Amedeo Boscaino

Intraepithelial carcinoma arising in an endodermal cyst of the posterior fossa

Endodermal cysts of the central neuraxis are benign, non‐neoplastic epithelium‐lined cysts arising from endodermal tissue that have been displaced early in fetal life. Intracranial endodermal cysts are rare and usually located in the posterior fossa. The present study involves a 36‐year‐old man with a typical epithelial cyst in the posterior fossa. Microscopically, the cyst has a simple columnar epithelium with mucus‐producing cells, containing an area composed of dysplastic epithelium with evidence of an intraepithelial carcinoma. The atypical cells have a high proliferative fraction demonstrated by Ki‐67 immunostain. Based on these findings, the authors view this case as evidence of a malignant transformation of a classic endodermal cyst. The clinicopathologic features and a review of the literature are discussed.

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

Primary peripheral PNET/Ewing's sarcoma of the dura with FISH analysis

deposits including C1q were found. Electron microscopy confirmed a moderate amount of electron-dense deposits in the mesangial and paramesangial regions (Figure 3). A diagnosis of IgA nephropathy with prominent crescent formation was made. With respect to the biopsy findings, the patient was put on intravenous methylprednisolone (500 mg for 3 days) and cyclophosphamide (50 mg daily) immunosuppressive therapy. There was no improvement in renal function and he died of septicaemia after 1 month. Autopsy was not performed. Nephrotic syndrome due to membranous glomerulonephritis has been well documented as one of the rare clinical manifestations of chronic GVHD. To the best of our knowledge only six cases of clinically significant GVHD-associated renal damage other than membranous nephropathy have been recorded in the English literature (Table 1). All these patients presented with heavy proteinuria ⁄ nephrotic syndrome. Minimal change disease, diagnosed in four of these patients, was the commonest form of glomerular injury. The pathogenesis of glomerular lesions after BMT is not well understood. It is generally believed that an immune complex-mediated mechanism during the course of GVHD may play a key role. Glomerular permeability might be altered by cytokines secreted by donor T lymphocytes in GVHD, thus accounting for the heavy proteinuria. IgA nephropathy was recognized in the setting of GVHD after BMT only recently. Mesangial deposition of Haemophilus parainfluenza outer membrane (OMHP) antigen and decrease in glycosylation of the IgA1 hinge have been implicated in the pathogenesis of IgA nephropathy. Such mechanisms have also been implicated in the aetiology of GVHD-associated IgA nephropathy after BMT. Recipient lymphocytes derived from donor haematopoietic stem cells may produce IgA-type antibody against OMHP antigen. The IgA might be damaged by infection or immunosuppressive therapy after BMT, become underglycosylated and deposited in the glomeruli. Though our patient had chronic HCV infection which has also been reported to be associated with IgA nephropathy, the relationship between HCV and IgA nephropathy is much debated and questionable. IgA nephropathy can complicate the course of GVHD after BMT. The clinical course of both Kimura et al’s and our case suggest an exacerbation associated with BMT and GVHD. IgA nephropathy should be entered into the differential diagnosis in patients who develop heavy proteinuria after BMT. G S-W Chan M F Lam W Y Au K C Tse T M Chan K N Lai K W Chan

Monotypic epithelioid angiomyolipoma of the adrenal gland: an unusual site for a rare extrarenal tumor.

Epithelioid angiomyolipoma (AML) is an uncommon renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis. Extrarenal AMLs are rare, and to the best of our knowledge, this is the first reported case of a primary monotypic epithelioid AML of adrenal gland in a patient without evidence of tuberous sclerosis. The patient is a 42-year old man who presented with retroperitoneal hemorrhage resulting from spontaneous rupture of adrenal mass. Histologically, the tumor showed a prominent component of epithelioid smooth muscle cells with slightly pleomorphic nuclei, sometimes with prominent nucleoli and eosinophilic cytoplasm resembling oncocytic tumors. Epithelioid cells were positive for melanoma (HMB45 and positive MelanA) and smooth muscle markers (alpha-smooth muscle-specific actin), but not for epithelial markers (cytokeratin, EMA). Differential diagnosis from renal cell carcinoma, adrenal gland carcinoma, and metastatic carcinoma is often challenging because of its epithelioid morphology. Because primary and secondary malignant tumors are much more common and aggressive neoplasms, establishing the correct diagnosis has important therapeutic and prognostic implications.

Lymph node-based disease and HHV-8/KSHV infection in HIV seronegative patients: report of three new cases of a heterogeneous group of diseases

We describe three cases of lymph proliferative diseases characterized by the presence of lymphoma cells expressing the KSHV/HHV-8 antigen with or without EBV expression. The patients were HIV seronegative without serous effusions. One case was diagnosed as KSHV-germinotropic lymphoproliferative disorder due to the presence of atypical plasmablasts involving germinal centers. These plasmablasts were positive for MUM1 and vIL6, co-expressed EBV and LNA-1of HHV-8/KSHV, and showed a polyclonal pattern of Ig gene rearrangements on PCR. The disease was localized and the prognosis was good. In two other cases, a diagnosis of KSHV/HHV-8-related diffuse large cell B-lymphoma morphology was made. The lymphoma cells were anaplastic or frankly pleomorphic, expressed KSHV but not EBV, and were positive for CD20, MUM1, PAX-5, and vIL6. In both cases the prognosis was poor. On the basis of the features observed, we raise three considerations: (1) KSHV-related lymphoproliferative disorders represent a distinctive and heterogeneous group of diseases with variable clinico-pathologic findings and immunophenotypes (BCL6−/MUM1+/CD138− and BCL6+/MUM1+/CD138− or BCL6−/MUM1+/CD138+). (2) Although the pathogenic mechanism of HHV8 in lymphomagenesis is unclear, the presence the viral DNA in lymph nodes of HIV− patients is not a simply opportunistic infection, but is directly implicated in the pathogenesis of KSHV-related diseases; the activation of IL-6 receptor signalling may play an important role in most cases. (3) The different prognoses among different diseases with KSHV etiology may be related to the fact that the pathogenic potential appears to be constrained by a competent immune system.

Concurrence of marginal zone B-cell lymphoma MALT-type and Langerhans cell histiocytosis in a thyroid gland with Hashimoto disease

Dear Editor, A 55-year-old woman presented with a clinical history of hypothyroidism and goiter with secondary obstructive symptoms, including dysphagia and stridor. On physical examination, the thyroid gland was diffusely enlarged, firm, with no pain on palpation, and no lymphadenopathy. The ultrasound study revealed a diffuse enlargement of the gland with no detectable calcifications. Laboratory tests were indicative of the Hashimoto’s thyroiditis (HT). A fine needle aspiration revealed atypical follicular cells. The patient underwent an elective thyroidectomy. The thyroid gland was found to be diffusely enlarged with a firm, vaguely nodular, gray-yellowish cut surface in both lobes (Fig. 1a). The histological examination showed microscopic findings indicative of HT: broad bands of collagen separated lobules of thyroid tissue, which was heavily infiltrated by small lymphocytes, plasma cells, and lymphoid follicles with large germinal centers. The thyroid follicles were atrophic with an extensive oncocytic cell metaplasia. In the setting of HT, we observed the areas of diffuse effacement of the thyroid tissue with an extensive destructive lymphoid infiltrate. At low magnification, the lymphoid population showed paler areas alternating with darker areas for the presence of small lymphocytes with slightly irregularly folded nuclei (centrocyte-like), plasma cells, and monocytoid cells. Colonization of germinal centers and scattered atypical large lymphoid cells were also present. Groups of entrapped, markedly reactive follicular cells were seen within the lymphoid aggregates. Moreover, centrocyte-like lymphoid cells displayed the tendency to invade and expand the lumen of thyroid follicles, as seen in mucosa-associated lymphoid tissue (MALT)-balls (Fig. 1b). Small areas composed exclusively by large cells with a moderate amount of pale eosinophilic cytoplasm and oval or reniform nuclei with indentations and grooves, resembling Langerhans cells (LC), were closely associated with the lymphoid infiltrate (Fig. 1c). Sparse eosinophil granulocytes were present among these cells. The lymphoid cells showed the following immunophenotype: CD20+, CD43+ (Fig. 1d), CD5−, CD10−, bcl6−, and cyclinD1−. Germinal center B-cells were bcl2−. The large cells with the morphological features of LC were positive for S100 protein and CD1a (Fig. 1e). The lesion appeared confined within the glandular parenchyma with no extrathyroid extension. A diagnosis of marginal zone Bcell lymphoma (MZBCL) MALT-type arising in the setting of HT with associated Langerhans cell histiocytosis (LCH) was made. We evaluated the expression of bcl10 in MALT lymphoma. The immunohistochemical staining showed an aberrant expression in both nucleus and cytoplasm of lymphoma cells (Fig. 1f). Radiological exams excluded an extrathyroid localization of the lymphoproliferative disease. The patient subsequently underwent radiation therapy and is still symptom-free 3 months after surgery. Ann Hematol (2008) 87:855–857 DOI 10.1007/s00277-008-0489-5

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.

Multicystic Mesothelioma of the Liver with Secondary Involvement of Peritoneum and Inguinal Region

A case of multicystic mesothelioma of the liver with secondary involvement of the pelvic peritoneum and the inguinal region is presented. The case is of interest because of its unusual location and peculiar biological behavior.

CD90 Expression in Atypical Meningiomas and Meningioma Metastasis

OBJECTIVES Meningiomas are slow-growing intracranial/intraspinal tumors, with a wide range of histopathologic variants. The more aggressive atypical and malignant types can disseminate via the venous system, lymphatic, system, or cerebrospinal fluid, with the lung and pleura being the most common sites of extracranial metastases. A case of metastatic meningioma with high expression of CD90 was spotted during a review of flow cytometry data for lung malignancies. Therefore, we have analyzed CD90 expression in a series of meningioma metastases with their corresponding primary tumors and in a series of 92 primary meningioma tumors. METHODS In addition to flow cytometry and immunohistochemical analysis of the case, a series of meningiomas and relative metastases has been evaluated for CD90 immunohistochemical expression. Furthermore, an immunohistochemical analysis has been conducted in a tissue microarray, including typical and atypical meningiomas. RESULTS CD90 had high expression in three of four cases of metastases and in their corresponding primary atypical meningioma. In addition, CD90 was significantly expressed in atypical rather than in typical meningiomas (P = .003). However, the correlation of CD90 with patient survival reveals only a trend of statistical association with extracranial metastases. CONCLUSIONS CD90 is a biomarker overexpressed in atypical meningioma, with a potential role in metastatic switch of this tumor.

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.