Concurrent presentation of nodal myeloid sarcoma and bone marrow chronic lymphocytic leukemia/small lymphocytic lymphoma: a unique association.

Myeloid sarcoma (MS), previously known as granulocytic sarcoma, is a rare, localized, tumor mass composed of myeloid precursor cells, with or without maturation, and occurring at an anatomical site other than the bone marrow (BM). Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), in contrast, is a B-cell hematological malignancy. We describe the first reported case of concurrent presentation of nodal MS and of BM CLL/SLL in the same patient. Fatal leukemic central nervous system infiltration was the final outcome. We provide possible explanations and investigate the pathophysiology of this unique, previously unreported co-morbidity.

Synchronous BALT Lymphoma and Squamous Cell Carcinoma of the Lung: Coincidence or Linkage?

A 72-year-old man presented with weight loss, fever, and malaise. Chest radiograph and CT revealed two large ill-defined masses in middle and left lower lobes. CT-guided biopsy of left lower lobe mass disclosed bronchus-associated lymphoid tissue (BALT) lymphoma. Middle lobe mass was considered second deposit in contralateral lung. The patient received chemotherapy for BALT. Followup CT disclosed regression of left lower lobe mass and stability of middle-lobe mass and of right paratracheal lymph nodes. CT-guided biopsy of middle-lobe mass revealed squamous cell lung carcinoma. Surgical biopsy of right paratracheal lymph nodes revealed malignancy. Disease was staged T3, N2, and M0. Combined chemotherapy for lung cancer and BALT lymphoma was initiated.

European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis.

BACKGROUND: The World Health Organization classification of myeloproliferative neoplasms discriminates between essential thrombocythemia and the prefibrotic phase of primary myelofibrosis. This discrimination is clinically relevant because essential thrombocythemia is associated with a favorable prognosis whereas patients with primary myelofibrosis have a higher risk of progression to myelofibrosis or blast crisis. DESIGN AND METHODS: To assess the reproducibility of the classification, six hematopathologists from five European countries re-classified 102 non-fibrotic bone marrow trephines, obtained because of sustained thrombocytosis. RESULTS: Consensus on histological classification defined as at least four identical diagnoses occurred for 63% of the samples. Inter-observer agreement showed low to moderate kappa values (0.28 to 0.57, average 0.41). The percentage of unclassifiable myeloproliferative neoplasms rose from 2% to 23% when minor criteria for primary myelofibrosis were taken into account. In contrast, the frequency of primary myelofibrosis dropped from 23% to 7%, indicating that the majority of patients with a histological diagnosis of primary myelofibrosis did not fulfill the complete criteria for this disease. Thus, over 50% of cases in this series either could not be reproducibly classified or fell into the category of unclassifiable myeloproliferative neoplasms. CONCLUSIONS: World Health Organization criteria for discrimination of essential thrombocythemia from prefibrotic primary myelofibrosis are poorly to only moderately reproducible and lead to a higher proportion of non-classifiable myeloproliferative neoplasms than histology alone.

Acute appendicitis secondary to Enterobius vermicularis infection in a middle-aged man: a case report.

INTRODUCTION: Acute appendicitis due to Enterobius vermicularis is very rare, affecting mostly children. Whether pinworms cause inflammation of the appendix or just appendiceal colic has been a matter of controversy. CASE PRESENTATION: A Caucasian 52-year-old man was referred to our Emergency Department with acute abdominal pain in his right lower quadrant. The physical and laboratory examination revealed right iliac fossa tenderness and leukocytosis with neutrophilia. An open appendectomy was performed. The pathological examination showed the lumen containing pinworms. Two oral doses of mebendazole were administered postoperatively. The follow-up to date was without incident and he was free of symptoms one year after the operation. CONCLUSION: The finding of E. vermicularis in appendectomy pathological specimens is infrequent. Parasitic infections rarely cause acute appendicitis, especially in adults.One should keep in mind that the clinical signs of intestinal parasite infection may mimic acute appendicitis, although rare. A careful evaluation of symptoms such as pruritus ani, or eosinophilia on laboratory examination, could prevent unnecessary appendectomies.

Aberrant CCND1 copies and cyclin D1 mRNA expression do not result in the production of functional cyclin D1 protein in anaplastic large cell lymphoma.

Scattered reports in the literature have shown that Cyclin D1 mRNA and protein may be expressed in anaplastic large cell lymphoma (ALCL). ALCLs are characterized by the presence of ALK translocations. Aberrant Cyclin D1 expression seems to promote proliferation in other types of lymphoma, while a growth promoting CCND1/TACSD1(TROP2) fusion product has also been described in tumors. Herein, we investigated 44 ALCL cases for chromosome 11 and CCND1 status (by FISH), cyclin D1 mRNA expression (by in situ hybridization and RT-PCR) and Cyclin D1 protein (by immunohistochemistry with two different monoclonal antibodies), as well as for the expression of Trop-2/GA733-1 (by immunohistochemistry). Polysomy of CCND1 (11q13) and chromosome 11 was found in 15/38 evaluated cases (39.5%). This change was specific for CD30+ neoplastic cells, as shown by double fluorescent staining. Neoplastic cells in the majority of ALCL expressed cyclin D1 mRNA (29/41 [70.7%]), in association with the presence of ALK translocations (p=0.024) and systemic, rather than cutaneous disease (p=0.021). Remarkably, however, Cyclin D1 protein was not detected in neoplastic cells (0/44 cases), neither were these found positive for Trop-2. In conclusion, aberrant copies of CCND1 / chromosome 11 may be observed in ALCL, probably as a consequence of the reported ploidy changes in these tumors. ALCL may often express cyclin D1 mRNA, which, however, does not result in the production of functional Cyclin D1 protein or Trop-2, suggesting that these proteins do not play a role in the pathogenesis of ALCL.

Successful treatment of extramedullary gastric plasmacytoma with the combination of bortezomib and dexamethasone: first reported case.

We report a case of a 68-year-old man presented with upper-gastrointestinal bleeding. Endoscopy showed a large ulcerated gastric mass. Histological examination of the gastric biopsies revealed a k monoclonal extramedullary plasmacytoma (EMP). Further staging was negative for multiple myeloma. The patient was managed with bortezomib at a dose of 1.3mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle in combination with dexamethasone 20mg p.o. on days 1, 2, 4, 5, 8, 9 and 11, 12 of each cycle. After 4 cycles of treatment, no endoscopic or histological findings of EMP were found. Thirteen months after diagnosis the patient is in complete remission with no evidence of local relapse or evolution to multiple myeloma. This is the first reported case of EMP successfully managed with the combination of bortezomib and dexamethasone.

Bortezomib is an effective agent for MDS/MPD syndrome with 5q- anomaly and thrombocytosis.

Thrombocytosis is not a frequent event in myelodysplasia (MDS) and is observed mainly in 5q- syndrome and MDS/myeloproliferative (MPD) overlap syndromes. The pathogenetic mechanism of thrombocytosis in 5q- has not been fully elucidated to-date. Bortezomib is a proteasome inhibitor which seems to be effective in MDS. We present here the first case in the literature with MDS/MPD syndrome, sole 5q- anomaly and thrombocytosis in which bortezomib administration normalized platelet count, produced a major erythroid response, and reduced levels of interleukin-6 (IL-6) and TNF-alpha while increased levels of IL-4 in the bone marrow plasma. The study of such cases will reveal the exact role of bortezomib in the management of MDS/MPD.

Primary gastrointestinal non-Hodgkin's lymphoma: a clinicopathologic study of 128 cases in Greece. A Hellenic Cooperative Oncology Group study (HeCOG).

The aim of this retrospective study was to illustrate the clinicopathologic data and the treatment results in patients with primary gastrointestinal tract non-Hodgkin's lymphoma (GI NHL). Among 810 patients with NHL, 128 cases (15.8%) were diagnosed as primary GI tract NHL. There were 79 males and 49 females with median age of 62 years. The most common primary site was the stomach (68%). Overall, 67.2% of the patients were in stages I - II, and 32.8% in stages III - IV. Simultaneous involvement of the GI tract and other extranodal sites was observed in 26 patients (20%). Extranodal marginal zone B-cell lymphoma (MZBL) (i.e., low-grade lymphoma of mucosa-associated lymphoid tissue type) accounted for 48.4% of lymphomas. Aggressive lymphomas (diffuse large B-cell lymphoma [DLBL]) accounted for 44.5%. Eighty-three patients (67.5%) achieved complete response (CR), either by surgery (43/43 patients, 17 with DLBL and 25 with MZBL) or by primary chemotherapy (40/64 patients, 22 with DLBL and 17 with MZBL). Sixty-two patients remain in CR; 33/43 after surgical resection (13/17 with DLBL and 20/25 patients with MZBL), and 29/40 after only chemotherapy (18/22 with DLBL and 10/17 with MZBL). The major prognostic factor for outcome in the present study was the stage of the disease. Patients with localized lymphoma (stage I and II) had significantly longer DFS and OS (DFS and OS at 3-year: 83% and 87%, respectively) than patients with extended disease (stage III and IV) (DFS and OS at 3-year: 46% and 60%, respectively) (P < 0.0001). The International Prognostic Index (IPI) for patients with aggressive lymphomas was prognostic only for DFS (79% for low-risk patients [IPI score 0 - 1] vs 49% for higher risk groups [IPI score >1] at 3-year, P = 0.0131).

In situ detection of hTERT variants in anaplastic large cell lymphoma.

The expression of hTERT and its isoforms is difficult to assess in lymphoma tissues with the commonly used reverse transcription-polymerase chain reaction (RT-PCR) methods, because non-neoplastic lymphocytes expressing hTERT are always present in the lymphomatous infiltrates. The present study aimed to investigate hTERT mRNA variants in anaplastic large cell lymphoma (ALCL) (n = 38) with in situ hybridization (ISH), along with the immunodetection of hTERT protein. Probes for the identification of mRNAs containing (Bplus) and lacking (Bdel) exons 7 and 8 of the hTERT mRNA were used. Normal lymphocyte populations equally expressed both Bplus and Bdel mRNAs. Although all ALCL examined were found positive for hTERT expression with RT-PCR, hTERT mRNAs were identified in 68% of these tumors with ISH, with a higher incidence in the group bearing ALK translocations (10 out of 11; 90.9%) compared to the ALK negative group (17 out of 27; 59.3%) (PPearson's = 0.002). The same results were obtained with immunohistochemistry for hTERT. In approximately 50% of cases, only Bplus positive cells were identified, again with a higher incidence in the ALK positive compared to the ALK negative group (PPearson's = 0.016). In conclusion, ISH for hTERT mRNAs appears to be a valuable tool for the investigation of hTERT expression in lymphomas. Aberrations in hTERT variant profiles and a decline in the expression of the B deleted isoform may be associated with the pathogenesis of ALCL, especially with respect to ALK positive tumors.

Multifocal extranodal non-hodgkin lymphoma: a clinicopathologic study of 37 cases in Greece, a Hellenic Cooperative Oncology Group study.

The purpose of this retrospective study was to illustrate the clinicopathological features of patients presenting with multifocal extranodal non-Hodgkin lymphoma (NHL). Among 810 patients with NHL, 37 cases (4.2%) were found to have multiple extranodal involvement (two or more sites). There were 24 men and 13 women, with a median age of 63 years. The majority of these cases (n = 26) had gastric or intestinal (GI) involvement with or without other extranodal sites. Lung along with another extranodal site was relatively common in the present series. Stratification of the 37 cases according to the International Prognostic Index (IPI) showed that 89% of the patients belonged to the high-risk groups. Diffuse large-B-cell lymphoma (DLBCL) accounted for 62%, and mucosa-associated lymphoma tissue (MALT) lymphoma accounted for 27% of all cases. After induction treatment with anthracycline-based regimens, complete remission was achieved in 21 patients (57%), partial remission was achieved in six patients (16%), and seven patients (19%) had no response, while three patients (8%) were nonevaluable. In conclusion, multifocal extranodal NHL is a heterogeneous group of diseases. The majority of them arise at various sites in the GI tract. DLBCL was the most frequent histological subtype followed by MALT lymphoma. Risk group, as defined by the IPI, was predictive of survival.

Occurrence of a variant Philadelphia translocation, t(10;22), in de novo acute megakaryoblastic leukemia.

Acute megakaryoblastic leukemia (AMegL) in adults is a very rare subtype of acute myeloid leukemia (AML) and is characterized by a larger diversity of chromosomal abnormalities than the other subtypes, including 3q21q26 changes, aberrations of chromosomes 5 and 7, and the t(9;22)(q34;q11). We report the case of a 24-year-old patient with de novo AMegL and thrombocythemic cell count. Diagnosis was established with a bone marrow biopsy, and cytogenetics with G-banding revealed a t(10;22), which by FISH, was found to be a variant Philadelphia translocation involving chromosome 10q in all 20 metaphases analyzed. We believe that this is the first report of de novo AMegL with this chromosomal abnormality, and its possible correlation with morphology and thrombocytosis is discussed.

An extremely rare case of synchronous occurrence in the larynx of intravascular lymphoma and in situ squamous cell carcinoma.

We present the first case of laryngeal intravascular lymphoma coexisting with in situ squamous cell carcinoma. The patient, a 53 years old man, presented with hoarseness starting a year ago and underwent laryngoscopy, which revealed two nodular lesions on his right vocal cord. The histological and immunohistochemical examination of the biopsy specimens established the diagnosis of in situ squamous cell carcinoma coexisting with intravascular lymphoma of T-cell origin. Taking in consideration all the available references, the larynx has not until now been reported as a primary site of involvement of intravascular (angiotropic) lymphomas, nor as a secondary location in the systematic course of this disease. Furthermore no cases have been reported in the literature, concerning the synchronous affection of the larynx by this lymphoma and in situ laryngeal carcinoma, or other type of neoplasm.

Mismatch repair gene expression in malignant lymphoproliferative disorders of B-cell origin.

We investigated mismatch repair (MMR) gene expression in 31 lymphoid tissue specimens and bone marrow aspirates with malignant lymphoproliferative disorders of B-cell origin (25 cases of lymphoma and six cases of plasma cell myeloma). A multiplex RT-PCR assay was employed to assess the relative expression of the hMSH2, hMLH1 and hPMS1 genes, as compared to beta-actin, which was used as an internal control of gene expression. MSH2 was further evaluated at the protein level by immunohistochemistry. The findings were compared to those of a control group of lymphoid tissue specimens without evidence of malignancy (n = 6). Changes in MMR gene expression were observed in 10 out of 31 cases of the study group (32%). All three MMR gene transcripts were low in two out of six plasma cell myelomas, which had extensive bone marrow infiltration by neoplastic cells. The hMSH2 transcript was present in all cases of lymphoma, while the expression of hMLH1 and hPMS1 was significantly low in some large B-cell lymphomas (four and five out of 14 cases, respectively) and in mantle cell lymphomas of the blastoid type (two out of two cases). No MMR gene aberrations were found in seven cases of B-cell lymphocytic leukemia and two cases of mantle cell lymphoma of centrocyte-like type. These findings demonstrate that the expression rates of the hMSH2, hMLH1 and hPMS1 genes differ among various types of B-cell lymphoproliferative disorders, and suggest that MMR gene expression may be related to the natural history of these neoplasms. This study identified a higher incidence of MMR gene aberrations in lymphoma types characterized by aggressive biologic behavior, as compared to neoplasms with a more indolent course.