Background/Aim: The neuroendocrine tumor (NET) proliferation-based grading system (ENETS/WHO) for gastroenteropancreatic (GEP) tumors has proved reliable for prognostic stratification. To date, concerns exist regarding Ki-67 heterogeneity within the tumor and little is known on whether grade varies between primary and secondary sites. As tumor heterogeneity may have a significant impact on clinical management, our aim was to retrospectively evaluate Ki-67 on a series of GEP NETs in order to establish whether there is variability in different samples of the same lesion or between primary and metastatic disease (local/distant, synchronous/metachronous). Methods: Sixty patients with multiple samples of tumor were accrued from a total of 338 GEP NETs; 44 of them also had tissue from local/distant metastases and a further 5 had multiple metastatic foci from unknown primary tumors. Immunohistochemistry for Ki-67 was performed on all paraffin blocks from both primary and metastatic tumors. Results: Intratumor Ki-67 heterogeneity sufficient to change grade at first diagnosis was seen in 3/60 cases (5%). Out of 49 patients with primary NETs and/or multiple metastases, discrepancy in grade between sites was identified in 19 (39%) cases and in particular in 11/47 (23%) and in 10/12 (83%) patients with synchronous and metachronous metastases, respectively (p = 0.0002). Change in grade was more frequent in distant compared to locoregional metastases (p = 0.024) and in particular in distant sites other than the liver (p = 0.006). Conclusions: NETs show frequent differences in grade between primary sites and their synchronous/metachronous metastases; assessment of Ki-67 at all sites may prove to be significant for patient management.

Pityriasis lichenoides (PLs) is an uncommon skin disease of unknown etiology. In recent years, an atypical form of PL has been described, showing overlapping features with mycosis fungoides (MF) and lymphomatoid papulosis. We studied 66 patients with an initial histopathologic diagnosis of PL (M:F=34:32; median age, 25 y; range, 7 to 85 y). According to clinical and phenotypic features, cases were classified into 4 categories: (1) Conventional PL (characteristic clinical features of PL without phenotypic aberrations) (n=20; M:F=8:12; median age, 37 y; range, 9 to 74 y); (2) Atypical form of PL (characteristic clinical features of PL with phenotypic aberrations) (n=25; M:F=16:9; median age, 21 y; range, 7 to 72 y). Four of these patients subsequently developed MF; (3) Lymphomatoid papulosis (waxing and waning lesions and positivity for CD30) (n=10; M:F=4:6; median age, 41 y; range, 16 to 83 y); (4) MF (clinical features typical of MF) (n=11; M:F=6:5; median age, 17 y; range, 8 to 85 y). Molecular analyses of clonality of the infiltrate did not reveal relevant differences among these 4 groups. Our study suggests that patients with an initial histopathologic diagnosis of PL may belong to different groups, showing that clinicopathologic correlation and complete phenotypic analyses are paramount in order to achieve proper classification. Although the relationship between PL and MF is yet a matter of debate, at the present state of knowledge, patients with a clinicopathologic presentation consistent with PL but with aberrant phenotypic features should be monitored in order to detect a possible evolution into MF.

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Spontaneous splenic rupture (SSR) is a rare life-threatening emergency. In hematological settings, it is uncommon in acute myeloid leukemia (AML). We report an atypical case of SSR in a 73-year-old male with AML where a prompt imaging ultrasound assessment played a key role. Performed noninvasively at bedside, it allowed rapid imaging diagnosis, confirming its essential role even in the presence of hematological disease.

Objectives The use of Bruton’s tyrosine kinase (BTK) inhibitors has changed the clinical history of patients with chronic lymphocytic leukemia (CLL) in both naïve and relapsed/refractory settings. “Accelerated” chronic lymphocytic leukemia (a-CLL) is a relatively rare form of CLL representing less than 1 % of all CLL cases. a-CLL patients usually have a more aggressive course and a reduced overall survival was reported with conventional chemo-immunotherapy approaches. Methods The role of Bruton Tyrosine Kinase-inhibitor, ibrutinib, in a-CLL is well established with encouraging preliminary results. Results We report a case of a-CLL-treated first-line with second-generation BTKi, acalabrutinib with a prompt clinical response. As known, it is the first literature report on acalabrutinib in a-CLL highlighting the role of second-generation BTKi also in this high-risk setting. Conclusions Target therapies (Bruton Kinase inhibitors and Bcl2 inhibitors) have improved the therapeutic landscape of CLL. The availability of therapeutic targets requires greater diagnostic accuracy to choose the most appropriate therapy for each patient.