. His past medical and family history was nonspecifi c. On examination, a nontender, fi rm mass was palpated but there was no generalized lymphadenopathy or organomegaly. All his blood results were normal, including those for abnormal hormone production. A CT scan revealed evidence of a well-defi ned, soft tissue mass, seen at the right carotid space. It measured about 3.8 × 2.2 × 2 cm (in L × W × AP, respectively). It had mild homogenous enhancement with no defi nite areas of cystic degeneration inside. It was seen mildly compressing the parotid gland anterolaterally and the carotid vessels medially (Fig. 1).
On complementary US, it appeared as a well-defi ned, oval, soft tissue mass, with rich Dopple r color fl ow inside, which had a main central distribution, these signs mostly suggestive of lymph nodes. Other multiple lesions having the same characteristics but smaller in size were seen at both carotid spaces in the upper and lower neck, posterior triangles, and supraclavicular area, which are suggestive of enlarged cervical lymphadenopathy. Th ere was no specifi c indication in the laboratory tests and imaging examinations; however, MRI/angiography has potential value on clinical and diff erential diagnosis.
A surgical excision of the mass was carried out under genera l anesthesia and the histopathology of the mass showed a hyaline vascular variant o f localized CD (Fig. 2). An extended immunostain panel includin g CD4 , CD5 , CD20 , CD15 , CD30, plasma marker, kappa and lambda, an d CD68 demonstrated no evidence of clonal lymphoid proliferation. Th e patient was referred to a hematologist. Tests fo r HIV an d

Background and Aims
Castleman's disease is a rare disease of lymph node with two identi ed forms -the hyaline vascular type or angiofollicular type and plasma cell type. It usually presents as localized or systemic lymphadenopathy or even as extra nodal mass and may give rise to several differential diagnoses. Fine needle aspiration cytology (FNAC), as the initial investigation, may be misleading. Excision biopsy usually gives the diagnosis.

Materials and Methods
We report a case of an 8 year old male child who was Presented with a history of a slowly growing mass in his right side of neck for 3 yrs. He Was largely asymptomatic except for occasional discomfort around the mass. His past medical and family history was non-speci c. On examination a non-tender, rm mass Was palpated . Initially Clinically suspected to be lymphoma, but was later histologically con rmed to have Castleman's disease.

Result
We had one case of Castleman's disease which presented as cervical lymphadenopathy of 3 * 2 cms in 8 year child. Patient was mostly asymptomatic with all relevant investigations within normal limits. The cytology ndings mostly showed a predominance of small lymphocytes with capillary fragments. On excision biopsy, the case was diagnosed as Castleman's disease of the hyaline vascular type.
huma n herpesvirus (HHV8) were carried out, both of which were negative. Th e patient was asymptomatic 12 months postoperatively with no further lymph node enlargement.

Discussion
CD is an uncommon clinicopathological entit y characterized by non-neoplastic lymph node hypertrophy and histologically characterized by angiofollicular lymph node hyperplasia [1]. Castleman et al. [1] fi rst described it in 1956 in a group of patients with localized benign lymphadenopathy.
Th e incidence of CD is not known and can occur at any age, although it has mostly been reported in adults in the literature. Th e etiology of this disease is unknown; however, it has been found in association with Kaposi's sarcoma. Th e synonyms are angiofollicular lymph node hyperplasia, angiofollicular lymphoid hyperplasia, giant lymph node hyperplasia, lymphoid hamartoma, and benign lymphoma.
Clinically, the disease has two forms: localized, as fi rst described by Castleman, which is more common; and multicentric disease (MCD), with involvement of several sites, which was fi rst described b y GABA et al. in 1978 [2].
Histologically, the main types are the HV type and the PC type. Th e HV type is characterized by lymphoid follicular proliferation at diff erent levels of maturity, often forming a layered or 'onion-skin' pattern surrounding a hyalinized vessel at th e center of the follicle. Th ese vessels are often prominent and reactive. Th is is more commonly seen in the localized form of the disease.
Th e PC variant has sheets of mature PCs within the interfollicular tissues surrounding larger germina l centers and having signifi cantly less vascularity. Th e multicentric form of the disease is nearly always associated with this variant. A third histological variant showing a mixed picture can also be seen in MCD.
Th e localized form of the disease s mostly asymptomatic with a single-site lymph node enlargement. Th e sites commonly involved are the abdomen, peripheral lymph nodes, and the mediastinum. It is often discovered incidentally during routine examination, chest radiographs, or because of discomfort secondary to local compression, as is in our case described above. Diagnosis is made by histological analysis of the lymph node biopsy to distinguish it from a thymoma.
MCD, however, presents with systemic symptoms along with multiple lymph node hyperplasia. Th e systemic symptoms are thought to be primarily a consequence of elevated interleukin-6 production. Th ey are present as asthenia, weight loss, fever, and polyadenopathy with a mean of four-site involvement, and are often associated with hepatosplenomegaly.
Some forms of MCD have been found in association with Kaposi's sarcoma, which develops during the clinical course of most HIV-positive MCD cases [3]. An association with HIV-negative Kaposi's sarcoma has also been seen to a much lesser extent. HIV-positive MCD shows an increased prevalence of pulmonary symptoms and can be diff erentiated from other types of HIV-associated systemic lymphoproliferative  Contrast-enhanced axial CT scan shows an evidence of a wellde ned soft tissue mass is seen at the right carotid space. It is seen measuring about (3.8 × 2.2 × 2 cm) in (L × W × AP) respectively. It has mild homogenous enhancement with no de nite areas of cystic degeneration inside. It is seen mildly compressing the parotid gland anterolateral and the carotid vessels medially. disorders. Th ere is also an increased progression of HIV-positive MCD t o HHV8-associated malignant non-Hodgkin's lymphoma [4].
Routine blood tests usually revea l anemia, elevate d ESR, thrombocytopenia, and elevated polyclonal gamma globulins. Identifying an immunophenotypically varied population of B-lymphocytes with polyclonal surface and cytoplasmic immunoglobulin markers helps to confi rm the diagnosis of CD and diff erentiate it from lymphoma [5]. HIV testing should be carried out with the patient's permission . Herpes virus (HHV8/KSHV) has been isolated in almost all cases of HIV-associated Kaposi's sarcoma MCD and some non-HIV Kaposi's sarcoma MCD, prompting tests fo r KSHV 6. Histological examination of the biopsied lymph node is essential for the diagnosis. Th ese fi ndings suggest two possibilities concerning the genesis of CD; the fi rst is the opportunistic presence of HHV8, favored by immune perturbations, and the second is the direct pathogenic role of HHV8, in association with dysregulation of cytokines.
Localized CD usually has a good prognosis and requires surgical excision of the enlarged lymph node with no further treatment. Th e patients generally remain asymptomatic thereafter.
MCD, however, tends to have a variable prognosis with no documented treatment consensus. A variety of combination treatments have been tried with surgical excision, chemotherapy, and steroids. In patients with associated Kaposi's sarcoma, monthly polychemotherapy (e.g. cyclophosphamide, vincristine, doxorubicin, and prednisone) has been tried with limited success. Ant i-IL 6 antibodies have shown success with systemic symptoms, as have steroids. Most treatment modalities involve immunosuppression, increasing the chances of opportunistic infections. Recent suggestions are that treatment with the antiherpesvirus drug ganciclovir or the anti-CD20 B-cell monoclonal antibody, rituximab, may markedly improve outcome [6,7].

Conclusion
Although the best treatment for CD is still unknown, surgical removal of the localized type of the mass has long been considered a standard therapy for the disease. In our patient, a complete surgical excision was accomplished, and, until now, there is no evidence of recurrence .