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Absolute monocyte/lymphocyte count prognostic score is independent of immunohistochemically determined cell of origin in predicting survival in diffuse large B-cell lymphoma
(Informa Healthcare, 2012) Porrata, Luis F.; Ristow, Kay; Habermann, Thomas M.; Ozsan, Nazan; Dogan, Ahmet; Macon, William; Colgan, Joseph P.; Witzig, Thomas E.; Inwards, David J.; Ansell, Stephen M.; Micallef, Ivana N.; Johnston, Patrick B.; Nowakowski, Grzegorz S.; Thompson, Carrie; Markovic, Svetomir N.
The absolute monocyte/lymphocyte count prognostic score (AMC/ALC score) has not been directly compared with the cell of origin (COO) to predict overall survival (OS) and progression-free survival (PFS) in diffuse large B-cell lymphoma (DLBCL). Thus, we retrospectively examined a new cohort of 99 patients with DLBCL treated from 2008 to 2010, (1) to validate whether AMC/ALC score affects survival, (2) to investigate whether AMC/ALC score is independent of COO to predict survival and (3) to assess whether AMC/ALC score can further stratify clinical outcomes by COO. By univariate analysis, the AMC/ALC score was a predictor for OS and PFS. On multivariate analysis performed including the COO and the International Prognostic Index, AMC/ALC score remained an independent predictor for OS and PFS. The AMC/ALC score was able to further stratify DLBCL clinical outcomes by COO. The AMC/ALC score was independent of COO and added to its ability to identify patients with high-risk disease.
Allogeneic hematopoietic stem cell transplantation for Blastic Plazmositoid Dentritic Cell Neoplazm: Is The Best Treatment Option ?
(Nature Publishing Group, 2018) Bulbul, Hale; Hekimgil, Mine; Ozsan, Nazan; Tobu, Mahmut
[No Abstract Available]
Anti-Yo Antibody-mediated Paraneoplastic Cerebellar Degeneration in a Female Patient with Pleural Malignant Mesothelioma
(Oxford Univ Press, 2013) Tanriverdi, Ozgur; Meydan, Nezih; Barutca, Sabri; Ozsan, Nazan; Gurel, Duygu; Veral, Ali
Paraneoplastic cerebellar degeneration is a rare non-metastatic complication of malignancies. It presents with acute or subacute onset of ataxia, dysarthria and intention tremor. Paraneoplastic cerebellar degeneration is most commonly associated with malignancies of the ovary, breast and lung. The anti-Yo (anti-Purkinje cells) antibodies that specifically damage the Purkinje cells of the cerebellum are found in the serum and cerebrospinal fluid. Anti-Yo-related paraneoplastic cerebellar degeneration is most commonly found in women with gynecological and breast cancers, but it is reported in other malignancies. Patients with paraneoplastic syndromes most often present with neurologic symptoms before an underlying cancer is detected. We report a case of anti-Yo-related paraneoplastic cerebellar degeneration associated with pleural malignant mesothelioma in a 51-year-old female patient. She presented to our department with a 2-week history after the last chemotherapy of progressive diziness related to head movement, nausea, vomiting, ataxia and unsteady gait. A western blot assay was negative for anti-Hu, anti-Ri, anti-Ma2, anti-CV2 and anti-amphiphysin paraneoplastic antibody markers but positive for anti-Yo. In conclusion, we report a case of paraneoplastic cerebellar degeneration in a patient with pleural malignant mesothelioma because of the rarity of this neurologic presentation after the diagnosis of malignant mesothelioma and of the association with anti-Yo antibodies.
Bilateral Lacrimal Gland Lymphoma in Sjogren Syndrome
(Hindawi Ltd, 2016) Palamar, Melis; Ozsan, Nazan; Sahin, Fahri
A 31-year-old female with Primary Sjogren Syndrome (pSS) presented with bilateral puffiness around the eye for 3 years. The lacrimal glands were hypertrophic and edematous bilaterally. Schirmer 1 score was 2 and 1 mm and tear-film break-up time was 3 and 4 seconds, in the right and the left eyes, respectively. An incisional biopsy from the left lacrimal gland revealed diffuse and intense CD20, CD5, and bcl-2 positivity with negative cyclin D1 and CD23 which supported lymphoma. Upon haematology consultation extranodal marginal zone lymphoma diagnosis was made. CHOP (cyclophosphamide, doxorubicin, vincristine, and methyl prednisolone) treatment was initiated. In conclusion, pSS is a well known autoimmune disease in which increased rate of lymphoma is present. Early detection with histopathologic confirmation and multidisciplinary approach with ophthalmology, rheumatology, and haematology are mandatory in these patients.
A BRIEF OVERVIEW TO PEDIATRIC GRAY ZONE LYMPHOMAS
(Wiley, 2022) Ataseven, Eda; Ozek, Gulcihan; Ozsan, Nazan; Kamer, Serra; Anacak, Yavuz; Aksoylar, Serap; Kantar, Mehmet
[No Abstract Available]
Castleman's Disease: The Experience Over 17 Years
(Cig Media Group, Lp, 2018) Saydam, Güray; Atilla, Fatos Dilan; Demir, Derya; Bulbul, Hale; Davulcu, Eren Arslan; Ulusoy, Yusuf; Hekimgil, Mine; Ozsan, Nazan; Sahin, Fahri
Clinical Features and Outcomes of Solitary Plasmacytomas: Single-Center Experience from Turkey
(Cig Media Group, Lp, 2018) Saydam, Güray; Ulusoy, Yusuf; Davulcu, Eren Arslan; Soyer, Nur; Kamer, Emine Serra; Ozsan, Nazan; Hekimgil, Mine; Sahin, Fahri
Clinicopathologic and Genetic Characterization of Follicular Lymphomas Presenting in the Ovary Reveals 2 Distinct Subgroups
(Lippincott Williams & Wilkins, 2011) Ozsan, Nazan; Bedke, Brent J.; Law, Mark E.; Inwards, David J.; Ketterling, Rhett P.; Knudson, Ryan A.; Keeney, Gary L.; Dogan, Ahmet; Feldman, Andrew L.
Most lymphomas arising in the ovary are diffuse large B-cell or Burkitt lymphomas. Follicular lymphomas of the ovary are rare, and their clinicopathologic features are incompletely understood. We investigated clinical, morphologic, immuno-phenotypic, and genetic features of follicular lymphomas initially diagnosed in the ovary in 16 women. We performed immunohistochemistry for CD20, CD3, CD10, BCL6, IRF4/MUM1, and BCL2 and interphase fluorescence in situ hybridization for translocations involving BCL2, BCL6, and IRF4. Clustering was performed on the basis of clinicopathologic and genetic variables using Cluster 3.0. Ages ranged from 42 to 73 years. Unsupervised hierarchical clustering analysis revealed 2 distinct groups of patients. One group (group A) included 7 cases, which were negative or weakly positive for BCL2 protein and lacked IGH@/BCL2 translocations (6 cases evaluable). Four patients were of grade 3A, and 3 patients were of grade 2. Four had stage IE disease with unilateral ovarian involvement (subgroup A(1)), and the stage was unknown in 3 patients (subgroup A(2)). The second group (group B) included 9 cases of low histologic grade, which strongly expressed BCL2 protein and had IGH@/BCL2 translocations (7 cases evaluable). Six patients had stage III/IV disease, 2 had stage II disease, and the stage was unknown in 1 patient. Although follow-up intervals were limited, patients with higher-grade/ low-stage disease tended to have favorable outcomes. These data indicate 2 distinct types of follicular lymphomas presenting in the ovary: a low-grade/high-stage/BCL2-positive group and a higher-grade/low-stage/BCL2-negative group. This latter group likely has distinct biological and immunologic characteristics, as has been suggested for higher-grade/ low-stage follicular lymphomas presenting at other extranodal sites.
Complex karyotype with double Philadelphia chromosome and T315I mutation results in blastic phase and extensive extramedullary infiltration in a chronic myeloid leukemia patient
(Elsevier Science Inc, 2022) Davulcu, Eren Arslan; Pekerbas, Mert; Karaca, Emin; Durmaz, Burak; Ozsan, Nazan; Akin, Haluk; Saydam, Guray
Chronic myeloid leukemia (CML) is a common hematological malignancy originating from bone marrow stem cells. Chromosomal abnormalities can be seen in almost all cases, the most known anomaly being Philadelphia (Ph) chromosome, a derivative chromosome resulting from a translocation between 9. and 22. chromosome. Other chromosomal abnormalities may be present in 10% of patients at diagnosis, al-though they emerge frequently during the acute transformation and can be associated with unfavorable significance. Also, point mutations like T315I in BCR-ABL fusion gene may arise during the course of the disease and thereby cause tyrosine kinase inhibitors (TKI) resistance. Here, we report a BCR-ABL positive CML patient who was followed for 6 years in major molecular response (MMR), complete cytogenetic response (CCR), and complete hematological response (CHR). He had a sudden loss of hematological, cy-togenetic, and molecular response with a very aggressive blastic course and extensive extramedullary infiltration, with T315I mutation, complex translocations, an extra Ph chromosome, and additional chro-mosomes. The patient who received intensive cytotoxic chemotherapy together with ponatinib treatment, which is effective for the T315I mutation, never went into remission, and there was no chance of trans-plantation because a suitable donor for HLA could not be found. Although these findings are not very rare individually, coexistence of complex karyotype and T315I mutation is not frequent and complicates clinical management. Our patient is the first case in literature with all disclosed findings together and indicates the importance of early detection of these chromosomal and molecular abnormalities.(c) 2022 Elsevier Inc. All rights reserved.
CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis
(Springer, 2013) Charbonneau, Bridget; Wang, Alice H.; Maurer, Matthew J.; Asmann, Yan W.; Zent, Clive S.; Link, Brian K.; Ansell, Stephen M.; Weiner, George J.; Ozsan, Nazan; Feldman, Andrew L.; Witzig, Thomas E.; Cunningham, Julie M.; Dogan, Ahmet; Habermann, Thomas M.; Slager, Susan L.; Novak, Anne J.; Cerhan, James R.
CXCR5 [chemokine (C-X-C motif) receptor 5; also known as Burkitt lymphoma receptor 1 (BCR1)] is expressed on mature B-cells, subsets of CD4(+) and CD8(+) T-cells, and skin-derived migratory dendritic cells. Together with its ligand, CXCL13, CXCR5 is involved in guiding B-cells into the B-cell zones of secondary lymphoid organs as well as T-cell migration. This study evaluated the role of common germline genetic variation in CXCR5 in the risk and prognosis of non-Hodgkin lymphoma (NHL) using a clinic-based study of 1,521 controls and 2,694 NHL cases including 710 chronic lymphocytic leukemia/small lymphocytic lymphoma, 586 diffuse large B-cell lymphoma (DLBCL), 588 follicular lymphoma (FL), 137 mantle cell lymphoma (MCL), 230 marginal zone lymphoma (MZL), and 158 peripheral T-cell lymphoma (PTCL). Of the ten CXCR5 tag SNPs in our study, five were associated with risk of NHL, with rs1790192 having the strongest association (OR 1.19, 95 % CI 1.08-1.30; p = 0.0003). This SNP was most strongly associated with the risk of FL (OR 1.44, 95 % CI 1.25-1.66; p = 3.1 x 10(-7)), with a lower degree of association with DLBCL (OR 1.16, 95 % CI 1.01-1.33; p = 0.04) and PTCL (OR 1.29, 95 % CI 1.02-1.64; p = 0.04) but no association with the risk of MCL or MZL. For FL patients that were observed as initial disease management, the number of minor alleles of rs1790192 was associated with better event-free survival (HR 0.64; 95 % CI 0.47-0.87; p = 0.004). These results provide additional evidence for a role of host genetic variation in CXCR5 in lymphomagenesis, particularly for FL.
Determination of apoptosis, proliferation status and O-6-methylguanine DNA methyltransferase methylation profiles in different immunophenotypic profiles of diffuse large B-cell lymphoma
(Galenos Yayincilik, 2011) Sen Turk, Nilay; Ozsan, Nazan; Caner, Vildan; Karagenc, Nedim; Duzcan, Fusun; Duzcan, Ender; Hekimgil, Mine
Our aim was to investigate the expression of apoptosis-associated proteins (bcl-2, bcl-xl, bax, bak, bid), apoptotic index (AI) and proliferation index (PI) in germinal center B-cell-like immunophenotypic profile (GCB) and non-GCB of diffuse large B-cell lymphoma (DLBCL). Materials and Methods: The methylation status of the promoter region of O-6-methylguanine-DNA yerine O-6-methylguanine-DNA methyltransferase (MGMT) gene and its relation with immunophenotypic differentiation of DLBCLs were also investigated. 101 cases were classified as GCB (29 cases) or non-GCB (72 cases). Apoptosis-associated proteins and PI were determined by IHC, and TUNEL method was used to determine AI. MGMT methylation analysis was performed by real-time PCR. Results: The PI was significantly higher in GCB compared with non-GCB (p=0.011). Percentage of cells stained with bcl-6 was positively correlated with the percentage of cells expressing bcl-2 (p=0.023), AI (p=0.006) and PI (p<0.001), while a significant negative correlation was observed with the percentage of cells expressing bax (p=0.027). The percentage of cells stained with MUM1 showed a significantly positive correlation with the percentage of cells expressing bcl-xl (p=0.003), bid (p=0.002), AI (p<0.001), and PI (p=0.001). MGMT methylation analysis was performed in 95 samples, and methylated profile was found in 31 cases (32.6%). GCB was found in 6 cases (22.2%) and non-GCB was determined in 25 cases (36.8%) out of 31 with MGMT methylated samples. There was no significant association between MGMT methylation status and immunophenotypic profiles (p=0.173). Conclusion: These results suggest that bcl-6 protein expression may be responsible for the high PI in GCB. Additionally, we found that apoptosis-associated proteins were not significantly associated with immunophenotypic profiles. (Turk J Hematol 2011; 28: 15-26)
Diffuse Large B-Cell Lymphoma Arising in Warthin's Tumor: Case Study and Review of the Literature
(Korean Society Pathologists, 2013) Ozkok, Guliz; Tasli, Funda; Ozsan, Nazan; Ozturk, Rafet; Postaci, Hakan
Warthin's tumor is the second most common type of salivary gland tumor. Microscopically, Warthin's tumor displays a proliferative epithelial component and lymphoid stroma. Carcinomas arising from the epithelial component are well known, but malignant transformations of the lymphoid stroma are rare. When they do occur, they are most commonly B-cell type non-Hodgkin lymphomas. A 60-year-old male patient underwent surgical resection of a parotid mass. After superficial parotidectomy, microscopic examination indicated that the tumor was of epithelial components with basaloid and oncocytic columns of cells neighboring lymphoid components. In addition to the lymphoid follicles with distinct germinal centers, there were large, bizarre and extremely atypical neoplastic cells seen in the lymphoid component. Large neoplastic cells were diffusely CD20 and CD30 positive. The patient was diagnosed with "Warthin's tumor and diffuse large B-cell lymphoma with expression of CD30." The histopathologic and clinical features are discussed along with a review of the literature.
Epstein-Barr virus (EBV) positive diffuse large B cell lymphoma of the elderly-Experience of a single center from Turkey
(Elsevier Gmbh, Urban & Fischer Verlag, 2013) Ozsan, Nazan; Cagirgan, Seckin; Saydam, Güray; Gunes, Ajda; Hekimgil, Mine
In the 2008 WHO lymphoma classification, 'EBV-positive diffuse large B cell lymphoma (DLBCL) of the elderly is included as a new provisional entity. We aimed to evaluate the morphological, immunophenotypic, and clinical characteristics of the cases diagnosed as 'EBV-positive DLBCL of the elderly' in our center and compared them with the 'EBV-negative DLBCL' patients older than 50 years of age. EBV status was detected by Epstein-Barr early RNA (EBER) in situ hybridization analysis. By immunohistochemistry, a panel of antibodies for CD10, Bcl-2, Bcl-6, IRF4/MUM1, CD30, and Ki67 was performed. Out of 149 DLBCL patients older than 50 years, without any known history of immunodeficiency or prior lymphoma, eight patients who fulfill the criteria were re-evaluated. Five patients were male and three were female, with a median age of 67.6 years. Four patients presented with nodal involvement; others presented with bone and soft tissue, bone marrow, and spleen infiltrations. Five cases revealed predominantly monomorphic morphology, one also contained focal areas consistent with polymorphous subtype; and three patients revealed a polymorphous infiltrate. When classified according to 'Hans criteria', five were non-GCB, and three were of the GCB cell phenotype. All cases with polymorphous morphology were revealed to be of the non-GCB cell phenotype, and all expressed IRF4/MUM1. Two patients died with disease, four patients are alive and in complete remission following R-CHOP therapy, and two patients have just recently been diagnosed. When compared with the EBV-negative group, there are no reliable morphological and immunohistochemical features indicating EBV positivity. Therefore, EBER in situ hybridization analysis is necessary to identify 'EBV-positive DLBCL of the elderly'. Further studies are needed to fully understand the details of this disease, which can lead to new treatment modalities. (C) 2013 Elsevier GmbH. All rights reserved.
Epstein-Barr virus (EBV) positive diffuse large B cell lymphoma of the elderly-Experience of a single center from Turkey
(Elsevier Gmbh, Urban & Fischer Verlag, 2013) Ozsan, Nazan; Cagirgan, Seckin; Saydam, Güray; Gunes, Ajda; Hekimgil, Mine
In the 2008 WHO lymphoma classification, 'EBV-positive diffuse large B cell lymphoma (DLBCL) of the elderly is included as a new provisional entity. We aimed to evaluate the morphological, immunophenotypic, and clinical characteristics of the cases diagnosed as 'EBV-positive DLBCL of the elderly' in our center and compared them with the 'EBV-negative DLBCL' patients older than 50 years of age. EBV status was detected by Epstein-Barr early RNA (EBER) in situ hybridization analysis. By immunohistochemistry, a panel of antibodies for CD10, Bcl-2, Bcl-6, IRF4/MUM1, CD30, and Ki67 was performed. Out of 149 DLBCL patients older than 50 years, without any known history of immunodeficiency or prior lymphoma, eight patients who fulfill the criteria were re-evaluated. Five patients were male and three were female, with a median age of 67.6 years. Four patients presented with nodal involvement; others presented with bone and soft tissue, bone marrow, and spleen infiltrations. Five cases revealed predominantly monomorphic morphology, one also contained focal areas consistent with polymorphous subtype; and three patients revealed a polymorphous infiltrate. When classified according to 'Hans criteria', five were non-GCB, and three were of the GCB cell phenotype. All cases with polymorphous morphology were revealed to be of the non-GCB cell phenotype, and all expressed IRF4/MUM1. Two patients died with disease, four patients are alive and in complete remission following R-CHOP therapy, and two patients have just recently been diagnosed. When compared with the EBV-negative group, there are no reliable morphological and immunohistochemical features indicating EBV positivity. Therefore, EBER in situ hybridization analysis is necessary to identify 'EBV-positive DLBCL of the elderly'. Further studies are needed to fully understand the details of this disease, which can lead to new treatment modalities. (C) 2013 Elsevier GmbH. All rights reserved.
Epstein-Barr virus-related lymphoproliferative disorders in T-cell repleted haploidentical transplantation with post-transplant cyclophosphamide
(Springer Japan Kk, 2022) Uygun, Vedat; Ozsan, Nazan; Daloglu, Hayriye; Ozturkmen, Seda; Yalcin, Koray; Karasu, Gulsun; Yesilipek, Akif
EBV-associated lymphoproliferative disorders (LPDs) are common in hematopoietic stem cell transplantation (HSCT) with T-cell-depleted grafts, but are extremely rare in HSCT patients with T-cell-replete grafts with post-transplant cyclophosphamide (PTCy). Here we present the cases of two pediatric patients who developed EBV-related LPD after T-cell-replete haplo-HSCT with PTCy. One of these is the first reported case of EBV-positive mucocutaneous ulcer (EBVMCU) developing after PTCy. EBV-related diseases are rare in T-cell-replete haplo-HSCT patients with PTCy. However, in patients with risk factors, it is reasonable to screen for EBV viremia for LPD.
Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP
(Amer Soc Hematology, 2012) Gupta, Mamta; Maurer, Matthew J.; Wellik, Linda E.; Law, Mark E.; Han, Jing Jing; Ozsan, Nazan; Micallef, Ivana N.; Dogan, Ahmet; Witzig, Thomas E.
STAT3 regulates cell growth by upregulating downstream targets, such as Myc. The frequency of phosphorylated STAT3 (pSTAT3) and Myc expression and their prognostic relevance is unknown within diffuse large B-cell lymphoma (DLBCL) germinal center B-cell (GCB) and non-GCB subtypes. pSTAT3 and Myc were studied by immunohistochemistry (IHC) on tumors from 40 DLBCL patients uniformly treated on a clinical trial of epratuzumab/rituximab-CHOP. A total of 35% of cases were pSTAT3-positive, and pSTAT3 positivity was more frequent in the non-GCB (P = .06) type but did not correlate with event-free survival (EFS). Myc expression was observed in 50% of cases and was more frequent in non-GCB type (P = .07). Myc-positive cases had inferior EFS in all patients, including the GCB and pSTAT3-positive cases, were more likely to express Myc (P = .06). Myc translocations involving the major breakpoint regions were found in 10% (3 of 29) of cases, and all 3 cases were GCB and had an inferior EFS (P = .09). pSTAT3, but not Myc expression, was correlated with elevated pretreatment serum cytokines, such as IL-10 (P = .05), G-CSF (P = .03), and TNF-alpha (P = .04). pSTAT3 IHC in DLBCL tumors has the potential to identify patients for STAT3 pathway-directed therapy; Myc IHC is a potential marker for inferior EFS in GCB patients. (Blood. 2012;120(22):4400-4406)
Extramedullary Relapse in a CML Patient after Allogeneic Stem Cell Transplantation
(Hindawi Ltd, 2017) Yilmaz, Asu Fergun; Soyer, Nur; Ozsan, Nazan; Cagirgan, Seckin; Gunes, Ajda; Comert, Melda; Sahin, Fahri; Saydam, Güray; Gunel, Nur Selvi; Vural, Filiz
Myeloid or granulocytic sarcoma (GS) is a tumoral lesion consisting of immature granulocytic cells. It is a rare entity during the course of CML patients especially after allogeneic stem cell transplantation (SCT). Relapse without bone marrow involvement is much rarer. We report a case of CML patient who relapsed with isolated granulocytic sarcoma after allogeneic SCT during cytogenetic and molecular remission. 28-year-old male was diagnosed as CML and allogeneic SCT was performed because of refractory disease to tyrosine kinase inhibitors. Complete cytogenetic and molecular response was achieved after allogeneic SCT followed by dasatinib treatment. Approximately 5 years after the transplantation, very rapidly progressive lesion was documented and diagnosed as GS although he was at molecular and cytogenetic remission. The patient died during chemotherapy due to sepsis. GS relapse after allogeneic SCT is a very rare type of relapse in CML patients with molecular and cytogenetic remission. Since it is a very aggressive disease with a poor prognosis, combined chemoradiotherapies with other possible options like DLI or second allogeneic SCT should be considered as soon as the diagnosis is confirmed.
Extranasal extranodal NK/T cell lymphoma: A post-transplantation lymphoproliferative disease
(Wiley, 2019) Acar, Ayda; Nurlu, Ertan; Sokmen, Nur; Ozsan, Nazan; Davulcu, Eren A.; Ceylan, Can
Extranodal NK/T cell lymphoma (ENKTL) is a rare form of non-Hodgkin lymphoma. It mostly occurs in the upper respiratory tract. Cutaneous involvement can be seen among the extranasal ENKTLs. After solid organ and haematopoietic stem cell transplantation, post-transplantation lymphoproliferative disease because of immunosuppressive therapy is usually B cell-derived; T and NK/T cell-derived disease is rarely seen. A 43-year-old female patient who had renal transplantation 14 years ago presented with cutaneous ulceration and subcutaneous nodules located in the abdomen. The patient was diagnosed with ENKTL, nasal type. Although it is rare, ENKTL nasal type is a lymphoproliferative disease that should be considered in the differential diagnosis of ulcerated cutaneous tumoural lesions.
The first report of colonic involvement of angioimmunoblastic T-cell lymphoma
(Aves, 2020) Turan, Ilker; Ozsan, Nazan; Dojanavsargil, Basak; Davulcu, Eren ArsIan; Bulbul, Hale
[No abstract available]
Frontal Lobe Like Syndrome Due To Bee Sting
(Journal Neurological Sciences, 2014) Gokmen, Nihal Mete; Evyapan Akkus, Dilek; Gulluoglu, Halil; Jara, Maria; Sanchez, Laura; Ozsan, Nazan; Donmez, Ayhan; Escribano, Luis; Gokmen, Erhan
A 34 year-old male beekeeper experienced flushing, breathing difficulty and loss of consciousness five minutes after he got stung by a honeybee. He was admitted to a local emergency room with hypotension and a phyliform pulse. After a 24-hour period of unresponsiveness, the patient gained consciousness and was discharged home. Two weeks later however, the patient presented with slowing of speech, personality and behavioral changes and difficulty in resolving personal needs such as dressing. Neuropsychological assessment revealed deficits in attention, concentration, executive function, recall memory, organization and coordination and slurred speech. Cranial MRI revealed marked symmetrical hyperintense lesions involving bilateral lentiform and caudate nuclei. Skin prick tests to hymenoptera species were negative. Specific IgE levels were also undetectable. The patient's baseline tryptase level was 49 ng/mL (normal <14.1 ng/ml). Bone marrow biopsy showed dense compact mast cell aggregates in CD117 (c-kit) and tryptase stained sections. Co-expression of CD25 and CD2 were identified on mast cells by flow cytometry. An activating somatic codon Asp816 -> Val KIT mutation was detected in mast cells but not in neutrophils. Based on these findings, diagnosis of systemic mastocytosis was made. This patient represents the first case in English literature who was diagnosed with sytemic mastocytosis and frontal lobe syndrome. Frontal lobe dysfunction may emerge with bilateral basal ganglia lesions. Mast cell degranulation has been documented to enhance vascular permeability and to regulate blood-brain barrier permeability. Besides probable hypoxic encephalopathy, the increased tendency for mast cells to undergo spontaneous degranulation can be explanatory for vasogenic edema in systemic mastocytosis.

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