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Nedeljka Glavan,1 Jelena Roganović,2 Lana Glavan-Gačanin,3 Nives Jonjić4 1Department of Pediatrics Surgery, 2Department of Pediatrics Hematology and Oncology, University Hospital Centre Rijeka, 3Department of Obstetrics and Gynecology, University Hospital Centre Rijeka, 4Department of Pathology, School of Medicine, University of Rijeka, Rijeka, Croatia Abstract: Our experience in the treatment of a 4-year-old boy with cyclic neutropenia who was admitted for urgent appendectomy is described. The postoperative course was uneventful with high daily doses of granulocyte colony-stimulating factor and antimicrobial therapy. The purpose of this report is to highlight the importance of immediate appendectomy in neutropenic patients, wherein low absolute neutrophil count should not be considered as a contraindication for urgent surgical procedure. Keywords: cyclic neutropenia, appendectomy, absolute neutrophil count (ANC)

The distribution of the functional subsets of porcine T cells, the cytolytic/suppressor (Tc/s) and the helper/inducer (Th/i) cells was studied in cryostat sections of thymus, lymph nodes, tonsils, Peyer's patches, spleen and liver using the indirect immunoperoxidase technique. Three murine monoclonal antibodies (mAb) were used. The mAb 8/1 reacts with an antigen present on all T cells and on cells of the myeloid lineage; the antigen has not yet been characterized biochemically. The mAb 295/33 (anti- T8) binds to the porcine T8 antigen and defines the Tc/s subset, while mAb PT-4 (anti-T4) detects the porcine T4 antigen and defines the Th/i subset. Practically all thymocytes were stained by inAb 8/1. The majority of cortical thymocytes apparently co-expressed T8 and T4, whereas distinct fractions of medullary cells were labelled by either anti-T8 or anti-T4. In peripheral lymphoid organs all three mAb reacted with cells in the thymus-dependent areas and with cells scattered in the lymphoid follicles. In lymph nodes, tonsils and Peyer's patches, anti-T8 and anti-T4 each labelled approximately half of the cells stained by mAb 8/1. in the periarteriolar lymphoid sheath of the spleen, anti-T4 labelled more cells than did anti-T8. The reactivity of mAb 8/1 with the Kupffer cells of the liver demonstrated the expression of the 8/1 antigen on cells of the monocyte lineage. The T8 and T4 antigens could not be detected in acetone-fixed and paraffin-embedded sections, while the antigen recognized by mAb 8/1 remained preserved. Altogether, despite an inverted microanatomical structure of porcine lymph nodes, the frequency and distribution of T8+ and T4+ cells in thymus-dependent areas proved to be similar to those found in other species. [ABSTRACT FROM AUTHOR]

Glial tumors are the most frequent neoplasms of the central nervous system in adults and despite recent advances in diagnosis and treatment of the disease, the prognosis of glioma is poor. Therefore, there is a great need to identify new prognostic factors and potential immunotherapeutic targets. Members of the Nectin family of proteins are gaining significant attention as possible diagnostic and immunotherapeutic targets in many solid tumors, but they have not been extensively investigated in glial tumors. The aim of the present study was to evaluate the expression of Nectin-2 and Nectin-4 in glial tumors of different grades, and to assess their prognostic value. The results showed heterogeneous expression of Nectin-2 and Nectin-4 in tumor cells and neuropil, with significantly higher Nectin-2 expression compared to Nectin-4, but without differences among tumor grades. In addition, the expression of Nectin-2 and Nectin-4 was associated with shorter survival times in patients with grade II/III gliomas. These results suggest that Nectin-2 and Nectin-4 expression may be used as an independent prognostic indicator for patients with II/III gliomas. This study contributes to the development of personalized care for patients with glioma and provides a basis for further research on nectin-based immunotherapy for brain tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Metallothioneins (MTs) are phylogenetically old cysteine-rich proteins, which are implicated in a variety of physiological and pathological processes. Their growth-regulating, anti-apoptotic and anti-inflammatory functions have been attributed not only to intracellular free radical scavenging and to zinc and copper regulation but also to the ability of secreted MT to bind on surface lipoprotein receptor-megalin/LRP2, which enables the endocytosis of MT-I/II and a wide range of other functionally distinct ligands. In the present study, we analysed the expression pattern of both proteins in 55 cases of premalignant transformation of cervical squamous cells, i.e. in low- and high-grade squamous intraepithelial lesion (LSIL and HSIL). The data showed that in LSIL (cervical intraepithelial neoplasia CIN1; N = 25) MTs were present only in basal and parabasal cells and that megalin was only weakly expressed. In HSIL (CIN2; N = 15 and CIN 3/carcinoma in situ; N = 15), however, overexpression and co-localization of MT with megalin were found in the entire hyperplastic epithelium. Moreover, megalin immunoreactivity appeared on the glandular epithelium and vascular endothelium, as well as on lymphatic cells in stroma. Besides, multiple megalin-positive cells expressed phosphorylated Akt1, implying that MT- and/or megalin-dependent prosurvival signal transduction pathways might contribute to the development of severe cervical dysplasia. The data emphasize the diagnostic power of combined MT/megalin analysis in pre-cancer screening.

Hodgkin lymphoma (HL) is an uncommon malignancy usually limited to the lymph nodes and lymphatic system while extranodal involvement is much less common than in non-Hodgkin lymphoma. The current report presents an unusual case of primary classical HL (cHL), nodular sclerosis type with mixed cellularity in buttock soft tissue of 78-year old man. Primary lymphoma of the gluteal muscle is a rare disease and primary cHL is even rarer. In addition, to this unusual extranodal presentation, the present case highlight a diagnostic challenge in fine-needle biopsy masquerading a low grade sarcoma, primarily myxoinflammatory fibrosarcoma or an inflammatory lesion. However, surgical biopsy and immunohistochemistry guided correct diagnosis that was of major interest for further successful treatment.

The majority of endometrial carcinoma are diagnosed at an early stage and exhibit a favorable prognosis. However, 10% to 15% of ECs recur and the majority are type II tumors which are high-grade carcinomas. The epithelial-mesenchymal transition (EMT) has been considered as a fundamental step for the development of the invasive phenotype of cancer cells. During EMT, many of epithelial surface markers, primarily E-cadherin disappear, and mesenchymal markers including N-cadherin gain. This feature resides predominantly at the invasive front (IF) of the tumor. Therefore, we examined the immunohistochemical expression of E-cadherin and N-cadherin at the IF, in central areas of the tumor and lymphovascular space, in type I and type II endometrial carcinoma. The association of each protein with the clinicopathologic features was also evaluated. Our results confirmed a stronger E-cadherin immunostaining in type I tumors indicating that the loss of E-cadherin may be responsible for a more aggressive behavior of type II ECs. In both types, E-cadherin was strongly expressed in central areas and the reactivity decreased toward the IF. On contrary, N-cadherin was overexpressed at the IF confirming an inverse relationship between these markers. In addition, a decrease in E-cadherin expression was observed in cells within the lymphovascular space. Downregulation of E-cadherin was associated only with high-grade tumors while no correlations between both markers and other clinicopathologic features were found. Our results confirm that EMT occurs at the IF that represents a critical interface between the tumor and the host.

The aim of this report is to present a case of a patient with a recurrent nasal cavity amelanotic melanoma (AM), with emphasis on diagnosis and therapy options of this clinical entity. A 65-year-old female patient presented with pain in the right cheek region and nasal obstruction. In 2013, she was diagnosed with mucosal melanoma (MM) of the left nasal cavity. After endoscopic surgery and radiotherapy, the patient was followed by the oncology team. Five years after the initial diagnosis, rhinoscopy showed a tumorous formation in the right nasal cavity. The tumor mass was without black discoloration and was the same color as the surrounding nasal mucosa. Microscopic examination after biopsy of the tumor confirmed amelanotic MM. The patient underwent an additional endoscopic surgery. A complete standard diagnostic workup for MM found metastases in head and neck lymph nodes, on both sides. MMs of head and neck are uncommon malignancies. Unique biology of MM cells causes a high rate of recurrences. This report presents an example of recurrent AM of the nasal cavity, in treatment with checkpoint inhibitor (pembrolizumab), which could provide a good therapy option for patients with MM., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest.

Background: Proliferation rate is a major determinant of the biologic behavior of the tumor and provides information that can be used to guide treatment decisions., Methods: This ring study included 27 pathologists from 14 Institutions, in order to assess inter-observer concordance between pathologists in Croatia. We analyzed Ki-67 proliferative index on ten randomly selected breast cancer samples comparing consistency between visual assessment using light microscopy compared to digital image analyses results from one central laboratory as a referral value., Results: When we analyzed Ki-67 as numeric value high concordance rate was found between Ki-67 score visually assessed in all participating Institutions compared to referral value assessed by digital image analysis (ICC 0.76, 95% CI 0.58-0.91), and Krippendorff's alpha was 0.79 (95% CI 0.58-1.00). Concordance was better in slides with higher Ki-67 values. When we categorized Ki-67 values according to generally accepted 20% cut-off value we noticed the lower concordance rate among participants in our study., Conclusion: Proliferation remains one of the most important parameters for tumor characterization helpful in making clinical decisions, but it should be used with great caution. Standardization of the Ki-67 assessment is essential and proliferating index should be expressed as exact numeric value. For patients with proliferative index near the cut-off value, other factors must be considered in making clinical decisions.

An association between autoimmune events, as well as the development of antiphospholipid (aPL) antibodies and lymphoproliferative disorders is well recognized. We present the patient with coagulation abnormalities and non-Hodgkin lymphoma (NHL), primarily diagnosed as nodal marginal zone B-cell lymphoma (NMZL), and in relapse as diffuse large B-cell lymphoma (DLBCL). In the follow-up period, the patient simultaneously developed different aPL antibodies. The presence of aPL antibodies in NHL is frequent but it is not common in the NMZL. The aim of the present case report is to highlight the possible underlying increase of aPL antibodies in NMZL patients with coagulation tests abnormalities., (Copyright © 2018. Published by Elsevier GmbH.)

Acid ceramidase (ASAH1) has been implicated in the progression and chemoresistance in different cancers. Its role in colon cancer biology and response to standard chemotherapy has been poorly addressed so far. Here, we have investigated ASAH1 expression at the protein level in human colon cancer cell lines and tissues from colon cancer patients, and have examined in vitro the possible link between ASAH1 expression and functional activity of p53 protein whose inactivation is associated with the progression from adenoma to malignant tumour in colon cancer. Finally, we have explored the role of ASAH1 in response and resistance mechanisms to oxaliplatin (OXA) in HCT 116 colon cancer cells. We have demonstrated that human colon cancer cells and colorectal adenocarcinoma tissues constitutively express ASAH1, and that its expression is higher in tumour tissues than in normal colonic mucosa. Furthermore, we found an inverse correlation between ASAH1 expression and p53 functional activity. Obtained data revealed that ASAH1 was involved in HCT 116 cell response to OXA and that anti-proliferative, pro-apoptotic, anti-migratory and anti-clonogenic effects of OXA could be significantly increased by combination treatment with ASAH1 inhibitor carmofur. Increased OXA sensitivity was associated with downregulation of signalling involved in acquired resistance to OXA in colon cancer, in particular transglutaminase 2 and β1 integrin/FAK, which resulted in the suppression of NF-κB and Akt. Thus, combination of OXA with ASAH1 inhibitors could be a promising strategy to counter chemoresistance and improve treatment outcome in advanced colon cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Plasmablastic lymphoma (PBL) is relatively new clinical entity described as a distinct subtype of diffuse large B-cell lymphoma (DLBCL). It is characterized by its aggressive nature and proliferation of large neoplastic cells resembling immunoblasts including cells with more obvious plasmacytic differentiation. In this case report, we describe an unexpected finding of PBL associated with a mature cystic teratoma of the ovary in a young immune competent woman., Case Presentation: A 19-year old woman was admitted to the hospital with generalized lymphadenopathy, a pelvic tumor mass measuring 35 × 30 cm and a 4 cm lump in her right breast. She underwent a right salpingo-oophorectomy, lymphadenectomy, splenectomy, omentectomy, and a right breast lumpectomy. On macroscopic examination the right ovary was replaced by a thick-walled multilocular cystic tumor. Upon incision, the cysts were filled with thick, greasy sebaceous material and hair and there were several solid nodules within the cyst walls. Histological examination revealed a mature cystic teratoma and malignant non-Hodgkin lymphoma (NHL) within the solid nodules. Tumor tissue from the right breast, spleen and lymph nodes, all had the same histological, NHL morphology. After extensive immunostaining, a diagnosis of PBL was made. Following surgery, the patient was treated with different chemotherapy regimens, without any significant regression of the disease, and died of multiple organ failure., Conclusions: Primary NHL of the ovary is relatively rare occurrence while secondary involvement by lymphoma is much more common. PBL is a rare lymphoma, primarily reported in the jaw and oral mucosa, but also documented in extra-oral sites. To the best of our knowledge, this is the first case described in a mature ovarian cystic teratoma. Although the patient was HIV-negative and immune competent, she had progressive disease and died despite aggressive chemotherapy 11 months after the initial diagnosis.

Since there are no standardized protocols regarding the detection of microscopic melanoma deposits in sentinel lymph nodes (SLN), the aim of this study was to present our experience with intraoperative cytological evaluation of SLN in patients with melanoma. The study included 475 SLN biopsies (SLNB) from 201 patients with primary cutaneous melanoma of intermediate thickness. Each lymph node was cut in half; touch imprint cytology (TIC) preparations of all cut surfaces were performed and stained according to a modified May-Grünwald-Giemsa method. The results were compared to definitive postoperative histology. Twenty of 25 SLNB positive on TIC proved to be metastatic when compared to definitive histology. Most of 32 SLN that were suspicious but not diagnostic on TIC were proven negative (23/32, 71.8%), while 7 nodes had metastases (one micrometastasis and one with isolated tumor cells only). The majority (94%) of SLNBs negative on TIC remained negative on final histology, while 6% or 25 nodes were positive, mostly with micrometastases or isolated tumor cells (17/25). In frozen sections performed in cases of suspicious or positive SLN cytology, metastasis was confirmed in 80% of positive and in 21.9% of suspicious TIC. Altogether, 49% (27/55) of positive SLNB were identified intraoperatively in 57% (24/42) of patients, and in those cases a complete regional lymph node dissection was performed in the first step. TIC assessment of SLNB with 99% specificity and 57% sensitivity for intraoperative identification of metastasis is useful and beneficial for avoiding a second operative procedure.

Simultaneous occurrence of T-cell and B-cell neoplasms is rare, and etiologic relationships between these 2 malignancies are poorly understood. We describe the case of a 66-year-old woman who was admitted to the hospital because of fever, hemoptysis, lymphadenopathy, and skin rash. Enlarged lymph nodes in axillary, pectoral, paratracheal, and periportal regions as well as slight hepatomegaly and splenomegaly were confirmed. A peripheral blood smear revealed rouleaux formation and numerous circulating plasma cells, with plasmacytoid lymphocytes. Immunofixation-electrophoresis detected a monoclonal band defined as immunoglobulin (IgG)-lambda light chains with broad-band polyclonal IgA. The patient died from abrupt splenic rupture before diagnostic work-up was finished. Postmortem examination revealed infiltration of atypical lymphoid cells exhibiting high proliferative activity admixed with typical and atypical plasma cells in several organs. Thus, plasma cell leukemia (IgG-lambda) as a rare and aggressive variant of plasma cell myeloma in the present case was associated with aggressive peripheral T-cell lymphoma and polyclonal (IgA) plasmacytosis.