Maria Addesso

p53 over-expression identifies a subset of nodal peripheral T-cell lymphomas with a distinctive biological profile and poor clinical outcome.

Peripheral T‐cell lymphomas (PTCL) are usually characterized by aggressive clinical behaviour and poor clinical outcome, but their biological background has not been extensively investigated to date, due to their low incidence, about 10% of all non‐Hodgkins lymphoma cases in Western countries, and also to the paucity of specific molecular‐genetic abnormalities. Neverthless, there is increasing biological and clinical evidence that primary nodal PTCL should be considered separately from extra‐nodal cases, but little is known about biological factors of possible clinical and prognostic impact. This immunohistochemical study has analysed the expression of p53, Mdm2, p21WAF1, BCL‐2 and p‐glycoprotein (MDR‐1 gene product) in a series of 45 cases of nodal peripheral T‐cell lymphomas (PTCL) with ‘high‐grade’ histology. The immunohistochemical findings were then correlated with proliferative activity and clinical outcome. p53 was over‐expressed in 13 cases (28.9%). p53 positive cases showed significantly higher proliferative activity (p<0.01), more frequent expression of Bcl‐2 (p<0.01) and less frequent expression of p21WAF1 than p53 negative cases. Mdm2 and p‐glycoprotein were expressed in 4/13 (30.8%) and 8/13 (61.5%) p53 positive cases respectively, and in none (0%) of the p53 negative cases (p<0.01). Analysis of the survival curves showed that p53 positive cases were associated with a significantly poorer clinical outcome than p53 negative cases, in terms of both overall survival (p=0.0032) and event‐free survival (p=0.0004). Furthermore, multivariate analysis showed that p53 expression was the most important independent prognostic variable. These findings indicate that p53 over‐expression identifies a subset of nodal PTCL cases with a distinctive biological profile (higher proliferative activity, less frequent expression of p21WAF1 and more frequent expression of Bcl‐2, Mdm2 and p‐glycoprotein than p53 negative cases) and poor clinical outcome. The immunohistochemical analysis of p53 expression is a simple, rapid and low‐cost method which may provide information of potential clinical and prognostic value in nodal peripheral T‐cell lymphomas. Copyright

KSHV- and EBV-associated germinotropic lymphoproliferative disorder: a rare lymphoproliferative disease of HIV patient with plasmablastic morphology, indolent course and favourable response to therapy.

We describe a case of an unusual lymphoproliferative disease in a 60-year-old man. He presented at Hospital ‘‘Cardarelli’’ in March 2004 with fever, fatigue and weight loss. Physical examination and CT scan revealed a cervical lymphadenopaty, involving right laterocervical lymph node without enlargement of other lymph nodes. Laboratory serum tests for the common microrganisms and HIV were negative. A cervical lymph node biopsy was performed. Immediate post-operative follow-up with radiological studies and bilateral bone marrow biopsies did not reveal systemic involvement, nor evidence of monoclonal gammopathy found. No additional therapy was done. Later, the patient was dismissed for further evaluation. Today, after two years of diagnosis, there is no clinical evidence of relapse. For light microscopic examination, 4-mm-thick, formalin-fixed, paraffin-embedded tissue sections of case were stained with hematoxylin-eosin, periodic acid-Schiff and Giemsa. Consecutive sections were stained with antibodies to Ig heavy chains, light chains k, l, and CD10, CD20, CD19, CD22, CD21, CD30, CD79a, CD138, BCL2, BCL6, MUM1 and Ki67 (Dako, Glostrup, Denmark). For HHV-8 immunodetection was used in the monoclonal antibody for the latent nuclear antigen LNA-1 (clone 13B10, Cell Marque, Hot Springs, AR). Infection by EBV was investigated by in situ hybridization for EBV early RNA (EBER). For immunoglobulin gene rearrangements, we amplified DNA from whole paraffin sections of the CDRIII region of the rearranged IgVH gene using a mixture of seven framework 3 (FR3) family-specific primers and a consensus fluorescent primer for the JH gene. The surgical specimen consisted of a right cervical lymph node that measured 2.861.2 cm in diameter and had a fleshy cut surface. Histological examination showed the lymph node architecture partially effaced by a vaguely nodular infiltrate [Figure 1(a)] of atypical large cells resembling plasmablasts or immunoblasts, in small clusters or large sheets with involving the centre of lymphoid follicles [Figure 1(b)]. The ‘‘germinotropism’’ was confirmed by the presence of KSHV-positive cells within a meshwork of follicular dendritic cells CD21þ. Plasmablasts were also found in the mantle and interfollicular zones, often admixed with scattered individual large lymphoid cells and small aggregates of mature plasma cells [Figure 1(c)]. Residual atrophic lymphoid follicles were present. Immunohistochemical study showed that the plasmablasts were strongly positive for KSHV LNA-1 and co-expressed EBV as revealed by EBVencoded RNA (EBER) in situ hybridization

Improvement of interleukin 2 production, clonogenic capability and restoration of stromal cell function in human immunodeficiency virus-type-1 patients after highly active antiretroviral therapy.

Summary. Haematological abnormalities frequently occur in patients infected by human immunodeficiency virus‐type 1 (HIV‐1). Increasing evidence indicates that bone marrow suppression (BM) results from viral infection of accessory cells, with impaired stromal function and alteration of haematopoietic growth factor network. We have investigated the effects of antiretroviral therapy on cytokine and chemokine production by BM cells and stromal cells in a group of HIV‐1‐infected subjects before and during treatment. Compared with uninfected controls, an altered cytokine and chemokine production by BM cells was observed before treatment, characterized by decreased interleukin 2 (IL‐2) and elevated tumour necrosis factor‐α, macrophage inflammatory protein (MIP)‐1α, MIP‐1β, and RANTES (regulated on activation, normal T cell‐expressed and secreted) levels, along with a defective BM clonogenic activity. Antiretroviral therapy showed increased BM clonogenic capability, associated with normalization of IL‐2 production and chemokine receptors expression on CD34+ cells. Pre‐therapy, BM accessory cells were represented by macrophage‐like cells, in some cases positive for HIV‐1 DNA, suggesting that these cells are the main target of HIV‐1 infection. During therapy, the stromal cells became predominantly fibroblastoid‐like, as observed in normal controls, and were negative for HIV‐1 DNA. Controlling HIV‐1 replication may produce amelioration of stem cell activity, and restoration of stromal cell pattern and functions, with increased IL‐2 production at BM level.

Mucinous carcinoma of thyroid gland. Report of a primary and a metastatic mucinous tumour from ovarian adenocarcinoma with immunohistochemical study and review of literature

Mucinous carcinoma of the thyroid gland is an uncommon tumour that from the histological point of view, resembles mucinous carcinoma of others sites. Although a mucinous appearance has sometimes been reported in association with cases of typical thyroid carcinoma, true mucinous carcinoma is exceptionally rare. We describe two cases of thyroid tumours with mucinous differentiation studied with immunohistochemistry. Both cases disclosed a similar histological appearance, with small nests and sheets of malignant epithelial cells associated with extensive extracellular mucin that substituted and entrapped the follicular parenchyma of the thyroid. Thyroglobulin and focally thyroid transcription factor (TTF) 1 were positive in one case. From these findings, we classified this tumour as primary mucinous thyroid carcinoma. Thyroglobulin and TTF-1 were negative in tumour cells of second case; on the contrary, positivity to the carcinoembryonic antigen and CA-125 was strong and generalized. However, successfully, the patient presented ascites associated to right ovarian mass. In this case, thyroid tumour represents the first clinical sign of an ovarian mucinous adenocarcinoma, and it has not been previously described in literature. Both patients died after few months to diagnosis. In conclusion, primary and secondary mucinous carcinoma are rare and unusual tumours of the thyroid gland that can be a cause of pitfall in differential diagnosis. In these cases, for a correct diagnosis, a complete clinical history, restricted histological criteria and immunohistochemical panel are necessary.

A minute focus of extranodal marginal zone B-cell lymphoma arising in Hashimoto thyroiditis diagnosed with PCR after laser capture microdissection: a case report

BackgroundPrimary thyroid gland lymphomas are uncommon tumours that occur in the setting of lymphocytic thyroiditis or Hashimotos disease in almost all cases. In this condition a distinction between an inflammatory lymphoid infiltrate and a low grade lymphoma may be extremely difficult and precise criteria are necessary for a correct diagnosis.Patient and methodsWe report a case of a minute focus of primary extranodal marginal zone B-cell lymphoma (EMZBCL), incidentally discovered in a 63-year-old man with Hashimoto thyroiditis (HT) and diagnosed by means of polymerase chain reaction (PCR) after laser capture microdissection.The histological examination of surgical specimen confirmed the diagnosis of HT and showed a minute focus of dense lymphoid infiltrate (less than 4 mm in diameter), composed by centrocyte-like cells forming MALT balls. Immunoistochemistry was not useful. A microscopic focus of EMZBCL was suspected on the basis of morphological features. PCR assays revealed the rearrangement of the heavy chain of immunoglobulins only in the microdissected suspicious area, confirming the diagnosis of EMZBCL.ConclusionOur finding suggests that in cases of autoimmune thyroiditis a careful examination of the thyroid specimen is warranted, in order to disclose areas or small foci of lymphomatous transformation. Furthermore, in difficult cases with doubtful immunohistological findings, ancillary techniques, such as molecular studies, are necessary for a conclusive diagnosis.

Hepatoid carcinoma of the ovary with sex cord stromal tumor: a previously unrecognized association

BackgroundHepatoid carcinoma (HC) of ovary is a rare type of epithelial tumor composed mainly of epithelioid cells with abundant acidophilic cytoplasm, histologically indistinguishable from hepatocellular carcinoma. We report a previously unrecognized case of HC of ovary concurrent with a Sertoli cell tumor.Case reportA 42-year-old woman patient with a long-term history of hepatitis C presented with a mass of left ovary without evidence of hepatic tumor. After initial diagnosis of primary ovarian carcinoma (FIGO Stage I), she had experienced a first recurrence in upper abdomen. Histologically, the primary tumor was composed of epithelioid cells with “hepatoid features” in association with a sex cord stromal tumor of Sertoli-type. Immunohistochemistry hepatoid cells stained positively for hepatocyte paraffin-1, alpha-fetoprotein and alpha-1 antitrypsin; moreover, Sertoli-type cells were positive for alpha-inhibin, calretinin and CD99. A final diagnosis of HC concurrent with Sertoli-type tumor was made.ConclusionThe occurrence of this unreported association of HC with Sertoli-like tumor, the problems of differential diagnosis and therapeutic management of these tumors are the subject of this presentation. A diagnosis of ovarian metastasis from hepatocellular carcinoma is easy in patients with known primary tumor of liver and should be always excluded in these cases as an hepatoid variant of yolk sac tumor. Immunohistochemistry is not useful in these cases. However, a combination of clinical and pathological features is necessary for a correct diagnosis.

Nonpolypoid Intestinal Mantle Cell Lymphoma Resembling MALT Lymphoma with Successful Response to Rituximab

Two unusual cases of mantle cell lymphoma are reported. They involved the ileum and right colon without multiple lymphomatous polyposis and morphologically resembled an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.

Pleomorphic lipoma of the tongue as potential mimic of liposarcoma.

We herein report a rare case of pleomorphic lipoma of the tongue with a review of world literature. A 44-year-old woman presented with a nodule of the tongue that had been present for over three years. Clinical examination revealed a yellowish sub-mucosal lesion, measuring 3 cm in maximum diameter, protruding from lingual surface. A first biopsy showed a lipomatous tumour composed of mature adipocytes intermingled with myxoid areas composed of spindle uniform in size and shape and multinucleated floret-like giant cells. Spindle and giant cells were positive for CD34. A diagnosis of pleomorphic lipoma was made. In view of the benign nature of this mass, it was de-bulked rather than completely excised in order to preserve swallowing function.

B Cell Clonality in Multiple Localizations of Primary Central Nervous System Lymphomas in AIDS Patients

The aim of our study was to investigate B cell clonality of distinct localizations of primary central nervous system lymphomas (PCNSL) in AIDS patients. We selected seven autoptic cases of AIDS PCNSL with at least two separated localizations of the disease in the central nervous system (CNS). Clonality was investigated by immunoglobulin light chain restriction and by semi-nested PCR for the immunoglobulin heavy chain (IgH). Three cases showed a concordant restriction in the two lesions. In an additional case, an identical IgH sequence was found. The remaining three cases did not provide consistent information because of extensive necrosis in the lesions. Our findings suggest that multifocality of PCNSL is due to dissemination of a single neoplastic clone rather than to a synchronous transformation of multiple B cell clones.

The first case of benign multicystic mesothelioma presenting as a splenic mass

Multicystic mesothelioma (MM) is a relatively rare tumour arising in the pelvic peritoneum of the tuboovarian region of young woman. Exceptionally, MM occurs on the serosal surfaces of various organs including kidney, bladder, lymph nodes, and liver. We report here the first case of MM wherein a 58-year-old woman with a previous history of endometriosis of the right ovary presented with a large multicystic mass of the spleen. The diagnosis of MM was made on a surgical specimen after splenectomy. A histopathologic examination is always necessary for the diagnosis of MM which should be differentiated from other lesions particularly from cystic lymphangioma. At one year follow-up, the patient had no evidence of recurrence. Despite the high frequency of local recurrences, MM is a benign lesion and ‘en bloc’ surgical excision with prolonged follow-ups is the treatment of choice.