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Myelodysplastic syndromes (MDS) are clonal disorders of the bone marrow characterized by ineffective haematopoiesis and an intrinsic predisposition to evolve into acute myeloid leukaemia. Impaired haematopoiesis manifests clinically with worsening cytopenia(s) responsible of patients’ symptoms and morphologically with myelodysplasia and with the progressive accumulation of immature myeloid cells and blasts. Therefore, the diagnosis of MDS is always an integrated process which requires the combination of clinical and morphologic data. In recent years a larger body of knowledge has accumulated regarding the molecular events occurring in MDS, including chromosomal abnormalities and somatic gene mutations. So called “myeloid gene panels” and fluorescence in situ hybridization panels have joined conventional karyotyping in the diagnostic workup of MDS. None of these alterations is disease-specific; however, their identification supports the existence of a clonal disease, especially in cases with subtle dysplasia and/or mild cytopenia, and provides prognostic information for disease stratification and treatment.

The 2016 revised 4th edition of the World Health Organization classification of hematopoietic neoplasms updated the diagnostic criteria for chronic myelomonocytic leukemia (CMML). Persistent peripheral blood monocytosis of at least 1 × 109 /L and a percentage of monocytes ≥10% of the circulating white blood cell count (WBC) are both prerequisite criteria for this diagnosis. CMML represents the prototype of "overlapping" myeloid neoplasms with concurrent myeloproliferative and myelodysplastic features. However, clinical presentation is heterogeneous, with cases showing prevailing "dysplastic" features and others a predominant "proliferative" phenotype. Accounting for this diversity, two variants of CMML are recognized: "dysplastic" CMML defined by WBC

Rationale Percutaneous core needle biopsy (CNB) of the spleen is rarely performed, due to concerns about its complications and low diagnostic yield. However, this procedure represents a potentially useful diagnostic tool, especially in patients with splenomegaly and no definitive diagnosis after a clinical and radiological work-up. Methods and results We report the data on a cohort of 45 radiologically guided percutaneous core needle biopsies of the spleen from 44 patients performed at two centres. Platelet count and prothrombin time were within normal limits in all patients at the time of the procedure. The biopsy was ultrasound-guided in all cases except one, which was guided by computed tomography. An 18G needle was used in 82% of the cases, followed by 16G (10.2%) and 20G (7.8%) needles. The biopsy provided sufficient material for histological examination (including immunohistochemical studies) in 41 cases (91.1%). Haematological malignancies were most commonly diagnosed (52.3%); diffuse large B cell lymphoma (DLBCL) was the most frequent, followed by splenic marginal zone lymphoma (SMZL). For the most recent cases of DLBCL, the CNB provided sufficient material for fluorescence in-situ hybridisation to assess the status of MYC, BCL2 and BCL6. This allowed the identification of a case of high-grade B cell lymphoma with MYC and BCL2 rearrangement. Major complications were not reported; minor complications occurred in three cases (6.7%). Conclusions Our data demonstrate that radiologically guided percutaneous CNB should be considered as a valid diagnostic tool, as it provides quick and reliable histological diagnoses avoiding the complications and risks of splenectomy.

GATA binding protein 1 (GATA1) is a transcription factor essential for effective erythropoiesis and megakaryopoiesis. Two isoforms of GATA1 exist, derived from alternative splicing. "GATA1" is the full length and functionally active protein; "GATA1s" is the truncated isoform devoid of the activation domain, the function of which has not been fully elucidated. Reduced megakaryocytic expression of GATA1 has been linked to impaired hematopoiesis and bone marrow fibrosis in murine models and in vivo in patients affected by primary myelofibrosis (PMF). However, data is limited regarding GATA1 expression in other myeloproliferative neoplasms (MPN) such as pre-fibrotic PMF (pre-PMF), polycythemia vera (PV) and essential thrombocythemia (ET) and in their respective fibrotic progression. To assess whether an immunohistologic approach can be of help in separating different MPN, we have performed a comprehensive immunohistochemical evaluation of GATA1 expression in megakaryocytes within a cohort of BCR-ABL1 negative MPN. In order to highlight any potential differences between the two isoforms we tested two clones, one staining the sum of GATA1 and GATA1s ("clone 1"), the other staining GATA1 full length alone ("clone 2"). At the chronic phase, a significant reduction preferentially of GATA1 full length was seen in pre-fibrotic PMF, particularly compared to ET and PV; no significant differences were observed between PV and ET. The fibrotic progression of both PV and ET was associated with a significant reduction in GATA1, particularly affecting the GATA1 full length isoform. The fibrotic progression of pre-PMF to PMF was associated with a significant reduction of the overall GATA1 protein and a trend in reduction of GATA1s. Our findings support a role of GATA1 in the pathogenesis of BCR-ABL1 negative MPN, particularly in their fibrotic progression and suggest that the immunohistochemical evaluation of GATA1 may be of use in the differential diagnosis of these neoplasms.

Vascular neoplasms are among the most common conditions affecting the spleen. The majority of these are idiopathic, benign in nature and asymptomatic and therefore treated with a conservative management. Only rare cases cause splenomegaly and/or chronic consumption coagulopathies, thus requiring splenectomy. Among these, the most common is splenic hemangioma, followed by littoral cell angioma and lymphangioma. Peliosis is a peculiar tumor-like non-neoplastic vascular lesion that diffusely affects the spleen and frequently presents with concomitant hepatic involvement. As a distinctive feature, peliosis can occur as a secondary manifestation of infections, malignancies and in individuals using certain drugs. On the opposite spectrum of clinical behavior lies splenic angiosarcoma, a vascular endothelial malignancy with aggressive presentation and poor prognosis. In some cases the endothelial nature of this neoplasm may not be evident on routine histologic examination and immunohistochemistry is used to disclose such phenotype. The term hemangioendothelioma is rarely used to describe borderline vascular neoplasms which appear more aggressive than conventional hemangiomas, but that do not entirely fulfill the diagnostic criteria for angiosarcoma. Some of these neoplasms coexpress endothelial and histiocytic markers and therefore have been proposed as the borderline counterpart of littoral cell angioma. The existence of hemangioendothelioma as a diagnostic entity per se is debated and this diagnosis should be rendered with caution. The current review aims at highlighting the main histologic features of vascular neoplasms and non-neoplastic vascular lesions of the spleen.

The spleen can be affected by several different non-hematopoietic neoplasms as well as pseudoneoplastic lesions. Generally such conditions affect asymptomatic adults and are detected only as incidental findings; in a minority of the cases vague, unspecific symptoms including abdominal discomfort can occur. Most of these conditions present as a "solitary splenic mass" and have been traditionally diagnosed on partial or total splenectomy, which also represents the most common therapeutic strategy; however, the increasing use of splenic needle biopsies for such lesions creates new diagnostic challenges for pathologists. Splenic cysts (including true cysts, pseudocysts and parasitic cysts) and hamartomas are common benign proliferations which generally pose little problems in their identification. More challenging is the diagnostic workup of "spindle cell and inflammatory rich" lesions of the spleen, whose correct identification is crucial. Indeed, some of these are considered reactive (such as sclerosing angiomatoid nodular transformation of the spleen), whilst others are clonal in nature, the main example being represented by the so called "inflammatory pseudotumour- like follicular/fibroblastic dendritic cell sarcoma". A further degree of complexity is represented by the detection of the Epstein-Barr virus (EBV), which is invariably present in inflammatory pseudotumour- like follicular/fibroblastic dendritic cell sarcoma, but also in other proliferations including the rare "EBV- related smooth muscle tumor of the spleen". Finally, the spleen can host rare dendritic/reticulum cell sarcomas and metastases from extrasplenic malignancies. The current review aims at highlighting the main histologic features of non-hematopoietic and non-vascular neoplasms as well as pseudoneoplastic lesions of the spleen.

ObjectivesAdult primary cervical rhabdomyosarcoma is a very rare disease and data regarding treatment are sparce. The goal of this study was to report on our experience with the management of this rare entity, along with an evaluation of the literature.MethodsWe conducted a review of the medical records at four centers from January 1990 to December 2017. We reviewed clinical characteristics including age at diagnosis, BMI, medical history and tumor stage, as well as treatment in the primary and recurrent settings and follow-up data. We reclassified tumors according to the Intergroup Rhabdomyosarcoma Study (IRS) clinical group.ResultsA total of 15 patients were included in the analysis. Median age at diagnosis was 35 years (range 17–55). Median tumor size at presentation was 5 cm (range 3–10). Eleven patients had the embryonal variant, including five showing the botryoid subtype. Four patients had a pleomorphic rhabdomyosarcoma. Eleven patients had disease classified as IRS Clinical Group I, while the remaining four fell into groups II or III. Fertility-sparing treatment was offered to five patients. Primary treatment types were: surgery alone in eight patients, surgery followed by adjuvant chemotherapy in six patients, and neoadjuvant chemotherapy in two patients. The main risk factors for relapse were: IRS clinical group greater than I, tumor size greater than 5 cm, lymph nodal involvement, and non-embryonal histology. At a median follow-up of 35 months (range 3–282), we observed a 5-year overall survival rate of 78.2% and a progression-free survival of 58.2%. No patient in the IRS I group died of the disease. Three out of four patients in the IRS II-III group died of the disease (survival range 5–16 months following treatment).ConclusionOur data show that cervical rhabdomyosarcomas account for at least two prognostic groups, demonstrating the existence of low-risk and high-risk patterns. The best predictor of prognosis appearsd to be the IRS clinical group classification system. IRS Group I tumors had an overall good prognosis and rarely recurred; when they did recur they were mainly local, following conservative treatment.

The term myelodysplastic/myeloproliferative neoplasm (MDS/MPN) refers to a group of clonal hematopoietic neoplasms with overlapping clinical, morphologic and genetic myelodysplastic and myeloproliferative features observed at the time of first presentation. Impaired hematopoiesis morphologically associated with evidence of myelodysplasia manifests clinically with cytopenia/s. Simultaneously, myeloproliferation is seen within the bone marrow and leads to cytosis in the peripheral blood. The diagnostic category of MDS/MPN encompasses a heterogeneous group of diseases which share similarities among them, but at the same time have distinct clinical and pathologic features and eventually diverse prognosis; such differences justify their separation in a classification scheme. In the era of genetic and genomic tests, their distinction from conventional myelodysplastic syndromes or myeloproliferative neoplasms still relies on close clinocopathological correlation, with evaluation of both peripheral blood and bone marrow samples being essential in this sense. A multiparametric integration of clinicopathologic data and cytogenetics and molecular genetics results is the preferred diagnostic approach.