Athina Androulaki

Topoisomerase IIα Expression as an Independent Prognostic Factor in Hodgkin's Lymphoma

Purpose: To correlate the immunohistochemical expression of topoisomerase IIα (topoIIα) in Hodgkins lymphoma (HL) with clinicopathological parameters, the expression of Ki-67 and the outcome of patients, who had been homogenously treated with ABVD or equivalent regimens. Experimental Design: Immunohistochemistry using the monoclonal antibody Ki-S1 (topoIIα) was performed in 238 HL patients. MiB1 (Ki-67) expression was evaluated in 211/238. Results: The mean ± SD percentage of topoIIα- and Ki-67–positive Hodgkin-Reed-Sternberg (HRS) cells was 63 ± 19% (5%-98%) and 73 ± 19% (8%-99%), respectively. The median percentage of topoIIα-positive HRS cells was 64% (interquartile range, 51-78%). There was no correlation between topoIIα expression and patient characteristics. TopoIIα and Ki-67 expression were correlated (Spearmans Rho 0.255, P < 0.001). TopoIlα expression within the highest quartile of this patient population was predictive of failure free survival (FFS) (10-year rates 82 ± 3% vs 68 ± 7%, P = 0.02 for patients falling into the quartiles 1-3 and 4 respectively). In multivariate analysis topoIIα expression was independently predictive of FFS. Conclusion: TopoIIα was expressed in all cases of HL showing a correlation with Ki-67 expression. Under current standard therapy including drugs inhibiting its activity, topoIIα was an independent adverse predictor of FFS with no statistically significant correlation with other established prognostic factors.

Inflammatory pseudotumor associated with Mycobacterium tuberculosis infection

BACKGROUND Inflammatory pseudotumor is a relatively rare entity; originally identified in the lung, it has been described in multiple extrapulmonary anatomic locations. CASE REPORT We report on the unusual case of an inflammatory pseudotumor associated with Mycobacterium tuberculosis infection, which was initially mistaken for a renal malignancy both in clinical and radiological settings. We additionally present three brief reviews concerning: (1) infectious agents postulated to induce morphological changes of an inflammatory pseudotumor; (2) mycobacterial pseudotumors; and (3) distinction from inflammatory myofibroblastic tumors of the renal pelvis. CONCLUSIONS The present case highlights the diagnostic importance of PCR-based detection of mycobacterial DNA in granulomatous tissue responses. It is of crucial importance that clinicians are aware of this unusual manifestation of mycobacterial infection to ensure that pertinent laboratory evaluation is employed and appropriate treatment is administered in order to avoid potential clinical implications.

A morphometric study of bone marrow angiogenesis in hairy cell leukaemia with clinicopathological correlations

Summary. Bone marrow angiogenesis has recently been implicated in the pathophysiology and course of various haematological malignancies. Little is known, however, about the significance of this phenomenon in hairy cell leukaemia (HCL). We evaluated various morphometric characteristics of microvessels, highlighted by means of anti‐CD34 immunohistochemistry, in the bone marrow of 44 patients with typical HCL, before and after treatment with interferon‐α (IFN‐α). Overall, bone marrow from 103 HCL patients and 20 controls was examined. Microvessel density (MVD) and several size‐ and shape‐related parameters were quantified in the region of most intense vascularization using image analysis. MVD, size‐related parameters and the percentage of branching microvessels were higher in HCL than in controls. Likewise, perimeter counts were higher in partial/non‐responders than in complete responders. Achievement of complete response was accompanied by smaller calibre microvessels. IFN‐α induced a decrease in MVD and branching values in cases with diffuse marrow involvement. In univariate analysis, progression‐free survival was adversely affected by MVD, branching and major axis length. Multivariate analysis indicated that MVD/branching independently affected progression‐free survival and the likelihood of complete response. Our data suggest that the generation of bone marrow microvessels indicated an increased risk of progression and IFN‐α treatment failure in HCL. Furthermore, the prognostic significance of angiogenesis requires the concomitant assessment of MVD and the complexity of the microvascular network.

Early-Stage Gastric MALT Lymphoma: Is It a Truly Localized Disease?

Early-stage gastric mucosa-associated lymphoid tissue lymphoma (GML) is considered a localized disease with an indolent course. Circulating malignant cells have been detected in other early-stage indolent lymphomas by molecular methods. We investigated the incidence of occult blood disease in early-stage GML patients, its impact on clinical outcome, and the similarity between blood and gastric lymphocytic clones. Sixty-two patients with localized GML were included in the study; 51 of them had Helicobacter pylori infection. Monoclonality was investigated by leader polymerase chain reaction. Sequencing was performed for the immunoglobulin variable gene (VH) analysis. Blood involvement was absent in all patients by conventional staging methods. In the whole group of 62 patients, the incidence of blood IgH rearrangement was 45%, and this did not correlate with baseline patient characteristics. The monoclonal blood and gastric products of five patients were sequenced and compared with each other. Clonal identity was evident in four of five patients. The VH3 gene was the most frequently used, both in the blood and in the stomach. Early-stage GML is not a truly localized disease because half the patients had a circulating clone, probably identical to the gastric one. The clinical significance of occult blood disease and the potential appropriate intervention need to be further investigated.

T cell lymphoblastic lymphoma in parotidectomy for Warthin’s tumor: case report and review of the literature

Lymphomas associated with Warthin’s tumor (WT) are extremely uncommon and the majorities are of B cell type. We report the simultaneous occurrence of T-cell lymphoblastic lymphoma (T-LBL) and WT in an 81-year-old patient, who presented with fever, night sweats and enlargement of the right parotid gland. The parotidectomy specimen showed a WT with extensive replacement of the lymphoid stroma by T-LBL, but preservation of the oncocytic epithelium. Staging investigations revealed mediastinal and abdominal lymphadenopathy, bilateral pleural effusions and bone marrow infiltration, in keeping with stage IVB disease. The patient received combination chemotherapy treatment but responded poorly, and died three months after diagnosis. To our knowledge, this is the first case report of T-LBL involving WT. The present study indicates that the lymphoid stroma in WT belongs to the systemic lymphoid tissue and can be involved in disseminated lymphoma. It highlights the importance of careful examination of WT’s lymphoid stroma for the possible presence of any coexistent malignancy.

Metastatic low-grade endometrial stromal sarcoma of clitoris: report of a case.

Low-grade endometrial stromal sarcoma (ESS) is an uncommon neoplasm, which has a highly recurrent nature. A review of the literature revealed that only one case of low-grade ESS, arising within the vulva from a focus of endometriosis, has been previously published. We describe an additional case of low-grade ESS arising within the vulva and to the best of our knowledge the first report of low-grade ESS metastasized to clitoris. A 46-year-old woman was admitted to our hospital due to a heavy uterine bleeding. A physical examination revealed a lesion in clitoris, which exhibited a densely cellular mesenchymal neoplasm on microscopy. On the basis of the pathologic features alone, a differential diagnosis of a low-grade ESS and cellular leiomyoma was considered. Seven months later, the patient presented again with excessive uterine bleeding and a total hysterectomy was performed. A tumor of white-tan, whorled appearance was found. Its features were suggestive of low-grade ESS. Taking into account the possible extrauterine location of an ESS and reviewing the first case, a diagnosis of rare low-grade ESS metastasized to clitoris was made

Localized Castleman’s disease associated with systemic AA amyloidosis. Regression of amyloid deposits after tumor removal

Dear Editor, We are writing to report a case of a 49-year-old woman who was referred to our hospital due to malaise, fatigue, and profound chronic hypochromic microcytic anemia. She had a 5-year medical history of intermittent low-grade fevers and chronic anemia of unknown etiology, which was unresponsive to iron therapy. She had no history of hypertension, diabetes, smoking, or alcohol abuse. Physical examination revealed pale skin and conjunctivae, hepatomegaly 4 cm below the costal margin and mild splenomegaly. No peripheral lymphadenopathy was present. Bilateral xanthelasma of the eyelids was noted. Laboratory examination revealed normochromic microcytic anemia (Hct 21.3%, Hb 6.7 mg/dl, MCV 73 fl), elevated erythrocyte sedimentation rate (155 mm in 1 h) and CRP (126 mg/dl), thrombocytosis (PLT 886,000/μl) and polyclonal hyperglobulinemia. Renal function tests were within normal range. Results of the laboratory findings were as follows: urea 102 mg/dl, creatinine 2.6 mg/dl, Na 133 mEq/l, K 4.2 mEq/l, Ca 4.4 mEq/l, amylase 181 U/l, uric acid 6.35 mg/dl, total cholesterol 125 mg/dl, LDL 99 mg/dl, cholerythrin 0.49 mg/dl, ALP 854 U/l, γGT 85 U/L, sGOT 14 U/L, SGPT 12 U/L, total protein 10.4 g/dl, albumin 3.6 g/dl, LDH 199 U/l, CPK 20 U/L. Serologic tests for Epstein–Barr virus, cytomegalovirus, human herpes virus 8, hepatitis B virus, hepatitis C virus, and HIV were negative. A CT scan of the abdomen and pelvis with IV contrast revealed a retroperitoneal mass in the lower pelvis measuring 7.8 cm in diameter, mild hepatomegaly, and splenomegaly. The patient underwent surgical resection of the mass. A transcutaneous liver biopsy was also performed. Grossly, the mass was well-circumscribed, solid, with a variegated yellowish, brown, and gray cut surface. On microscopic examination, a lymph node structure was evident with numerous lymphoid follicles, some of which showed vascular structures in their germinal centers and a prominent hyaline-like change (Fig. 1a). In the interfollicular and parafollicular areas, numerous polyclonal plasma cells were present, which associated with massive deposits of eosinophilic material (Fig. 1b). Similar deposits were found into the surrounding fat tissue and blood vessels. These deposits showed green birefringence with Congo red stain under polarized light, and they were immunohistochemically (anti-human amyloid A, clone mc1, Dako, Glostrup, Denmark) proven to consist of AA amyloid (Fig. 1c). The liver biopsy specimen showed massive AA amyloid deposits in the liver sinusoids and portal tracts (Fig. 1d). After tumor resection, a rapid resolution of clinical symptoms and acute phase reactants was noticed. On 2 years follow-up, the patient’s general condition was considerably improved, with regression of amyloid deposits —as determined by abdominal fat aspiration biopsy — while the hemoglobin was stable to normal values. Castleman’s disease (CD), described in 1956 as giant lymphoid hyperplasia, is a heterogeneous entity related to Ann Hematol (2007) 86:55–57 DOI 10.1007/s00277-006-0187-0

Maltoma of the Thyroid and Sjögren's Syndrome in a Woman with Hashimoto's Thyroiditis

We report the case of a 70-yr-old woman with maltoma of the thyroid, Sjögren’s syndrome, and a history of Hashimoto’s thyroiditis. The patient underwent a total thyroidectomy for a recently growing mass of the thyroid, while being treated with l-thyroxine for Hashimoto’s thyroiditis. Postoperatively, routine histologic examination was consistent with the diagnosis of chronic lymphocytic thyroiditis of autoimmune etiology. Three years later, the patient presented with high temperature, anorexia, and coughing. This time, a microscopic examination of deeper thyroid tissue sections and an immunohistochemical study revealed a low-grade, non-Hodgkin lymphoma, MALT type. Simultaneously, the diagnosis of Sjögren’s syndrome was established and the patient is currently under investigation for generalized lymphoma. This case clearly demonstrates the difficulty in differentially diagnosing Hashimoto’s thyroiditis from low-grade MALT lymphoma by the use of routine histologic examination.

Pure red cell aplasia associated with true thymic hyperplasia

Pure red cell aplasia was diagnosed in a 35-year-old otherwise healthy woman. Chest computed tomography (CT)-imaging investigation, detected an upper mediastinal mass corresponding to the thymus gland. A thoracotomy was performed and an enlarged thymus mass was removed, rapidly followed by a full hematologic recovery. Thymic histology confirmed a significant degree of hyperplasia. We conclude that not only thymomas but also other types of thymic pathology may be associated with this type of hematologic dyscrasia.

Increased angiogenesis in the bone marrow of HIV-positive patients with myelodysplasia

Aim: Little is known about the significance of angiogenesis in the bone marrow of HIV‐positive patients with myelodysplastic features (MDF). However, this process has been associated with the pathogenesis of primary myelodysplastic syndromes (MDS). The aim of the study was to investigate angiogenesis in the bone marrow of HIV‐positive patients. Methods: Bone marrow biopsies from 28 HIV‐positive patients were immunostained for factor VIII and the microvessel density (MVD) was quantitatively evaluated and compared with that of 32 biopsies from patients with primary MDS and to 18 control bone marrows from patients with no evidence of bone marrow disease. Results: Bone marrow MVD in HIV‐positive patients was similar to that of MDS. However, both groups revealed significantly higher MVD counts compared to those of control bone marrows (MDF vs controls P=0.022, MDS vs controls P=0.001). Conclusions: Bone marrow from HIV‐positive patients with MDF reveals similar microvessel counts compared to those with primary MDS, although both differ significantly from that of control bone marrow. Elucidation of the mechanisms underlying bone marrow angiogenesis in HIV‐positive patients, may provide further insights into the pathobiology of AIDS and might be of value for the development of new therapeutic strategies for this disease.