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Vulvar plasmablastic lymphoma in a HIV-positive child: a novel extraoral localisation
  1. P Chabay1,
  2. E De Matteo2,
  3. M Lorenzetti1,
  4. M Gutierrez3,
  5. M Narbaitz4,
  6. L Aversa3,
  7. M V Preciado1
  1. 1
    Molecular Biology Laboratory, Pathology Division, Ricardo Gutiérrez Children’s Hospital, Buenos Aires, Argentina
  2. 2
    Pathology Division, Ricardo Gutiérrez Children’s Hospital, Buenos Aires, Argentina
  3. 3
    Hematolgy Unit, Ricardo Gutiérrez Children’s Hospital, Buenos Aires, Argentina
  4. 4
    Mariano R Castex Hematology Research Institute, National Academy of Medicine, Buenos Aires, Argentina
  1. Dra Paola A Chabay, Laboratorio de Biología Molecular, División de Patología, Hospital de Niños R Gutiérrez, Gallo 1330, C1425EFD, Buenos Aires, Argentina; paola_chabay{at}yahoo.com.ar

Abstract

Plasmablastic lymphoma (PBL) has been characterised by the World Health Organization as a new entity. This report describes an unusual case of PBL in a 3-year-old HIV-infected patient showing a cutaneous vulvar lesion with 9 months of evolution and prolapsed vulvovaginal mucosa. Histopathological examination of a biopsy sample showed diffuse submucosal infiltration by large cells with a cohesive growth pattern, and round and vesicular nuclei with fine chromatin centrally or eccentrically placed with one or more prominent nucleoli. Immunohistochemical staining in neoplastic cells was positive for multiple melanoma oncogene (MUM1), CD138, CD45 and epithelial membrane antigen (EMA). The diagnosis was PBL, stage III. Epstein–Barr virus (EBV) expression was positive by EBV encoded RNAs in situ hybridisation. This is believed to be the third case of paediatric HIV-associated PBL reported in the literature, and the first with vulvar localisation, which is a new anatomical location for this entity.

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In 1997, Delecluse et al1 described an AIDS-associated B lineage neoplasm with plasmacytic differentiation typically presented in the oral cavity, and they proposed it as a new subtype of diffuse large B cell lymphoma: plasmablastic lymphoma (PBL). PBL is classified by the World Health Organization as a distinct type of non-Hodgkin lymphoma.2 Previous reports have described that PBL has heterogeneous cytological findings, with a differentiated B cell or plasma cell immunophenotype, characterised by weak or absent expression of B cell markers, and expression of the following postgerminal centre B cell associated and plasma cell associated markers: multiple melanoma oncogene (MUM1)/interferon regulatory factor 4 (IRF4) and CD138/syndecan-1.1 3 PBL is commonly seen in adults and has a predilection for the oral cavity.4

Lymphomas in HIV-positive patients are often associated with Epstein–Barr virus (EBV); they include AIDS-associated immunoblastic lymphoma (100%), Burkitt lymphoma (40%) and PBL of the oral cavity (74%).5 6

We describe an unusual case of PBL in a HIV-infected child showing a cutaneous vulvar lesion with 9 months of evolution and prolapsed vulvovaginal mucosa.

CASE REPORT

A 3-year-old HIV-positive girl presented for evaluation of a cutaneous vulvar lesion with 9 months of evolution and prolapsed vulvovaginal mucosa. Physical examination revealed an asymptomatic erythematous–oedematous–infiltrative vulvar plaque. The patient was afebrile, with neither palpable lymph nodes nor hepatosplenomegaly. Genitourinary and rectal tracts showed a tumour (10×8 cm).

Laboratory values at admission included: white blood cell count 3.9×109/l, haemoglobin concentration 118 g/l, and platelet count 277×109/l. HIV viral load at admission was >750 000 copies/ml concomitant with a CD4 cell count of 285 cells/mm3. An antiretroviral therapy regime with stavudine, lamivudine and efavirenz was commenced. Bone marrow aspirate and biopsy at that time were normal.

Abdominal CT imaging revealed a 15 mm hypodense mass in the liver as well as a perirectal left mass, along with enlarged retroperitoneal lymph nodes, involving iliac nodal chain (fig 1). Brain and thoracic CT scans were normal.

Figure 1

CT scan of pelvis showing a voluminous perirectal left mass (30×20×15 mm in size).

MATERIALS AND METHODS

An incisional biopsy of a greyish irregular vulvar lesion was obtained. Formalin-fixed, paraffin-embedded tissue sections were stained with H&E and periodic acid–Schiff and examined.

Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections with a panel of monoclonal antibodies: human muscle actin (HHF35), desmin, MyoD1, myogenin, vimentin, cytokeratin AE1/AE3, HMB45, CD45, CD20, CD3, CD79a, CD138, VS38C, MUM1, epithelial membrane antigen (EMA), Ki67 and Bcl6 (Dako, Glostrup, Denmark); CD30 and Bcl2 (Biogenex, San Ramon, California, USA); CD10 (Santa Cruz Biotechnology, Santa Cruz, California, USA); S100 (Abcam, Cambridge, UK).

EBV expression was assessed by EBV-encoded RNAs (EBERs) in situ hybridisation on formalin-fixed, paraffin-embedded tissue section using fluorescein isothiocyanate (FITC)-conjugated EBERs oligonucleotides as probes.

RESULTS AND DISCUSSION

The presumptive clinical diagnosis in this particular localisation and age group was rhabdomyosarcoma and, considering that the patient was HIV positive, lymphoma was also thought about.

Histopathological examination of the biopsy showed diffuse submucosal infiltration by large cells with a cohesive growth pattern, round and vesicular nuclei with fine chromatin, either centrally or eccentrically placed with one or more prominent nucleoli. Cells also had slight nuclear pleomorphism, moderate to abundant basophilic cytoplasm and high numbers of mitosis (fig 2A). The histological review made us also consider entities other than rhabdomyosarcoma and lymphoma, such as carcinoma or melanoma, which need further immunophenotypical characterisation.

Figure 2

(A) Section showing a submucosal proliferation. Neoplastic cells have moderately clumped chromatin, a single prominent nucleolus, moderate to abundant cytoplasm and starry sky pattern (H&E, ×100). (B) CD45 immunohistochemical expression in membrane of neoplastic cells (×600). (C) CD138 immunohistochemistry for plasma membrane antigen CD138 stained positive in membrane of tumour cells (×600). (D) Epstein–Barr virus (EBV)-encoded RNAs in situ hybridisation for EBV shows positive staining in the nucleus of neoplastic cells (×600).

Immunophenotype analysis and differential diagnosis are compiled in table 1.

Table 1 Differential diagnosis of plasmablastic lymphoma

Immunohistochemical staining revealed MUM1 and CD138 positive staining in neoplastic cells, while CD45 and EMA were weakly positive (figure 2B, C; table 1). The immunophenotype of PBL is characteristically negative for CD20, but positive for plasma cell markers such as CD138 and MUM1.1 Other authors have previously described variable EMA positivity in neoplastic and non-neoplastic plasma cells7 and either weak or no expression of CD45 in PBL.1 All tumour cells proved to be negative for B cell and T cell markers such as CD20, CD10 and CD3 and for the pre-B cell marker Cd79a (table 1). The Ki67 proliferation index was nearly 70%. These immunohistochemical findings along with histology were consistent with a diagnosis of PBL. This changed the AIDS category of the patient from A2 to C3.

The most frequent vulvovaginal tumour in paediatric patients is rhabdomyosarcoma, and so differential diagnosis with this entity was assessed. Expression of muscle specific actin (HHF35), desmin, Myo D1 and myogenin turned out to be negative. Cytokeratin negative expression, together with absence of HMB45 and S100, ruled out carcinoma and melanoma diagnosis, respectively (table 1).

EBV is associated with different tumour types, including endemic Burkitt lymphoma and B lymphoproliferative disease in immunocompromised hosts, Hodgkin lymphoma and nasal natural killer (NK)/T cell lymphoma. EBV is found in 60% of HIV-associated lymphomas, namely: primary central nervous system lymphoma (100%), Hodgkin lymphoma (∼100%), primary effusion lymphoma (90%), the immunoblastic variant of diffuse large B cell lymphoma (80%) and Burkitt lymphoma (30%).8 Although PBL cases have been reported in immunocompetent individuals as well as in immunosuppressed patients in the post-transplant setting, the vast majority of PBL cases are seen in patients with chronic HIV infection.6 In HIV-related PBL, Castillo et al have reported the presence of EBV in 74% of published cases.6 Our case also exhibits EBV expression by EBERs in situ hybridisation (fig 2D), supporting the previously proposed close association between PBL, HIV and EBV infection. The mechanism by which EBV might be involved in the pathogenesis of PBL could be, as in EBV-associated HIV-positive lymphomas, the reactivation of latently EBV-infected B cells concomitant with deregulation of T cell immunosurveillance.

In the past few years the clinical spectrum of this disease has been expanded and PBL has also been documented in extraoral sites, such as the anorectum, nasal and paranasal regions, skin, testes, bones and lymph nodes.9 As far as we know, the present paediatric case is the first PBL reported with the vulva as the primary organ involved.

According to CT observations, a stage III was assigned. Castillo et al reported that 98% of patients with PBL have either stage I or IV disease.6

The patient was treated with cyclophosphamide, vincristine, metrotexate and doxorubicin, along with antiretroviral therapy. The patient received six cycles of chemotherapy, after which she showed an excellent response with substantial decrease in lesion size, with normal brain, thoracic and abdominal CT scans. Furthermore, she has currently achieved clinical remission, and is still free of disease after 15 months of follow-up.

Since first described, 112 cases of HIV-associated PBL have been reported worldwide, from 1 January 1997 to 31 December 2007,6 and only two of them have been described in children.10 11 In the current report we described a 3-year-old HIV-positive female paediatric case of PBL, stage III, with a previously undescribed localisation: the vulva. Further studies are needed in order to increase our understanding of the lymphomagenesis of PBL, together with the mechanism of the probable EBV-driven transformation of plasmablasts.

Take-home message

In this study, we present what is believed to be the third case of paediatric Epstein–Barr virus positive HIV-related plasmablastic lymphoma, and the first with a vulvar localisation.

Acknowledgments

PC and MVP are members of the National Research Council (CONICET), Research Career Programme and ML is a National Research Council (CONICET) doctoral fellow.

REFERENCES

Footnotes

  • Competing interests: None.

  • Funding: This study was supported in part by a grant from National Agency for Science and Technology Promotion (PICT 2005 no. 38217).

  • Ethics approval: Ethics approval was obtained from the ethics committee of Ricardo Gutierrez Children’s Hospital.

  • Patient consent: Parental consent obtained.