Myeloid Sarcoma of the Breast as Blast Phase of JAK2-Mutated (Val617Phe Exon 14p) Essential Thrombocythemia: A Case Report and a Systematic Literature Review.

INTRODUCTION: Myeloid sarcoma (MS) is a mass-forming proliferation of myeloid blasts. Frequently, it arises as blast phase of pre-existing myeloproliferative, myelodysplastic disorders or consequent to bone marrow transplant. Its molecular characterization has become an increasingly important requirement for the diagnostic definition of this solid leukemia. CASE PRESENTATION: Our case report concerns an MS arising in the breast of a woman with a previous diagnosis of JAK2-mutated essential thrombocythemia (Val617Phe exon 14p) mimicking, on histology, a lobular carcinoma of the breast. The immunohistochemical study of the neoplasm provided the key that solved the diagnostic doubt and the immunohistochemical evaluation of NPM protein expression, which turn out to be negative, provided a clear indication on the molecular status and prognosis of the disease. A year later, the neoplasm relapsed in the pelvic area. DISCUSSION: This diagnostic challenge led us to review the literature of the past 10 years concerning MS of the breast. To the best of our knowledge, this was the first case of MS of the breast occurring in a patient with a history of essential thrombocythemia and recurred in the pelvic region.

Promoting Laparoscopic Anterior Approach for a Very Low Presacral Primary Neuroendocrine Tumor Arising in a Tailgut Cyst.

BACKGROUND: Tailgut cysts are rare congenital lesions that develop in the presacral space. As they can potentially conceal primary neuroendocrine tumors, surgical excision is suggested as the treatment of choice. However, specific management guidelines have yet to be developed. A posterior approach is usually preferred for cysts extending to the third sacral vertebral body. Conversely, a transabdominal approach is preferred for lesions extending upward to achieve an optimal view of the surgical field and avoid injuries. CASE REPORT: Here, we report a case of a 48-year-old man suffering from perianal pain and constipation. Digital rectal examination and magnetic resonance imaging revealed a presacral mass below the third sacral vertebral body. A laparoscopic transabdominal presacral tumor excision was performed. The final histological diagnosis was a rare primary neuroendocrine tumor arising from a tailgut cyst. The postoperative course was uneventful, and no signs of recurrence were observed at the six-month follow-up. CONCLUSIONS: This study may help establish more well-grounded recommendations for the surgical management of rectal tumors, demonstrating that the laparoscopic transabdominal technique is safe and feasible, even for lesions below the third sacral vertebral body. This approach provided an adequate view of the presacral space, facilitating the preservation of cyst integrity, which is essential in cases of malignant pathologies.

Prognostic value of Bcl2 and Bcl6 in primary cutaneous large B-cell lymphoma: A systematic review and meta-analysis.

AIMS: To assess the prognostic value of Bcl2 and Bcl6 in primary cutaneous diffuse large B-cell lymphoma (pcDLBCL), through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to April 2021 for studies reporting Bcl2 and Bcl6 expression and survival outcomes in pcDLBCL series. Kaplan-Meier and Cox regression survival analyses with hazard ratio calculation were performed for overall survival (OS), with a significant p-value< 0.05. RESULTS: Eight studies with 148 patients were included. OS was significantly decreased in Bcl2-pos itive pcDLBCLs (5-year OS= 52.9 ± 5.2%) compared to Bcl2 negative pcDLBCLs (5-year OS= 86.6 ± 7.2%), with a HR of 4.615 (95% CI, 1.827-11.657; p = 0.001); no significant difference in OS was found between Bcl6-positive pcDLBCLs (5-year OS= 61.3 ± 6.5%) and Bcl6-negative pcDLBCLs (5-year OS= 56.8 ± 7.2%), with a HR of 0.789 (95% CI, 0.462-1.350; p = 0.388). CONCLUSIONS: In pcDLBCL, Bcl2 expression is a strong unfavourable prognostic marker; Bcl6 does not seem to be associated with survival instead. Further studies are necessary in this field.

Borrelia burgdorferi in primary cutaneous lymphomas: a systematic review and meta-analysis.

BACKGROUND: The association between Borrelia burgdorferi and primary cutaneous lymphoma is still unclear. This systematic review and meta-analysis aims to define the association of Borrelia burgdorferi with primary cutaneous lymphoma and its different entities. METHODS: Electronic databases were searched for all studies that assessed the presence of Borrelia burgdorferi DNA in specimens of primary cutaneous lymphoma. The association between Borrelia and primary cutaneous lymphomas was assessed with an odds ratio (significant p < 0.05); cutaneous specimens with no lymphoproliferative disorders were used as controls. A secondary analysis was performed to assess the prevalence of Borrelia infection in different lymphoma entities. RESULTS: Ten studies with 506 primary cutaneous lymphomas and 201 controls were included. The prevalence of Borrelia DNA positivity was highly heterogeneous among studies from different regions. Borrelia DNA positivity was significantly associated with primary cutaneous lymphomas (odds ratio = 10.88; p < 0.00001). The prevalence of Borrelia DNA positivity was similar among different entities (marginal zone: 7.3 %; follicular: 8.1 %; diffuse large B-cell: 7.5 %; mycosis fungoides: 8 %). CONCLUSIONS: Borrelia burgdorferi is significantly associated with primary cutaneous lymphomas, with no differences among the several lymphoma entities (both B-cell and T-cell), but with strong geographical differences. Molecular testing for Borrelia would be justified in patients with primary cutaneous lymphoma from endemic areas.

HIV prevalence in primary central nervous system lymphoma: A systematic review and meta-analysis.

HIV infection is considered a major risk factor for primary central nervous system lymphoma (PCNSL). However, the percentage of PCNSL that occurs in HIV + patients is not well defined. We aimed to assess the prevalence of HIV infection in patients with PCNSL through a systematic review and meta-analysis. Electronic databases were searched for studies assessing the presence of HIV infection in series of patients with PCNSL. Pooled prevalence of HIV infection in PCNSL was calculated, with a subgroup analysis based on the geographic area. Twenty-seven studies with 6422 patients were included. Overall, pooled prevalence of HIV infection among PCNSL patients was 6.1 % with high heterogeneity. In the subgroup analysis, pooled prevalence was 3.6 % in India with low heterogeneity, 30.2 % (overall) and 16.5 % (after 2000) in the USA with high heterogeneity, 5.7 % in Europe with high heterogeneity, 2.2 % in East Asia with null heterogeneity, 7.3 % in South America with moderate heterogeneity. In conclusion, only a minor part of PCNSL occurs in patients with HIV. The results stratified by geographic area reflect the different prevalence of HIV infection in the general population, except for India, probably due to the shorter life expectancy of HIV + patients.

Involvement of Helicobacter Pylori in Ocular Adnexa Lymphoma.

Helicobacter pylori has been proposed as a possible etiologic factor of ocular adnexa lymphoma (OAL), although with conflicting results. To assess the involvement of H. pylori in OAL, as (1) H. pylori DNA positivity on OAL specimens, and (2) prevalence of H. pylori gastric infection in patients with OAL. A systematic review of studies assessing H. pylori in patients with OAL was conducted by searching electronic databases from their inception to May 2019. Pooled positivity for H. pylori in OAL specimens detected by polymerase chain reaction, and pooled prevalence of H. pylori gastric infection, were calculated with 95% confidence interval (CI). Eleven studies with 308 patients were included. Pooled positivity for H. pylori was 16.8% in all OALs and 22.7% in MALT OAL, with high heterogeneity among studies. Pooled prevalence of H. pylori gastric infection in patients with OAL was 34.7%, with low statistical heterogeneity. In conclusion, H. pylori seems to be involved in a subset of OAL, but the heterogeneity found needs to be investigated in further studies. The prevalence of H. pylori gastric infection in patients with OAL does not seem to differ from that of the general population.

Hepatitis C virus in MALT-lymphoma of the ocular adnexa.

OBJECTIVE: Hepatitis C virus (HCV) has been proposed as a possible etiologic factor in ocular adnexal marginal zone lymphoma (OAML). We aimed to assess the prevalence of HCV infection in patients with OAML through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to August 2019 for studies assessing HCV seroprevalence in patients with OAML. Pooled prevalence of HCV infection was calculated with 95 % confidence interval (CI). Statistical heterogeneity among studies was quantified via the inconsistency index (I2). Funnel plot symmetry was used to assess the risk of bias across studies. RESULTS: Nine studies with 360 patients were included. Overall pooled prevalence of HCV in OAML was 12.7 %, with low statistical heterogeneity (I2 = 17.4 %) and with asymmetrical funnel plot. The studies clustered into two groups: 5 studies (3 from Italy and 2 multicenter with a major Italian contribution) showed a higher HCV prevalence in OAML (15.6 %), while the other 4 (from countries other than Italy) showed a lower prevalence (4.7 %); in both subgroups, statistical heterogeneity was null (I2 = 0%) and funnel plot was symmetrical. CONCLUSION: HCV might be a significant etiologic factor of OAML in Italy.

Sjögren Syndrome in Primary Salivary Gland Lymphoma.

OBJECTIVES: Sjögren syndrome (SS) is considered as a major etiologic factor for primary salivary gland lymphoma (SGL). However, the percentage of SGL that is caused by SS (and thus the real impact of SS on SGL epidemiology) is unclear. We aimed to assess the prevalence of SS in patients with SGL through a systematic review and meta-analysis. METHODS: Electronic databases were searched for studies assessing the presence of SS in patients with SGL. Pooled prevalence of SS in SGL was calculated, with a subgroup analysis based on histotype (mucosa-associated lymphoid tissue [MALT] vs non-MALT). RESULTS: Sixteen studies with 665 SGLs were included. Pooled prevalence of SS in SGL was 18.2%, with high heterogeneity among studies. In MALT SGL, the prevalence of SS was 29.5%, with moderate heterogeneity. In non-MALT SGL, the prevalence of SS was 0%, with null heterogeneity. CONCLUSIONS: SS seems to be responsible for a significant but minor portion of SGLs. SS appears involved in MALT-type SGL but not in other histotypes.

Clinical features associated with high pathological grade in primary thyroid lymphoma.

This study aimed to identify clinical features associated with high pathological grade (HG) in primary thyroid lymphoma (PTL), through a systematic review and meta-analysis. Electronic databases were searched for studies assessing PTL. Extracted data were age, sex, lymph node involvement, symptoms, lymphocytic thyroiditis, serum tumor markers; the association with HG was assessed by using odds ratio (OR), with a significant p-value<0.05. Twenty-four studies with 1916 PTLs were included. HG was significantly associated with age≤55 (OR = 0.54; p < 0.0001); female sex (OR = 1.31; p = 0.02), lymph node involvement (OR = 2.23; p < 0.00001), compressive symptoms (OR = 2.61; p < 0.0001), absence of lymphocytic thyroiditis (OR = 0.45; p = 0.0002), and increased LDH levels (OR = 4.90; p < 0.00001), but not with age>60 (OR = 0.74; p = 0.24), age>70 (OR = 1.16; p = 0.66), and B symptoms (OR = 1.30; p = 0.54). In conclusion, Age≤55, female sex, lymph node involvement, compressive symptoms and absence of lymphocytic thyroiditis may be predictive factors for HG in PTL. On the other hand, B symptoms does not seem to be associated with pathological grade.

Hashimoto Thyroiditis in Primary Thyroid Non-Hodgkin Lymphoma.

OBJECTIVES: To assess the prevalence of Hashimoto thyroiditis (HT) in primary thyroid lymphoma (PTL) and whether it differs between mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL). METHODS: Electronic databases were searched for studies assessing HT prevalence in PTL, based on antithyroid antibodies, clinical history, or pathology. Pooled prevalence of HT and its association with histotype (MALT or DLBCL) were calculated. RESULTS: Thirty-eight studies with 1,346 PTLs were included. Pooled prevalence results were 78.9% (any HT evidence), 65.3% (antithyroid antibodies), 41.7% (clinical history), and 64% (pathology). HT prevalence was significantly higher in MALT lymphoma than in DLBCL (P = .007) and in mixed DLBCL/MALT than in pure DLBCL (P = .002). CONCLUSIONS: Overall, 78.9% of patients with PTL have any HT evidence, but only half of these had been clinically followed. The difference in HT prevalence suggests that a subset of DLBCL may not derive from MALT lymphoma.

Prevalence of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis Determined by Molecular Testing in Ocular Adnexa Lymphoma Specimens.

OBJECTIVES: To assess the prevalence of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis in ocular adnexa lymphoma (OAL) determined by molecular testing in different countries and the potential association of Chlamydia infection with mucosa-associated lymphoid tissue (MALT) histotype by performing a systematic review and meta-analysis. METHODS: Electronic databases were searched for studies assessing the presence of Chlamydia in OAL. Pooled prevalence of the three Chlamydia species was calculated in each country. An odds ratio was calculated for the association between Chlamydia and MALT histotype, with a significant P < .05. RESULTS: Thirty-seven studies with 1,188 OALs were included. Pooled prevalence of C psittaci, C pneumoniae, and C trachomatis by country was done. Chlamydia infection was significantly associated with MALT histotype (odds ratio, 2.183; P = .027). CONCLUSIONS: The involvement of C psittaci in OAL is highly variable, with the highest prevalence in Italy and Korea. Chlamydia is associated with MALT histotype.

TLR4 down-regulation identifies high risk HPV infection and integration in head and neck squamous cell carcinomas.

TLRs are main actors of the innate immune response against HPV. There are very few studies on the role of TLRs mediated HPV clearance in Head and Neck oncology. Our aim was to evaluate whether TLR4 expression identifies HPV infection and/or HR-HPV integration status in oral and oropharyngeal cancers. By immunohistochemistry we assessed TLR4 levels in OSCC/OPSCC. To detect viral integration or episomic status In situ hybridization for HPV-DNA and Pyro-sequencing techniques have been performed. The relationship between TLR4 expression with HPV infection status has been investigated. ISH HPV positive samples have reported lower levels of TLR4 intensity than negative samples (p = .002). There was no statistical correlation between TLR4 intensity and PCR HPV results (p more than 0.0.5). Point-biserial correlation coefficient revealed significant association between TLR4 expression and HR-HPV integration status (p = .0001) and between TLR4 expression index and HR-HPV infection (p = .001). These data have shown that TLR4 down-regulation is strongly associated to both HPV-16 infection and its integration into the host DNA.

The role of EBV in the pathogenesis of Burkitt's Lymphoma: an Italian hospital based survey.

The exact worldwide incidence of Burkitt's lymphoma is not known. There are three distinct clinical variants of Burkitt's lymphoma, each manifesting differences in epidemiology, clinical presentation, morphology, biology and genetic features: the endemic (African), the sporadic (non-endemic), and the immunodeficiency-associated form. In particular, we reported data regarding Burkitt's lymphoma incidence in the world and across different European countries. Finally, we described clinic-pathological data of 48 Burkitt's lymphomas occurred in Italy from 2003 to 2013, in 4 different hospitals, two of which located in east side, and the other ones located in the west-coast. Forty Burkitt's lymphomas occurs in children (age range 3-12), and 8 were adulthood Burkitt's lymphomas (age range 18-87). In the pediatric group the Male:Female ratio (M:F) was of 4:1, whereas the group of the adult patients has a M:F of 1:1.67. Immunohistochemical detection of Latent Membrane Protein 1 (LMP1) expression and Epstein-Barr virus Encoded RNA (EBER) In Situ Hybridization (ISH) procedures have been performed. Lymphocyte B monoclonal spread has been demonstrated using a Polymerase Chain Reaction (PCR) based method to amplify Fragment Restriction FR1, FR2 and FR3 immunoglobulin heavy chains DNA fragments. Only 38 cases out of 48 were analyzed for LMP-1 showing various percentage of stained cells in 47.4% of the patients. Considering ISH for EBER detection results: 1 out 2 (50%) adult analyzed cases was positive, with 50% of stained tumor cells (this patient was a 22 years old female, coming from Napoli);15 out 24 (62.5%) children analyzed Burkitt's lymphomas resulted as positive for EBER;the overall positivity has been observed in 16/26 Burkitt's lymphomas (61.53%).Finally, EBV has been detected in children and adult patients, one of them with deregulation of the oncogene c-MYC by chromosomal translocation.