A patient with widespread skin lesions presenting with massive pleural effusion.

Mycosis fungoides is the most commonly seen type of cutaneous T-cell lymphoproliferative disease. While mycosis fungoides is linked to an increased risk of developing secondary malignancies, the occurrence of B-cell-originated disease in association with it is exceedingly rare. A 66-year-old male with persistent papillomatous skin eruption was admitted due to dyspnea. Chest X-ray, positron emission tomography, and chest computed tomography revealed axillary and mediastinal lymph node enlargement and right lower pulmonary lobe infiltration along with right-sided massive pleural effusion. Histological and immunohistochemical findings of pleural biopsy and axillary lymph nodes suggested a diagnosis of pulmonary extranodal marginal zone lymphoma. Skin biopsies from the abdomen, chest, and legs revealed CD4/CD8 double-positive patch stage of mycosis fungoides. After completing six cycles of chemotherapy, complete remission of lymphoma was achieved, with the skin eruptions remaining unchanged. Herein, the authors present a unique case of concomitant diagnoses of mycosis fungoides and marginal zone B-cell lymphoma of the respiratory system to emphasize the importance of careful evaluation of each finding.

A rare case of orbital mantle cell lymphoma presenting as a well-demarcated mass on magnetic resonance imaging.

A 71-year-old male presented with painless and slowly progressive proptosis of the right eye. The patient had no history of cancer and was in good health. Orbital magnetic resonance imaging showed a well-demarcated, slightly lobulated intraconal orbital mass hypo-isointense on T1- weighted and isointense on T2-weighted images, demonstrating contrast enhancement in the right orbit. The lesion had a central cavitary region. An anterior orbitotomy with lower lid crease incision was performed and the lesion was excised in toto. Histopathologic examination revealed diffuse infiltration of monomorphic population of small lymphoid cells. Immunohistochemical staining demonstrated diffuse and strong positivity for CD20, CD5, and cyclin D1. Histopathological and immunohistochemical findings were consistent with mantle cell lymphoma. Positron emission tomography-computed tomography did not show systemic involvement. The patient underwent orbital external beam radiotherapy (36 Gy). There was no recurrence and/or systemic involvement at 2.5 years follow-up.

Myeloid sarcomas: a clinicopathologic study of 20 cases.

OBJECTIVE: Myeloid sarcoma is a tumoral mass of mature or immature myeloid blasts in extramedullary anatomic locations. It can be seen de novo or in association with acute myeloid leukemia, myeloproliferative neoplasias, or myelodysplastic syndrome. Isolated myeloid sarcoma can be seen as a relapse in cases with allogenic bone marrow transplantation. Although it may involve any tissue in the body, the most common locations are skin, soft tissues, lymph nodes, and the gastrointestinal tract. Immunohistochemically, most cases show myelomonocytic or pure monoblastic differentiation. We reviewed the clinicopathological features of 20 cases of myeloid sarcoma diagnosed in our institute in view of the literature. MATERIALS AND METHODS: The cases diagnosed between 2005 and 2012 at the Ankara University Faculty of Medicine, Department of Pathology, were selected. Clinicopathological findings including the age and sex of the patients; symptoms; anatomic location; accompanying hematological disease; and the morphological, immunohistochemical, and cytogenetic features of the cases were noted. RESULTS: Sixteen of the patients were male and 4 were female. The median age at diagnosis was 47 years. The most commonly involved locations were the lymph nodes and skin. Immunohistochemically, eleven cases were of the myelomonocytic and 7 cases were of the myeloid phenotype, whereas 2 cases showed pure monoblastic differentiation. The median follow-up period for the 18 cases with known clinical data was 33 weeks. Five patients died of the disease in an average of 36 weeks. CONCLUSION: Myeloid sarcoma is a rare presentation of leukemias, myeloproliferative neoplasias, or myelodysplastic syndrome, composed of immature myelomonocytic cells in extramedullary tissues. It may present with variable morphological and phenotypic features, always creating a challenge in pathological diagnosis.

Epstein-barr virus-negative post-transplant lymphoproliferative diseases: three distinct cases from a single center.

Three cases of Epstein-Barr virus (EBV)-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

Evaluation of late effects during a 21-year follow-up of pediatric Hodgkin lymphoma survivors: Experience of a pediatric cancer center in Turkey, as a developing country model.

BACKGROUND: Long-term survivors of Hodgkin lymphoma (HL) are at risk of developing a range of late effects, with a second malignant neoplasm and cardiovascular diseases being the leading causes of death in these patients. The present study aims to evaluate the late side effects in children with HL. MATERIALS AND METHODS: Out of 53 HL patients, we assessed the long-term effects of childhood HL survivors (HLSs; n = 50) diagnosed between 1998 and 2019. Patient data related to chronic health conditions, and sociodemographic characteristics were compared with their siblings (n = 56). RESULTS: The cumulative overall survival (OS) at 1, 5, and 10 years from diagnosis was 98.1 ± 1.9%, 93.3 ± 3.8%, and 93.3 ± 3.8%, respectively. Groups of HLSs and their siblings were matched according to age and gender. Compared with siblings, survivors had will be changed as 'a higher frequency of nephrotoxicity (P = 0.02)', cardiotoxicity (P = 0.12), thyroid dysfunction (P = 0.001), health care service usage (P < 0.01), limitation of physical function (P = 0.01), and pulmonary disease (P = 0.01). The control group of siblings had a higher incidence of marital status (P < 0.01), parenthood (P = 0.01), and smoking habit (P = 0.03). Thyroid dysfunction was associated with neck radiotherapy (P < 0.01). No secondaryneoplasm was detected. In relapsed, refractory setting (n = 10), autologous transplantation (n = 9) is performed after a complete remission. Brentuximab vedotin with or without bendamustine and rituximab is also used in selected patients. CONCLUSIONS: Increased number of chronic health conditions and social problems point to the significance of long-term follow-up of HLSs. We are currently preparing a survivorship guideline appropriate for Turkey's conditions. IMPLICATIONS FOR CANCER SURVIVORS: Renal, heart, pulmonary impairment, thyroid dysfunction, limitation in physical functioning, and deterioration in social status (marriage, having children, education).

Anterior segment optical coherence tomography in ocular surface tumours and simulating lesions.

This study aims to systematically review the reported literature on the use of anterior segment optical coherence tomography (AS-OCT) in ocular surface tumours and simulating lesions. A systematic literature search was done using PubMed, Scopus, and Web of Science databases between January 2002 and December 2021. On AS-OCT, ocular surface squamous neoplasia typically demonstrate epithelial thickening, epithelial hyperreflectivity, and an abrupt transition between normal and abnormal epithelium. Conjunctival nevi usually show mildly hyperreflective epithelium of normal thickness, internal hyperreflectivity, and intralesional cysts which is the hallmark of this tumour. Primary acquired melanosis presents with normal thickness epithelium, basal epithelial hyperreflectivity, and absence of cysts. Conjunctival melanoma demonstrates hyperreflective normal/thickened epithelium, hyperreflective basal epithelium, internal hyperreflectivity, and absence of intralesional cysts. Conjunctival lymphoma shows homogenous, low-medium reflective subepithelial lesions with smooth borders, and dot-like infiltrates. Benign reactive lymphoid hyperplasia findings are similar to lymphoma but the infiltrates are more hyperreflective compared to lymphoma. Pterygium shows thickened conjunctival epithelium, epithelial hyperreflectivity, and subepithelial wedge-shaped hyperreflective tissue separated from the overlying epithelium by a cleavage plane. Pinguecula demonstrates mildly thickened epithelium and similar findings with pterygium but does not extend beyond the corneal limbus. This review shows that AS-OCT, as a noninvasive tool, has potential uses in the differential diagnosis of ocular surface tumours and simulating lesions. Major limitations of AS-OCT include limited visualization of the posterior border of thick, keratinized, and pigmented tumours and lack of assessment of large conjunctival tumours in a single cut.

Relevance of Additional Immunohistochemical Markers in the Differential Diagnosis of Small B-Cell Lymphomas: A Case-Control Study

Objective: Clinical and pathological differential diagnosis of small B-cell lymphomas (SBCLs) is still controversial and may be difficult due to their overlapping morphology, phenotype, and differentiation to plasma cells. We aimed to examine the expression of the immune receptor translocation-associated protein 1 (IRTA1), myeloid cell nuclear differentiation antigen (MNDA), lymphoid enhancer-binding factor-1 (LEF1), and stathmin 1 (STMN1) markers in SBCL cases involving different sites that may have plasma cell differentiation. Materials and Methods: We studied 154 tissue samples with lymphoma involvement from 116 patients and evaluated the staining distribution of the markers. Expressions were evaluated in 21 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 7 follicular lymphoma (FL), 14 nodal marginal zone lymphoma, 17 extranodal marginal zone lymphoma, 55 splenic marginal zone lymphoma, 22 marginal zone lymphoma-not otherwise specified, and 18 lymphoplasmacytic lymphoma/Waldenström macroglobulinemia cases by immunohistochemistry. Results: The results confirmed that LEF1 was the most sensitive and specific marker for CLL/SLL and STMN1 was the most sensitive and specific marker for FL (p<0.001). MNDA and IRTA1 were useful markers to distinguish marginal zone lymphomas. Conclusion: Our results suggest that LEF1 for CLL/SLL and STMN1 for FL are reliable markers. LEF1, MNDA, STMN1, and IRTA1 are helpful with other routinely used immunohistochemical markers in a diagnostic algorithm considering their limitations.

Loss of CTNNB1 exon 3 in sclerosing angiomatoid nodular transformation of the spleen.

Sclerosing angiomatoid nodular transformation (SANT) is a rare vascular lesion of the spleen. Although several hypotheses have been suggested, the etiopathogenesis of SANT remains unknown. It is also unclear whether SANT is a reactive or a neoplastic lesion. Since CTNNB1 (ß-catenin gene) exon 3 mutations were frequently detected in some rare fibrovascular lesions, we aimed to investigate the presence of oncogenic CTNNB1 mutations in SANT cases. For this purpose, 7 cases of SANT with typical histopathological features were retrieved. First, the presence of CTNNB1 exon 3 alterations was examined with a recently described immunohistochemistry-based method. Then, the findings were confirmed with polymerase chain reaction (PCR), reverse transcription PCR (RT-PCR), and Sanger sequencing. In all cases, immunochemistry of ß-catenin gave a staining pattern that was suggestive of exon 3 alteration; however, no missense mutations were found in any case at the CTNNB1 exon 3 hotspot region. Subsequently, we screened for large interstitial deletions of CTNNB1 exon 3 which revealed short PCR products in three cases. Sequencing confirmed that these cases had large interstitial deletions, resulting in loss of the entire exon 3 of CTNNB1. In the remaining four cases, loss of exon 3 was documented at the cDNA level, although genomic deletion was not identified. These results demonstrate that loss of CTNNB1 exon 3 and stabilization of ß-catenin with activation of Wnt signaling pathway might have a significant role in the pathogenesis of SANT. Through this study, we provided important evidence for the neoplastic nature and pathogenesis of this disorder.

Blastic Plasmacytoid Dendritic Cell Neoplasm: Single Center Experience on a Rare Hematological Malignancy.

PURPOSE: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and poor prognostic hematological malignancy. There is still no standard treatment established for BPDCN patients. We aim to summarize the main clinical, biological features and treatment of 9 BPDCN patients. METHODS: Nine patients with BPDCN who had been diagnosed between July 2008 and December 2018 in Ankara University School of Medicine, were retrospectively evaluated. RESULTS: All patients (n = 9) were male, median age was 64 (21-80). Five patients (55.6%) had bone marrow infiltration, 5 patients (55.6%) cutaneous lesions, 6 patients (66.7%) lymph node involvement, 2 patients (22.2%) central nervous system involvement and 2 patients (22.2%) spleen involvement at time of diagnosis. Complex karyotype was observed in 2 patients. CHOP was given to 5 patients (55.6%), hyper-CVAD to 2 patients (22.2%), fludarabine, cyclophosphamide and mitoxantrone to 1 patient (11.1%) and cyclophosphamide, etoposide, methylprednisolone to 1 patient (11.1%) as first line chemotherapy. Four patients (44.4%) underwent allogeneic hematopoietic stem cell transplantation (AHSCT) in complete remission (CR) 1. Venetoclax was given to a transplant ineligible patient who had skin and lymph node involvement, with the off-label use. The median follow-up time was 15.9 months (3-48.6 months). Estimated median overall survival was 15.9 + 1.6 (95% CI 12.7-19.1) months. CONCLUSION: Intensive induction therapies followed by AHSCT in CR seems to be best approaches for patients with BPDCN. Thus, more effective treatment strategies particularly targeted therapies should be warranted to improve the survival of patients with this rare disease.

A child with myelodysplastic syndrome with hypocellular fibrosis.

A 9-year-old girl with intractable anemia, rare mucocutaneous bleeding, and pallor was presented. Hemoglobin was 49 g/L; reticulocyte 0.79%, mean corpuscular volume 81 fL, platelet 37×109/L; white blood cell count 3.2×109/L with dysmorphic cells in peripheric blood. Further evaluation revealed 10% cellularity with grade IV reticulin fibrosis, immature, and/or dysplastic hematopoietic cells without sideroblasts, or blast increase in biopsy, Monosomy 8 was found in bone marrow aspiration material using FISH. Vitamin B12, folic acid, hemoglobin electrophoresis, immunoglobulin levels, CD55, CD59, complement 3, 4, abdominal ultrasonography, chest x-ray were normal; diepoxybutane, acid ham, sucrose lysis tests, viral serologies, antinuclear antibody, anti DNA were negative. On diagnosis of "Myelodysplastic Syndrome-refractory cytopenia with hypocellular fibrosis," she received a successful allogeneic BM transplantation from her full matched sibling.

Bronchoscopic electrocautery therapy of a solitary endobronchial extramedullary plasmacytoma.

Extramedullary plasmacytomas are rare tumors. In majority of cases tumors arise in the head and neck region and endobronchial localization is extremely rare. The treatment is usually resection alone or combination of surgery with radiotherapy. Herein we present a case of solitary endobronchial plasmacytoma which was resected with bronchoscopic electrocautery, because of extremely rare occurrence of solitary endobronchial plasmacytoma and also the successful outcome of bronchoscopic electrocautery therapy.

Enzyme replacement therapy in type 1 Gaucher disease and a review of the literature.

Gaucher disease (GD) is the most common lysosomal storage disorder. Deficiency of the lysosomal enzyme glucocerebrosidase results in the intracellular accumulation of undegraded substrates in the spleen, liver and bone marrow. Enzyme replacement therapy (ERT) is a standard approach for type 1 GD. Here, we present an adult patient with hematological disorders due to type 1 GD, who markedly improved with ERT.

WHO 2016 Definition of Chronic Myeloid Leukemia and Tyrosine Kinase Inhibitors

Philadelphia (Ph*)/BCR-ABL1-positive chronic myeloid leukemia (CML) is considered as a chronic life-long disease, which could be manageable with tyrosine kinase inhibitor (TKI) drugs. The aim of TKI drug treatment is to provide age- and sex-matched duration of life in a given patient with CML. Personalized CML treatment with TKI drugs is the key strategy. Individual treatment approach includes the harmonization of CML disease characteristics, clinical experience, and best available clinical evidence. Specific CML disease characteristics in a given patient include; CML disease risk, comorbidities, molecular profile, compliance, lifestyle, and drug off-target risk profile. CML research evidence includes; randomized clinical trials indicating the data on the efficacy, safety, tolerability, toxicity, possible long-term adverse events, and pharmacoeconomy of TKIs. Clinical and physician experience includes TKI availability, TKI reimbursability, drug experience, adherence, and BCR-ABL1 monitorization facilities. The key decision of choosing a TKI of choosing TKIs for CML should be made via the consideration of these variables. The aim of this paper is to outline the latest 2016 World Health Organization definition of CML and its proper management with TKI-class drugs.

Simultaneous occurrence of Kaposi's sarcoma and nodular lymphocyte predominant subtype of Hodgkin's lymphoma in the same lymph node.

Many cases have been established with coexisting Kaposi's sarcoma (KS) and classical Hodgkin's Lymphoma (C-HL) in the same lymph node. But composite presentation of KS and Nodular Lymphocyte Predominant subtype of Hodgkin's lymphoma (NLPHL) in the same lymph node has not been described yet. KS is related to immunodeficiency most frequently due to human immunodeficiency virus (HIV) infection or immunosupression by other reasons. Our case presented here was not related to any immunodeficiency status. Besides of being the first case of composite KS and NLPHL in the same lymph node, it was also unusual with the indolent behaviour of the NLPHL without any therapy for 8 years follow up and primary lymph node presentation of KS without cutaneous involvement.

Immunohistochemical Biomarkers in Diagnosis of Hematolymphoid Neoplasms of Endocrine Organs.

The hematolymphoid infiltrations are challenging lesions in endocrine organs and tissues. The fourth edition of WHO classification of tumors of endocrine organs and the fourth edition of WHO classification of tumors of hematopoietic and lymphoid tissues are recently published. The updates in both fields include some new disease descriptions and prognostic markers. Our aim in this review article is to give practical diagnostic information about the most frequently seen hematolymphoid involvements of the pituitary gland, thyroid, and adrenal tissue. We designed the text in the order of organs and the contents according to the disease frequency. The pituitary gland and cellar region are the most frequently involved with Langerhans cell histiocytosis. Although it is very rare, Erdheim-Chester disease has recently been included in the classification and still needs more clear diagnostic definitions. Lymphoproliferative thyroid lesions and presentations create diagnostic problems for the pathologists. IGG4-related disease and its relation with thyroiditis is a new concept. There are many unknowns on pathobiology of the disease spectrum and discussion on defined diagnostic criteria of the IGG4-related thyroid diseases. The overlapping features of thyroiditis and primary thyroid lymphomas also create diagnostic difficulties. The frequently recognized primary hematolymphoid lesions of the endocrine organs may not be difficult to diagnose since they are expected lesions. The secondary involvement of hematolymphoid neoplasia may be more difficult to diagnose for an endocrine pathologist. In this review article, we aim to give brief description of the diseases and practical diagnostic approach by using optimum markers guided by the latest WHO classifications.