Deniz Cetiner

Extramedullary plasmacytomas of the thyroid and pericardium as initial presentation of multiple myeloma

Dear Editor, Multiple myeloma belongs to a group of diseases known as the plasma cell dyscrasias, in which an uncontrolled proliferation of plasma cells elaborates a specific immunoglobulin molecule [1]. Extramedullary plasmacytoma (EMP), a malignant neoplasm of the soft tissues composed of plasma cells, may occur either as a solitary plasma-cell tumor (primary EMP) or as a manifestation of multiple myeloma (secondary EMP) [2]. Extramedullary plasmacytoma is an uncommon localized plasma cell malignancy representing 3% of plasma cell neoplasms and less than 1% of all head and neck malignancies. Reports of tumors occurring elsewhere are largely confined to single cases. The thyroid is one of the rarest sites of extramedullary plasmacytoma [3]. Multiple myeloma involving the thyroid gland is exceedingly rare. Extramedullary localization at diagnosis or during the course of multiple myeloma is a rare event with a very aggressive course. The chest may be involved by skeletal osteolytic lesions, pathological fractures, and plasmacytomas. Pleural and pericardial abnormalities can be observed in this condition but are rarely related to myelomatous effusions [4]. We herein present an unusual appearance of multiple myeloma in an extramedullary location: diffuse enlargement of the thyroid gland, pericardial mass, and pleural and pericardial effusion. A 76-year-old woman presented to the emergency department with increasing hoarseness, progressive difficulty breathing and with a 3-month history of a lump in the neck of increasing size. She experienced some dysphasia. There were no toxic symptoms. Examination showed a massive, diffusely nodular, painless enlargement of both lobes of the thyroid. At this time, the patient had no other known lesions or masses. There was no cervical lymphadenopathy. The hemoglobin was 9.5 g per 100 ml, the white blood cell count 2,300 per cubic millimeter, and the sedimentation rate was 18 mm/h. A chest radiograph showed a widened cardiac silhouette and bilateral moderate pleural effusion. Radiographs of the thoracic inlet showed some tracheal deviation and compression. A skeletal survey was normal. Upon computed tomography (CT) scan of the neck, a mass, centered on the left lobe and isthmus of thyroid, extended to the right inferior thyroid lobe and upper mediastinum and was measured 5.6×8.2×6 cm in largest dimension. The trachea was shifted to the right and posterior in spite of the mass, and the airway lumen was slight narrowed. Also, the mass encircled the right and left common carotid arteries over 180° and compressed the left jugular vein. An ultrasoundguided fine-needle aspiration (FNA) was performed on the thyroid gland. Smears from the thyroid FNA were highly cellular, showing predominantly discohesive, plasmacytoid cells with frequent binucleation and rare multinucleation. Biopsy of the thyroid revealed diffuse infiltration with multiple myeloma plasma cells. Immunohistochemical studies were positive for epithelial membrane antigen (EMA) and lambda and negative for kappa. The tumor showed Ki-67 proliferation index of 90%. Bone marrow biopsy was hyper cellular, with 30% plasma cells in bone marrow aspiration smears. Immunohistochemically, these Ann Hematol (2008) 87:853–854 DOI 10.1007/s00277-008-0484-x

Unusual extramedullary recurrences and breast relapse despite hepatic GVHD after allografting in Ph+-ALL

Abstract Extramedullary recurrences with or without bone marrow involvement are reported in up to a half of leukemic relapses after BMT. Our report describes a case of an extramedullary recurrence and breast relapse after second-allografting in a female patient with Ph+-acute lymphoblastic leukemia (ALL), occurring when there was active hepatic GHVD. This case illustrates the complex relationship between graft-versus-host disease (GVHD) and graft-versus-leukemia since she had no evidence of leukemia in her marrow demonstrating 100% full-donor chimerism while she had ALL relapse in her breast.

Soluble Platelet Glycoprotein V in Distinct Disease States of Pathological Thrombopoiesis

Quantitative platelet disorders (i.e., thrombocytosis or thrombocytopenia) may also be associated with qualitative platelet alterations. Clonal thrombocythemia (CT), reactive thrombocytosis (RT), immune thrombocytopenic purpura (ITP), and thrombocytopenia of aplastic pancytopenia (AA) or infiltrative bone marrow disorders represent the major classes of pathological thrombopoiesis. Glycoprotein V may serve as an in vivo marker of platelet activation in thrombotic and hemorrhagic states. The aim of this study was to assess circulating plasma soluble platelet glycoprotein V (sGPV) concentrations in distinct disease states of pathological thrombopoiesis. The whole study group comprised 20 patients with thrombocytopenia, 32 patients with thrombocytosis and 14 healthy adults as the control group. sGPV was significantly increased in the group of thrombocytosis patients in comparison to the thrombocytopenic group and the healthy control groups. When sGPV levels were corrected according to platelet number (sGPV/tr), this ratio was very high in patients with thrombocytopenia compared to patients with thrombocytosis and the control group. Our results suggest that there is an ongoing platelet activation associated with thrombocytosis regardless of its origin is either CT or RT. Therefore, glycoprotein V system may serve to activate residual platelets in thrombocytopenia regardless of its origin is either ITP or AA.

Unchanged global fibrinolytic capacity during the course of hematopoietic stem cell transplantation.

Hemostatic changes due to vascular endothelial damage are seen during the course of hematopoietic stem cell transplantation (HSCT). The fibrinolytic response to ongoing hemostatic activation in HSCT remains to be elucidated. Global fibrinolytic capacity (GFC) is a novel method, which reflects the amount of generated D-dimer when fibrinolysis of a freeze-dried fibrin clot is stopped by introducing aprotinin. GFC is sensitive to all the factors involved in the process of fibrinolysis. The aim of this study was to serially assess GFC at certain critical time points (days −1, +7, +14, +21 prior to and following stem cell infusion) during the course of HSCT. The study group comprised 16 patients with hematological malignancies (11 women, five men; median age 32 ± 9 years) in whom HSCT had been performed. Thirty healthy adults (21 women, nine men; median age 31 ± 7 years) served as controls. In this study, global fibrinolytic response, as reflected by GFC, was unchanged despite ongoing hemostatic activation, as indicated by D-dimer, moreover GFC remained stable, despite the development of thrombocytopenia associated with HSCT prior to platelet engraftment. Our results indicate that a global fibrinolytic response was impaired as a compensatory response to endothelial activation and to other hemostatic changes seen in HSCT. Further studies in larger HSCT populations are warranted to better understand the implications of these findings.

YENİ TANILI ERİŞKİN AKUT LENFOBLASTİK LÖSEMİ HASTALARINDA TOTAL SAĞKALIMI ETKİLEYEN FAKTÖRLER

Giris: Modern kemoterapi protokolleri ile tedavi edilen akut lenfoblastik losemili (ALL) hastalarin prognozu cesitli degiskenlere baglidir. Bu risk faktorlerinin belirlenmesi remisyondan sonraki donemde tedavinin belirlenmesi icin oldukca onemlidir. Biz burada, eriskin ALL hastalarindaki klinik ozellikleri ve prognostik faktorleri belirlemeye calistik. Gerec ve yontem: Merkezimizde Ocak 2003 ile Aralik 2008 tarihleri arasinda yeni tani konulan 65 eriskin ALL hastasinin retrospektif degerlendirmesi yapilmistir. Median yas 35,6 (dagilim 16–72) ve hastalarin %70’i B-ALL, %20’si T-ALL ve %10’nu da Burkitt ALL idi. 32 hasta Hiper-CVAD, 25 hasta CALGB–8811, 3 hasta HAM (yuksek doz sitarabin + mitoksantron) ve birer hasta MOPP, St Jude Total XIII ve CHOP21 protokolleri almislardi. Bir hasta CALGB8811 protokolu alip remisyona girdigi halde karaciger toksisitesi nedeni ile tedavisine Hiper-CVAD protokolu ile devam edilmisti. Bir hastaya beyaz kure yuksekligi nedeni ile lokoferez ve hidroksiure verilmis, fakat kemoterapi baslanmadan kaybedilmisti. Bulgular: Hastalarin ortalama izlem suresi 407 (0–1706) gun idi. Sitogenetik/molekuler genetik incelemelerde 1 hastada myconcogeni ile ilgili bozukluk, 9 hastada t(9;22), 2 hastada t(4;11) bulunmustu. Hastalarin induksiyon kemoterapisine yanit oranlari; %60 (n=39) tam yanit, %32 (n=21) eks, %8 (n=5) yanitsiz hastalik olarak belirlendi. 4,6 yillik total sagkalim orani %19 idi. 4,5 yillik hastaliksiz sagkalim orani %28 idi. Sonuc: Tek degiskenli analizlerde total sagkalim ile iliskili bulunan parametreler hastaligin tipi (Burkitt, B- ya da T-ALL), ECOG performans durumu (≤1 ya da > 1) ve yas (≤ 30 ve diger) idi. Cok degiskenli analiz yapildiginda yas (p=0.018) ve ECOG performans durumu (p=0.010) total sagkalimi etkileyen degiskenler olarak bulundu.

YENİ TANILI AKUT MİYELOBLASTİK LÖSEMİ HASTALARINDA HASTALIK ÖZELLİKLERİ VE TEDAVİ SONUÇLARINI ETKİLEYEN FAKTÖRLER: TEK MERKEZ DENEYİMİ

Giris: Akut losemi tedavisi ile ilgili klinik calismalara genellikle onemli komorbiditeleri olmayan hastalar alinmaktadir. Bu nedenle literaturde bildirilen tedavi sonuclari gercek hayattaki klinik gerceklerle bagdasmayabilmektedir. Gerec ve yontem: Ocak 2003 ile Aralik 2008 tarihleri arasina unitemizde yeni tani konulan 147 AML hastasi retrospektif olarak incelenmistir. Hastalarin ortanca yasi 48 (16-85), 11 (%7,5) tanesi CBF tipi AML, 18 (%12,2) tanesi APL ve 118 (%80,3) tanesini de diger AML hastalari olusturmaktaydi. AML hastalarinin %74,8’ine idarubisin-sitarabin (3+7), %13,6’sina mitoksantronsitarabin (3+7), %2,9’una yuksek doz sitarabin-mitoksantron, %0,9’una sitarabin, %0,9’una etoposid-mitoksantron-sitarabin, %1,9’una idarubisin-sitarabin (2+5) ve %4,8’ine (akut promiyelositik losemi hastalari) modifiye AIDA kemoterapi protokolu verildi. Bulgular: Ortalama hemoglobin, beyaz kure ve trombosit degerleri sirasiyla 8,6 g/dl (3,5-14), 41 359/mm3 (600-300,000) ve 64,086/mm3 (3000-459,000) idi. Toplam 12 (%8,1) hastaya allojeneik kok hucre nakli uygulanmisti. Induksiyon tedavisi ile %52,4 tam yanit, %27,2 induksiyon esnasinda eks ve %5,4 oraninda da yanitsiz olarak bulundu. Tum hastalarin 5,9 yillik total sagkalim orani %29 ve induksiyonla remisyon saglanan hastalarda 5 yillik hastaliksiz sagkalim orani %44 idi. Sonuc: Tam yaniti etkileyen faktorler sirasiyla yas ve ECOG performans durumu bulundu. Total sagkalimi etkileyen faktorler ise yas (≤30 yas %32 sagkalim, 30-59 yas %37, ≥60 yas %13, p= 0,003), ECOG performansi (ECOG≤1 %33 sagkalim, ECOG>1 %17, p= 0,001) ve AML tipi (CBF tipi AML’de %72 sagkalim, APL hastalarinda %41, diger AML hastalarinda %24, p= 0,043) olarak bulundu. Cok degiskenli analiz yapildiginda sadece ECOG performans durumu anlamli degisken olarak bulunmustur (p=0,003).