Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106165
Burak Demir, Birol Güvenç
<div><h3>Case Report</h3><div>An 85-year-old male presented with progressive fatigue and melena over several weeks. His medical history was notable for advanced age with overall frailty but no significant comorbidities. Physical examination revealed poor general condition with pallor and mild dehydration. No palpable lymphadenopathy, hepatomegaly, or splenomegaly was detected on initial examination.</div><div>Laboratory evaluation demonstrated severe anemia (hemoglobin 8.1 g/dL, hematocrit 27%) with significant leukocytosis (20.9 × 10⁹/L) and marked monocytosis (46%). Platelet count remained normal (181 × 10⁹/L). Additional findings included hypoalbuminemia (28.5 g/L), elevated LDH (218 U/L), and moderate renal impairment (creatinine 1.23 mg/dL, eGFR 53 mL/min).</div><div>Endoscopic evaluation revealed erosive pangastritis with antral and duodenal ulcers. Colonoscopy identified a 3.5-4 cm ulcerative, polypoid mass in the cecum with additional rectal involvement prompting biopsy.</div><div>Histopathological examination of gastrointestinal biopsies confirmed mantle cell lymphoma with characteristic immunophenotype: CD20(+), Cyclin D1(+), SOX11(+), BCL2(+), and CD43(+) with negative CD3, CD5, and CD23. The Ki-67 proliferation index was 20%, indicating moderate proliferative activity.</div><div>PET-CT staging revealed extensive disease with widespread lymphadenopathy involving cervical, axillary, mediastinal, retroperitoneal, and pelvic regions. Gastrointestinal involvement showed intense FDG uptake (SUVmax 12.1) in cecum and rectum. Diffuse hepatic and splenic involvement was present along with diffuse bone marrow uptake, establishing stage IV disease.</div><div>Given the patient's advanced age (85 years), frailty, history of gastrointestinal ulceration, and moderate renal impairment, intensive chemotherapy regimens were deemed inappropriate. Treatment was initiated with rituximab monotherapy (626 mg every 28 days) with antiemetic prophylaxis. BTK inhibitor therapy was considered but deferred due to high bleeding risk given active gastrointestinal ulceration.</div><div>Supportive care included proton pump inhibitor therapy and red blood cell transfusions as needed. The patient demonstrated good tolerance to rituximab therapy with early symptomatic improvement and stabilization of hematological parameters.</div></div><div><h3>Discussion</h3><div>This case illustrates several important aspects of MCL management in elderly patients. The presentation with gastrointestinal bleeding and extensive disease is typical for MCL, which frequently involves the GI tract at diagnosis. The moderate Ki-67 proliferation index (20%) suggested less aggressive biology, supporting a less intensive treatment approach.</div><div>The decision to use rituximab monotherapy reflects the growing recognition that treatment intensity must be individualized based on patient fitness and comorbidities. While intensive regimens like hyperCVAD or Nordic protocols achieve superior outc
{"title":"Mantle Cell Lymphoma Presenting with Gastrointestinal Bleeding in an Elderly Patient: A Case of Stage IV Disease Treated with Rituximab Monotherapy","authors":"Burak Demir, Birol Güvenç","doi":"10.1016/j.htct.2025.106165","DOIUrl":"10.1016/j.htct.2025.106165","url":null,"abstract":"<div><h3>Case Report</h3><div>An 85-year-old male presented with progressive fatigue and melena over several weeks. His medical history was notable for advanced age with overall frailty but no significant comorbidities. Physical examination revealed poor general condition with pallor and mild dehydration. No palpable lymphadenopathy, hepatomegaly, or splenomegaly was detected on initial examination.</div><div>Laboratory evaluation demonstrated severe anemia (hemoglobin 8.1 g/dL, hematocrit 27%) with significant leukocytosis (20.9 × 10⁹/L) and marked monocytosis (46%). Platelet count remained normal (181 × 10⁹/L). Additional findings included hypoalbuminemia (28.5 g/L), elevated LDH (218 U/L), and moderate renal impairment (creatinine 1.23 mg/dL, eGFR 53 mL/min).</div><div>Endoscopic evaluation revealed erosive pangastritis with antral and duodenal ulcers. Colonoscopy identified a 3.5-4 cm ulcerative, polypoid mass in the cecum with additional rectal involvement prompting biopsy.</div><div>Histopathological examination of gastrointestinal biopsies confirmed mantle cell lymphoma with characteristic immunophenotype: CD20(+), Cyclin D1(+), SOX11(+), BCL2(+), and CD43(+) with negative CD3, CD5, and CD23. The Ki-67 proliferation index was 20%, indicating moderate proliferative activity.</div><div>PET-CT staging revealed extensive disease with widespread lymphadenopathy involving cervical, axillary, mediastinal, retroperitoneal, and pelvic regions. Gastrointestinal involvement showed intense FDG uptake (SUVmax 12.1) in cecum and rectum. Diffuse hepatic and splenic involvement was present along with diffuse bone marrow uptake, establishing stage IV disease.</div><div>Given the patient's advanced age (85 years), frailty, history of gastrointestinal ulceration, and moderate renal impairment, intensive chemotherapy regimens were deemed inappropriate. Treatment was initiated with rituximab monotherapy (626 mg every 28 days) with antiemetic prophylaxis. BTK inhibitor therapy was considered but deferred due to high bleeding risk given active gastrointestinal ulceration.</div><div>Supportive care included proton pump inhibitor therapy and red blood cell transfusions as needed. The patient demonstrated good tolerance to rituximab therapy with early symptomatic improvement and stabilization of hematological parameters.</div></div><div><h3>Discussion</h3><div>This case illustrates several important aspects of MCL management in elderly patients. The presentation with gastrointestinal bleeding and extensive disease is typical for MCL, which frequently involves the GI tract at diagnosis. The moderate Ki-67 proliferation index (20%) suggested less aggressive biology, supporting a less intensive treatment approach.</div><div>The decision to use rituximab monotherapy reflects the growing recognition that treatment intensity must be individualized based on patient fitness and comorbidities. While intensive regimens like hyperCVAD or Nordic protocols achieve superior outc","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106165"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106147
Süleyman ARSLAN, İlhami Berber, İrfan Kuku, Emin Kaya, Mehmet Ali Erkurt, Ahmet Sarıcı, Mehmet Özcan
<div><h3>Introduction</h3><div>Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) resulting from severely reduced activity of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), a metalloproteinase responsible for cleaving von Willebrand factor (vWF). It is characterized by disseminated platelet-rich microvascular thrombi leading to organ ischemia, neurological abnormalities, renal dysfunction, thrombocytopenia, and microangiopathic hemolytic anemia (MAHA).</div><div>Hereditary TTP (hTTP; also referred to as congenital TTP [cTTP] or Upshaw–Schulman syndrome) arises from pathogenic variants in the <em>ADAMTS-13</em> gene and follows an autosomal recessive inheritance pattern. Although extremely rare, it can be life-threatening. Patients with hTTP require special attention during certain life stages such as the neonatal period and pregnancy . In contrast to immune-mediated TTP (iTTP), which typically presents with a dramatic and acute onset, hTTP may manifest with a more insidious clinical picture including lethargy, impaired concentration, abdominal pain, and headache . Severe renal failure, although uncommon in iTTP, may occur in hTTP patients due to lifelong ADAMTS-13 deficiency, which can cause progressive accumulation of thrombi within the renal vasculature</div><div>Hematologic examination may reveal pallor, purpura, and jaundice as signs of hemolysis, while laboratory findings typically show thrombocytopenia, unconjugated hyperbilirubinemia, elevated LDH levels, and decreased haptoglobin . Peripheral blood smear is often diagnostic, demonstrating schistocytes, nucleated red blood cells, and polychromatic red cells, consistent with intravascular hemolysis .</div><div>Here, we describe the case of an 18-year-old patient with congenital TTP who was initially misdiagnosed with myelodysplastic syndrome (MDS) at an early age and received intermittent transfusions due to cytopenias. The aim of this case report is to raise clinical awareness regarding this rare and potentially fatal subtype of TTP, which can be rapidly and effectively treated if recognized early. In addition, it underscores the importance of reassessing patients at each presentation, even when a pre-existing diagnosis is available, and highlights the critical diagnostic value of peripheral blood smear, as the presence of schistocytes is pathognomonic for this condition.</div></div><div><h3>Case report</h3><div>We present the case of an 18-year-old female patient, with no family history of hematologic disorders, who has been followed since childhood for anemia and thrombocytopenia. At the age of 18, she was diagnosed with congenital thrombotic thrombocytopenic purpura (TTP) and treatment was initiated. Her hematologic evaluation began in 2009, at the age of three, due to anemia and thrombocytopenia, during which she received platelet and red blood cell transfusions. Following a bone marrow examination, she was di
{"title":"A RARE DIAGNOSIS IN ADULTS: HEREDITARY THROMBOTIC THROMBOCYTOPENIC PURPURA","authors":"Süleyman ARSLAN, İlhami Berber, İrfan Kuku, Emin Kaya, Mehmet Ali Erkurt, Ahmet Sarıcı, Mehmet Özcan","doi":"10.1016/j.htct.2025.106147","DOIUrl":"10.1016/j.htct.2025.106147","url":null,"abstract":"<div><h3>Introduction</h3><div>Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) resulting from severely reduced activity of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), a metalloproteinase responsible for cleaving von Willebrand factor (vWF). It is characterized by disseminated platelet-rich microvascular thrombi leading to organ ischemia, neurological abnormalities, renal dysfunction, thrombocytopenia, and microangiopathic hemolytic anemia (MAHA).</div><div>Hereditary TTP (hTTP; also referred to as congenital TTP [cTTP] or Upshaw–Schulman syndrome) arises from pathogenic variants in the <em>ADAMTS-13</em> gene and follows an autosomal recessive inheritance pattern. Although extremely rare, it can be life-threatening. Patients with hTTP require special attention during certain life stages such as the neonatal period and pregnancy . In contrast to immune-mediated TTP (iTTP), which typically presents with a dramatic and acute onset, hTTP may manifest with a more insidious clinical picture including lethargy, impaired concentration, abdominal pain, and headache . Severe renal failure, although uncommon in iTTP, may occur in hTTP patients due to lifelong ADAMTS-13 deficiency, which can cause progressive accumulation of thrombi within the renal vasculature</div><div>Hematologic examination may reveal pallor, purpura, and jaundice as signs of hemolysis, while laboratory findings typically show thrombocytopenia, unconjugated hyperbilirubinemia, elevated LDH levels, and decreased haptoglobin . Peripheral blood smear is often diagnostic, demonstrating schistocytes, nucleated red blood cells, and polychromatic red cells, consistent with intravascular hemolysis .</div><div>Here, we describe the case of an 18-year-old patient with congenital TTP who was initially misdiagnosed with myelodysplastic syndrome (MDS) at an early age and received intermittent transfusions due to cytopenias. The aim of this case report is to raise clinical awareness regarding this rare and potentially fatal subtype of TTP, which can be rapidly and effectively treated if recognized early. In addition, it underscores the importance of reassessing patients at each presentation, even when a pre-existing diagnosis is available, and highlights the critical diagnostic value of peripheral blood smear, as the presence of schistocytes is pathognomonic for this condition.</div></div><div><h3>Case report</h3><div>We present the case of an 18-year-old female patient, with no family history of hematologic disorders, who has been followed since childhood for anemia and thrombocytopenia. At the age of 18, she was diagnosed with congenital thrombotic thrombocytopenic purpura (TTP) and treatment was initiated. Her hematologic evaluation began in 2009, at the age of three, due to anemia and thrombocytopenia, during which she received platelet and red blood cell transfusions. Following a bone marrow examination, she was di","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106147"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106160
Birol Güvenç
<div><h3>Introduction</h3><div>Therapy-related chronic lymphocytic leukemia/small lymphocytic lymphoma (t-CLL/SLL) is uncommon compared with therapy-related AML/MDS. We report a breast-cancer survivor who evolved from a CD5-negative low-grade B-cell lymphoproliferative disorder (LPD) to classical CLL/SLL with <strong>unmutated IGHV</strong>, underscoring why targeted BTK inhibition may supersede chemo-immunotherapy in this setting.</div></div><div><h3>Methods</h3><div>Single-patient case review of prospectively collected data. We extracted longitudinal clinical, imaging (PET-CT), bone-marrow histology, multiparameter flow cytometry, and cytogenetics (FISH, IGHV mutation testing). Treatment decisions were individualized by a multidisciplinary team.</div></div><div><h3>Results</h3><div>A 1959-born woman had invasive ductal breast carcinoma (2009) treated with adriamycin–cyclophosphamide, weekly paclitaxel, and radiotherapy, achieving long-term remission. In 2018 bone marrow was normal; in 2019 splenectomy for progressive splenomegaly revealed florid follicular hyperplasia. Between 2020–2022, bone-marrow biopsies showed a <strong>low-grade B-cell LPD</strong> (CD20⁺, <strong>CD5–/CD23–/CD10–</strong>), managed with <strong>rituximab–bendamustine (8 cycles)</strong>, yielding metabolic complete remission.</div><div>In 2025 she re-presented with profound fatigue and anemia. Labs showed marked lymphocytosis (WBC 46 × 10⁹/L), hemoglobin severely reduced, and PET-CT consistent with medullary disease. Bone marrow showed <strong>40–50%</strong> intertrabecular lymphoid infiltration. <strong>Flow cytometry now demonstrated classical CLL/SLL</strong> (CD19⁺, CD20⁺, <strong>CD5⁺, CD23⁺</strong>, κ-restriction). Molecular work-up: <strong>IGHV unmutated</strong>; FISH: <strong>monoallelic del(13q); del(17p)/del(11q) negative</strong>. Given prior anthracycline exposure/radiation and the high-risk biology conferred by unmutated IGHV despite isolated 13q deletion, the tumor board selected <strong>acalabrutinib plus rituximab</strong> rather than re-exposure to chemo-immunotherapy. Transfusion support and infection prophylaxis accompanied therapy planning.</div></div><div><h3>Discussion</h3><div>This case is notable for: (i) <strong>Therapy-related CLL/SLL</strong> emerging years after breast-cancer treatment—an under-recognized survivorship risk; (ii) <strong>Phenotypic evolution</strong> from an initially <strong>CD5-negative</strong> indolent B-cell LPD to <strong>typical CD5⁺/CD23⁺ CLL/SLL</strong>, highlighting clonal drift and the need for repeat immunophenotyping at relapse; (iii) <strong>Risk adjudication</strong> where <strong>unmutated IGHV</strong> outweighs the generally favorable isolated <strong>13q deletion</strong>, steering first-line choice away from bendamustine-rituximab toward <strong>BTK-inhibitor–based therapy</strong>; and (iv) pragmatic considerations in a previously anthracycline-exposed patient, favoring targeted agents for efficacy and
{"title":"From CD5-Negative Indolent B-Cell LPD to Therapy-Related CLL/SLL with Unmutated IGHV After Breast Cancer: Rationale for BTK-Inhibitor–Based First-Line Therapy","authors":"Birol Güvenç","doi":"10.1016/j.htct.2025.106160","DOIUrl":"10.1016/j.htct.2025.106160","url":null,"abstract":"<div><h3>Introduction</h3><div>Therapy-related chronic lymphocytic leukemia/small lymphocytic lymphoma (t-CLL/SLL) is uncommon compared with therapy-related AML/MDS. We report a breast-cancer survivor who evolved from a CD5-negative low-grade B-cell lymphoproliferative disorder (LPD) to classical CLL/SLL with <strong>unmutated IGHV</strong>, underscoring why targeted BTK inhibition may supersede chemo-immunotherapy in this setting.</div></div><div><h3>Methods</h3><div>Single-patient case review of prospectively collected data. We extracted longitudinal clinical, imaging (PET-CT), bone-marrow histology, multiparameter flow cytometry, and cytogenetics (FISH, IGHV mutation testing). Treatment decisions were individualized by a multidisciplinary team.</div></div><div><h3>Results</h3><div>A 1959-born woman had invasive ductal breast carcinoma (2009) treated with adriamycin–cyclophosphamide, weekly paclitaxel, and radiotherapy, achieving long-term remission. In 2018 bone marrow was normal; in 2019 splenectomy for progressive splenomegaly revealed florid follicular hyperplasia. Between 2020–2022, bone-marrow biopsies showed a <strong>low-grade B-cell LPD</strong> (CD20⁺, <strong>CD5–/CD23–/CD10–</strong>), managed with <strong>rituximab–bendamustine (8 cycles)</strong>, yielding metabolic complete remission.</div><div>In 2025 she re-presented with profound fatigue and anemia. Labs showed marked lymphocytosis (WBC 46 × 10⁹/L), hemoglobin severely reduced, and PET-CT consistent with medullary disease. Bone marrow showed <strong>40–50%</strong> intertrabecular lymphoid infiltration. <strong>Flow cytometry now demonstrated classical CLL/SLL</strong> (CD19⁺, CD20⁺, <strong>CD5⁺, CD23⁺</strong>, κ-restriction). Molecular work-up: <strong>IGHV unmutated</strong>; FISH: <strong>monoallelic del(13q); del(17p)/del(11q) negative</strong>. Given prior anthracycline exposure/radiation and the high-risk biology conferred by unmutated IGHV despite isolated 13q deletion, the tumor board selected <strong>acalabrutinib plus rituximab</strong> rather than re-exposure to chemo-immunotherapy. Transfusion support and infection prophylaxis accompanied therapy planning.</div></div><div><h3>Discussion</h3><div>This case is notable for: (i) <strong>Therapy-related CLL/SLL</strong> emerging years after breast-cancer treatment—an under-recognized survivorship risk; (ii) <strong>Phenotypic evolution</strong> from an initially <strong>CD5-negative</strong> indolent B-cell LPD to <strong>typical CD5⁺/CD23⁺ CLL/SLL</strong>, highlighting clonal drift and the need for repeat immunophenotyping at relapse; (iii) <strong>Risk adjudication</strong> where <strong>unmutated IGHV</strong> outweighs the generally favorable isolated <strong>13q deletion</strong>, steering first-line choice away from bendamustine-rituximab toward <strong>BTK-inhibitor–based therapy</strong>; and (iv) pragmatic considerations in a previously anthracycline-exposed patient, favoring targeted agents for efficacy and","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106160"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a rare extramedullary tumor composed of myeloblasts. It may occur de novo, concurrently with acute myeloid leukemia (AML), or as a relapse of previously treated AML. Oral cavity involvement is rare, and isolated presentations without bone marrow disease pose significant diagnostic challenges . MS is biologically considered equivalent to AML and should be treated accordingly, even in the absence of systemic disease .
Case Presentation
A 51-year-old woman presented with left facial swelling and dysphagia. MRI revealed a large mass in the left retromolar trigone extending to the skull base and infratemporal region with associated mandibular bone destruction. Incisional biopsy showed sheets of immature myeloid cells. Immunohistochemistry was positive for CD117, CD34, myeloperoxidase (MPO), and CD99, with a Ki-67 proliferation index of ∼40%, confirming myeloid sarcoma. PET-CT revealed a hypermetabolic mass (SUVmax 7.27) and ipsilateral cervical lymphadenopathy but no systemic FDG-avid disease. Bone marrow biopsy showed no leukemic infiltration The patient was treated for acute myeloid leukemia and was started on a 7+3 chemotherapy protocol. The patient is being monitored during the post-treatment cytopenic period.
Conclusion
ConclusionThis case highlights the diagnostic complexity of isolated myeloid sarcoma in an unusual location. Comprehensive immunophenotypic analysis is essential for diagnosis. Although marrow was uninvolved, the patient was initiated on AML-type induction chemotherapy due to the high risk of progression . Early systemic treatment, rather than localized therapy alone, is critical to avoid transformation into overt leukemia . Systemic chemotherapy using AML-like regimens should be commenced early, even in nonleukemic disease. Surgery and/or radiotherapy may be indicated for symptomatic lesions or tumors causing local organ dysfunction or obstruction. Allogeneic hematopoietic stem cell transplantation has demonstrated promising results, particularly in patients who achieved complete remission with AML-induction protocols, and recent advances in genetic profiling may enable the development of novel targeted therapies . Clinicians should maintain a high index of suspicion for MS in atypical head and neck masses.
{"title":"MYELOID SARCOMA PRESENTING IN THE RETROMOLAR TRIGONE WITHOUT MARROW INVOLVEMENT","authors":"Berrak Çağla ŞENOL ARSLAN, Ali TURUNÇ, Ayşegül Ezgi ÇETİN, Birol GÜVENÇ","doi":"10.1016/j.htct.2025.106152","DOIUrl":"10.1016/j.htct.2025.106152","url":null,"abstract":"<div><h3>Introduction</h3><div>Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a rare extramedullary tumor composed of myeloblasts. It may occur de novo, concurrently with acute myeloid leukemia (AML), or as a relapse of previously treated AML. Oral cavity involvement is rare, and isolated presentations without bone marrow disease pose significant diagnostic challenges . MS is biologically considered equivalent to AML and should be treated accordingly, even in the absence of systemic disease .</div></div><div><h3>Case Presentation</h3><div>A 51-year-old woman presented with left facial swelling and dysphagia. MRI revealed a large mass in the left retromolar trigone extending to the skull base and infratemporal region with associated mandibular bone destruction. Incisional biopsy showed sheets of immature myeloid cells. Immunohistochemistry was positive for CD117, CD34, myeloperoxidase (MPO), and CD99, with a Ki-67 proliferation index of ∼40%, confirming myeloid sarcoma. PET-CT revealed a hypermetabolic mass (SUVmax 7.27) and ipsilateral cervical lymphadenopathy but no systemic FDG-avid disease. Bone marrow biopsy showed no leukemic infiltration The patient was treated for acute myeloid leukemia and was started on a 7+3 chemotherapy protocol. The patient is being monitored during the post-treatment cytopenic period.</div></div><div><h3>Conclusion</h3><div>ConclusionThis case highlights the diagnostic complexity of isolated myeloid sarcoma in an unusual location. Comprehensive immunophenotypic analysis is essential for diagnosis. Although marrow was uninvolved, the patient was initiated on AML-type induction chemotherapy due to the high risk of progression . Early systemic treatment, rather than localized therapy alone, is critical to avoid transformation into overt leukemia . Systemic chemotherapy using AML-like regimens should be commenced early, even in nonleukemic disease. Surgery and/or radiotherapy may be indicated for symptomatic lesions or tumors causing local organ dysfunction or obstruction. Allogeneic hematopoietic stem cell transplantation has demonstrated promising results, particularly in patients who achieved complete remission with AML-induction protocols, and recent advances in genetic profiling may enable the development of novel targeted therapies . Clinicians should maintain a high index of suspicion for MS in atypical head and neck masses.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106152"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106114
Şengül BARAN Yerlikaya
<div><h3>Case Description</h3><div>A 73-year-old male was first diagnosed with PV (hemoglobin >18 g/dL, hematocrit >55%, JAK2 V617F positive) in 2016. He was managed with low-dose aspirin and phlebotomy; hydroxyurea was added later.</div><div>In 2019, routine CBC showed persistent lymphocytosis (lymphocytes ∼12 × 10^9/L). Flow cytometry demonstrated CD5+, CD19+, CD23+, FMC7– B-cells comprising 68% of lymphocytes, confirming Rai stage I CLL. No active treatment was initiated.</div><div>In 2020, during evaluation for COVID-like respiratory symptoms, thoracic CT revealed a during evaluation for a COVID-19-suspected cough and dyspnea, thoracic CT revealed a 20 × 14 mm left upper lobe mass with mediastinal lymphadenopathy with mediastinal lymphadenopathy. Bronchoscopic biopsy confirmed adenocarcinoma. EGFR exon 21 L858R mutation was present; ALK and ROS1 were negative. PET–CT staged disease at IIIB. Standard chemoradiotherapy was declined by the patient. Erlotinib treatment was initiated in March 2020. Concurrent progression of CLL with B symptoms prompted introduction of chlorambucil 10 mg daily for 7 days in a 28-day cycle.</div><div>At 3-month follow-up, CT scan showed near-complete regression of primary lung lesion and mediastinal nodes. CBC normalized. JAK2 V617F mutation, positive in 2016, was undetectable via allele-specific PCR (<1% allele burden). The patient exhibited ECOG 1 and continued erlotinib and chlorambucil with no grade ≥2 toxicity.</div></div><div><h3>Timeline</h3><div>• 2016: PV diagnosis (JAK2 V617F+) → aspirin/phlebotomy</div><div>• 2019: Rai stage IV CLL diagnosis+ chlorambucil</div><div>• 2020: NSCLC diagnosis (EGFR L858R+), start erlotinib</div><div>• 2021: Near-complete response, hematologic normalization, JAK2 negativity</div></div><div><h3>Diagnostic Assessment</h3><div>Routine labs and molecular assays performed at a reference laboratory confirmed JAK2 mutation status. Flow cytometry was consistent with CLL immunophenotype. NSCLC diagnosis followed standard bronchoscopic sampling; molecular analysis used validated PCR panels and sequencing.</div></div><div><h3>Therapeutic Intervention</h3><div>• <strong>Erlotinib</strong>: 150 mg PO daily as standard first-line for EGFR-mutant NSCLC[^3].</div><div>• <strong>Chlorambucil</strong>: 10 mg PO daily for 7/28 cycle for symptomatic Rai stage IV CLL, selected for low toxicity in elderly[^4].</div></div><div><h3>Follow-Up and Outcomes</h3><div>• <strong>At 3 Months:</strong> Dramatic radiologic regression; normalization of hematologic parameters; JAK2 mutation undetectable.</div><div>• Continued stable on erlotinib + chlorambucil with no significant toxicity; quality of life maintained.</div></div><div><h3>Discussion</h3><div>This case is unique in that:</div><div>• <strong>Sequential triple malignancy</strong>: PV, CLL, and EGFR-mutant NSCLC rarely occur together.</div><div>• <strong>Therapeutic synergy</strong>: Dual-targeted therapy produced durable responses in both
{"title":"CASE REPORT: A RARE TRIPLE MALIGNANCY – JAK2-POSITIVE POLYCYTHEMIA VERA, CHRONIC LYMPHOCYTIC LEUKEMIA AND EGFR-MUTANT STAGE IIIB NON–SMALL CELL LUNG ADENOCARCINOMA WITH UNUSUAL CLINICAL COURSE","authors":"Şengül BARAN Yerlikaya","doi":"10.1016/j.htct.2025.106114","DOIUrl":"10.1016/j.htct.2025.106114","url":null,"abstract":"<div><h3>Case Description</h3><div>A 73-year-old male was first diagnosed with PV (hemoglobin >18 g/dL, hematocrit >55%, JAK2 V617F positive) in 2016. He was managed with low-dose aspirin and phlebotomy; hydroxyurea was added later.</div><div>In 2019, routine CBC showed persistent lymphocytosis (lymphocytes ∼12 × 10^9/L). Flow cytometry demonstrated CD5+, CD19+, CD23+, FMC7– B-cells comprising 68% of lymphocytes, confirming Rai stage I CLL. No active treatment was initiated.</div><div>In 2020, during evaluation for COVID-like respiratory symptoms, thoracic CT revealed a during evaluation for a COVID-19-suspected cough and dyspnea, thoracic CT revealed a 20 × 14 mm left upper lobe mass with mediastinal lymphadenopathy with mediastinal lymphadenopathy. Bronchoscopic biopsy confirmed adenocarcinoma. EGFR exon 21 L858R mutation was present; ALK and ROS1 were negative. PET–CT staged disease at IIIB. Standard chemoradiotherapy was declined by the patient. Erlotinib treatment was initiated in March 2020. Concurrent progression of CLL with B symptoms prompted introduction of chlorambucil 10 mg daily for 7 days in a 28-day cycle.</div><div>At 3-month follow-up, CT scan showed near-complete regression of primary lung lesion and mediastinal nodes. CBC normalized. JAK2 V617F mutation, positive in 2016, was undetectable via allele-specific PCR (<1% allele burden). The patient exhibited ECOG 1 and continued erlotinib and chlorambucil with no grade ≥2 toxicity.</div></div><div><h3>Timeline</h3><div>• 2016: PV diagnosis (JAK2 V617F+) → aspirin/phlebotomy</div><div>• 2019: Rai stage IV CLL diagnosis+ chlorambucil</div><div>• 2020: NSCLC diagnosis (EGFR L858R+), start erlotinib</div><div>• 2021: Near-complete response, hematologic normalization, JAK2 negativity</div></div><div><h3>Diagnostic Assessment</h3><div>Routine labs and molecular assays performed at a reference laboratory confirmed JAK2 mutation status. Flow cytometry was consistent with CLL immunophenotype. NSCLC diagnosis followed standard bronchoscopic sampling; molecular analysis used validated PCR panels and sequencing.</div></div><div><h3>Therapeutic Intervention</h3><div>• <strong>Erlotinib</strong>: 150 mg PO daily as standard first-line for EGFR-mutant NSCLC[^3].</div><div>• <strong>Chlorambucil</strong>: 10 mg PO daily for 7/28 cycle for symptomatic Rai stage IV CLL, selected for low toxicity in elderly[^4].</div></div><div><h3>Follow-Up and Outcomes</h3><div>• <strong>At 3 Months:</strong> Dramatic radiologic regression; normalization of hematologic parameters; JAK2 mutation undetectable.</div><div>• Continued stable on erlotinib + chlorambucil with no significant toxicity; quality of life maintained.</div></div><div><h3>Discussion</h3><div>This case is unique in that:</div><div>• <strong>Sequential triple malignancy</strong>: PV, CLL, and EGFR-mutant NSCLC rarely occur together.</div><div>• <strong>Therapeutic synergy</strong>: Dual-targeted therapy produced durable responses in both","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106114"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106116
Berra Nur İşçi, Birol Güvenç, İdil Yürekli
Introduction
Kaposi sarcoma (KS) is a rare vascular tumor strongly associated with human herpesvirus 8 (HHV-8) and typically seen in immunocompromised states such as HIV/AIDS or post-transplant settings. However, with the increasing use of immunomodulatory therapies in hematologic malignancies, KS has also been reported in patients receiving Janus kinase (JAK) inhibitors. We present a case of HHV-8-positive cutaneous Kaposi sarcoma developing in a patient with primary myelofibrosis under ruxolitinib treatment.
Methods
A 72-year-old female with a 2-year history of intermediate-2 risk primary myelofibrosis, positive for the JAK2 V617F mutation, was being followed in our hematology department. She had been on ruxolitinib (2 × 10 mg/day) for symptom control, which provided initial improvement in systemic complaints and splenomegaly. However, after 14 months of treatment, she developed painless violaceous plaques and nodules on her lower extremities, raising suspicion for Kaposi sarcoma. Dermatologic examination confirmed the presence of multiple dark purple nodules predominantly on the left lower leg. A punch biopsy was performed, and histopathological examination revealed spindle-cell proliferation consistent with Kaposi sarcoma. Immunohistochemical staining was strongly positive for HHV-8.
Results
Laboratory evaluation revealed hemoglobin of 9.2 g/dL, white blood cell count of 13,000/mm³, and platelet count of 120,000/mm³. Peripheral smear showed typical findings of myelofibrosis, including teardrop-shaped erythrocytes. HIV, HBV, and HCV tests were all negative. Abdominal ultrasonography confirmed stable splenomegaly (19 cm). The ruxolitinib treatment was discontinued, and hydroxyurea was initiated as an alternative. Given that the Kaposi lesions were localized and the patient remained asymptomatic, systemic chemotherapy was not started. The patient is being followed with close dermatological and hematological monitoring.
Discussion
This case highlights a rare but clinically significant complication of ruxolitinib therapy in a patient with primary myelofibrosis. JAK inhibition may lead to immune dysregulation, impaired antiviral T-cell responses, and viral reactivation—particularly HHV-8 in susceptible individuals. Although KS is commonly associated with HIV, this patient had no underlying immunodeficiency other than the JAK inhibitor–mediated suppression. The temporal relationship between ruxolitinib exposure and KS onset, combined with HHV-8 positivity and regression of symptoms after discontinuation of the drug, supports a probable causal association. Clinicians should remain vigilant for unusual infections or neoplasms in patients undergoing JAK inhibitor therapy.
{"title":"HHV-8 Positive Kaposi Sarcoma in a Myelofibrosis Patient Treated with Ruxolitinib: A Rare but Clinically Relevant Association","authors":"Berra Nur İşçi, Birol Güvenç, İdil Yürekli","doi":"10.1016/j.htct.2025.106116","DOIUrl":"10.1016/j.htct.2025.106116","url":null,"abstract":"<div><h3>Introduction</h3><div>Kaposi sarcoma (KS) is a rare vascular tumor strongly associated with human herpesvirus 8 (HHV-8) and typically seen in immunocompromised states such as HIV/AIDS or post-transplant settings. However, with the increasing use of immunomodulatory therapies in hematologic malignancies, KS has also been reported in patients receiving Janus kinase (JAK) inhibitors. We present a case of HHV-8-positive cutaneous Kaposi sarcoma developing in a patient with primary myelofibrosis under ruxolitinib treatment.</div></div><div><h3>Methods</h3><div>A 72-year-old female with a 2-year history of intermediate-2 risk primary myelofibrosis, positive for the JAK2 V617F mutation, was being followed in our hematology department. She had been on ruxolitinib (2 × 10 mg/day) for symptom control, which provided initial improvement in systemic complaints and splenomegaly. However, after 14 months of treatment, she developed painless violaceous plaques and nodules on her lower extremities, raising suspicion for Kaposi sarcoma. Dermatologic examination confirmed the presence of multiple dark purple nodules predominantly on the left lower leg. A punch biopsy was performed, and histopathological examination revealed spindle-cell proliferation consistent with Kaposi sarcoma. Immunohistochemical staining was strongly positive for HHV-8.</div></div><div><h3>Results</h3><div>Laboratory evaluation revealed hemoglobin of 9.2 g/dL, white blood cell count of 13,000/mm³, and platelet count of 120,000/mm³. Peripheral smear showed typical findings of myelofibrosis, including teardrop-shaped erythrocytes. HIV, HBV, and HCV tests were all negative. Abdominal ultrasonography confirmed stable splenomegaly (19 cm). The ruxolitinib treatment was discontinued, and hydroxyurea was initiated as an alternative. Given that the Kaposi lesions were localized and the patient remained asymptomatic, systemic chemotherapy was not started. The patient is being followed with close dermatological and hematological monitoring.</div></div><div><h3>Discussion</h3><div>This case highlights a rare but clinically significant complication of ruxolitinib therapy in a patient with primary myelofibrosis. JAK inhibition may lead to immune dysregulation, impaired antiviral T-cell responses, and viral reactivation—particularly HHV-8 in susceptible individuals. Although KS is commonly associated with HIV, this patient had no underlying immunodeficiency other than the JAK inhibitor–mediated suppression. The temporal relationship between ruxolitinib exposure and KS onset, combined with HHV-8 positivity and regression of symptoms after discontinuation of the drug, supports a probable causal association. Clinicians should remain vigilant for unusual infections or neoplasms in patients undergoing JAK inhibitor therapy.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106116"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106115
Naciye Nur Tozluklu, Birol Güvenç
<div><h3>Introduction</h3><div>Chronic lymphocytic leukemia represents the most common adult leukemia in Western countries, with autoimmune hemolytic anemia occurring as a complication in 5-10% of cases. AIHA as the presenting feature of CLL is uncommon, particularly in young adults where CLL incidence is extremely rare. The immunophenotypic heterogeneity of CLL, including atypical variants, may influence both clinical presentation and treatment response.</div></div><div><h3>Case Reports</h3><div>Case 1: An 84-year-old female presented with progressive fatigue, weakness, and dyspnea. Laboratory evaluation revealed severe anemia (Hb: 9.3 g/dL), marked leukocytosis (42.36 × 10³/μL), and thrombocytopenia. Direct antiglobulin test was strongly positive (3+), confirming warm-type AIHA. Flow cytometry demonstrated classic CLL immunophenotype: CD19+ (93%), CD5+ (95%), CD23+ (84%), CD20+ (52%), with absent CD38 expression suggesting favorable-risk disease. Bone marrow biopsy confirmed CLL/SLL with 50% infiltration. Treatment with prednisolone rapidly resolved hemolysis, followed by ibrutinib therapy for CLL. The patient achieved sustained remission over 12 months with corticosteroid discontinuation after 3 months.</div><div>Case 2: A 25-year-old male presented with dyspnea, palpitations, and fatigue. Initial workup revealed severe anemia (Hb: 7.8 g/dL), reticulocytosis (6.8%), and elevated LDH with spherocytes on peripheral smear. Direct antiglobulin test was strongly positive (4+). Investigation revealed lymphocytosis (14,200/mm³, 68% lymphocytes) with atypical CLL immunophenotype: CD5+/CD19+/FMC7+/CD23-, distinguishing it from typical CLL while excluding mantle cell lymphoma through negative cyclin D1. TP53 abnormalities were absent. Initial prednisolone therapy provided insufficient response, prompting rituximab monotherapy (375 mg/m² × 4 cycles). The patient achieved complete hematologic response with hemoglobin normalization (11.6 g/dL), reticulocyte count resolution, and lymphocytosis improvement.</div></div><div><h3>Discussion</h3><div>These cases illustrate important clinical principles in CLL-associated AIHA management. The elderly patient presented with classic CLL immunophenotype and favorable prognostic markers (CD38-negative), supporting the choice of BTK inhibitor therapy appropriate for her age and comorbidities. The young adult case demonstrated atypical CLL immunophenotype (FMC7+/CD23-), representing a variant phenotype that required careful differentiation from mantle cell lymphoma.</div><div>The treatment approaches differed significantly based on age and disease characteristics. The elderly patient benefited from targeted therapy (ibrutinib) combined with corticosteroids, while the young patient achieved excellent response with rituximab monotherapy after steroid failure. This highlights the importance of individualized treatment selection based on patient factors and disease biology.</div><div>Both cases emphasize the critical role o
{"title":"Autoimmune Hemolytic Anemia as the Presenting Feature of Chronic Lymphocytic Leukemia: Two Contrasting Cases Across Different Age Groups","authors":"Naciye Nur Tozluklu, Birol Güvenç","doi":"10.1016/j.htct.2025.106115","DOIUrl":"10.1016/j.htct.2025.106115","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic lymphocytic leukemia represents the most common adult leukemia in Western countries, with autoimmune hemolytic anemia occurring as a complication in 5-10% of cases. AIHA as the presenting feature of CLL is uncommon, particularly in young adults where CLL incidence is extremely rare. The immunophenotypic heterogeneity of CLL, including atypical variants, may influence both clinical presentation and treatment response.</div></div><div><h3>Case Reports</h3><div>Case 1: An 84-year-old female presented with progressive fatigue, weakness, and dyspnea. Laboratory evaluation revealed severe anemia (Hb: 9.3 g/dL), marked leukocytosis (42.36 × 10³/μL), and thrombocytopenia. Direct antiglobulin test was strongly positive (3+), confirming warm-type AIHA. Flow cytometry demonstrated classic CLL immunophenotype: CD19+ (93%), CD5+ (95%), CD23+ (84%), CD20+ (52%), with absent CD38 expression suggesting favorable-risk disease. Bone marrow biopsy confirmed CLL/SLL with 50% infiltration. Treatment with prednisolone rapidly resolved hemolysis, followed by ibrutinib therapy for CLL. The patient achieved sustained remission over 12 months with corticosteroid discontinuation after 3 months.</div><div>Case 2: A 25-year-old male presented with dyspnea, palpitations, and fatigue. Initial workup revealed severe anemia (Hb: 7.8 g/dL), reticulocytosis (6.8%), and elevated LDH with spherocytes on peripheral smear. Direct antiglobulin test was strongly positive (4+). Investigation revealed lymphocytosis (14,200/mm³, 68% lymphocytes) with atypical CLL immunophenotype: CD5+/CD19+/FMC7+/CD23-, distinguishing it from typical CLL while excluding mantle cell lymphoma through negative cyclin D1. TP53 abnormalities were absent. Initial prednisolone therapy provided insufficient response, prompting rituximab monotherapy (375 mg/m² × 4 cycles). The patient achieved complete hematologic response with hemoglobin normalization (11.6 g/dL), reticulocyte count resolution, and lymphocytosis improvement.</div></div><div><h3>Discussion</h3><div>These cases illustrate important clinical principles in CLL-associated AIHA management. The elderly patient presented with classic CLL immunophenotype and favorable prognostic markers (CD38-negative), supporting the choice of BTK inhibitor therapy appropriate for her age and comorbidities. The young adult case demonstrated atypical CLL immunophenotype (FMC7+/CD23-), representing a variant phenotype that required careful differentiation from mantle cell lymphoma.</div><div>The treatment approaches differed significantly based on age and disease characteristics. The elderly patient benefited from targeted therapy (ibrutinib) combined with corticosteroids, while the young patient achieved excellent response with rituximab monotherapy after steroid failure. This highlights the importance of individualized treatment selection based on patient factors and disease biology.</div><div>Both cases emphasize the critical role o","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106115"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><h3>Introduction</h3><div>Histiocytic sarcoma (HS) is an exceptionally rare and aggressive hematopoietic malignancy, representing less than 1% of hematologic neoplasms [1]. No standardized therapeutic regimen exists; patients are often treated with lymphoma-like regimens such as CHOP or ICE, with limited efficacy and median survival of approximately six months [2,1]. Recent advances in molecular pathology have revealed recurrent BRAF^V600E mutations, ALK rearrangements, and PD-L1 expression, providing new diagnostic and therapeutic implications [3]. Case-based evidence suggests that PD-1 inhibitors may induce durable responses in select patients with PD-L1–positive HS [4,5].</div></div><div><h3>Case Presentation</h3><div>A 28-year-old male presented with abdominal pain and swelling. Imaging demonstrated a large intra-abdominal mass with peritoneal implants. Histopathology confirmed HS, positive for CD45, CD163, and CD14, with a Ki-67 index of 80%. Bone marrow biopsy was normocellular. Molecular analysis excluded BRAF and ALK alterations but demonstrated PD-L1 expression with a tumor proportion score (TPS) of 1–49% and a combined positive score (CPS) of 35%. The patient was started on ICE chemotherapy (ifosfamide, carboplatin, etoposide). Following biomarker analysis, nivolumab was introduced beginning with the second cycle. The treatment was well tolerated, and subsequent PET-CT demonstrated marked metabolic regression with clinical improvement. Follow-up abdominal imaging confirmed complete radiological response, with disappearance of the initially described mesenteric mass.</div></div><div><h3>Conclusion</h3><div>Discussion HS poses a therapeutic challenge because of its aggressive course and lack of standardized therapy [2,1]. Conventional chemotherapy regimens have limited durability, and reported responses are often transient. The presence of PD-L1 expression provided a rationale for incorporating a PD-1 inhibitor, even at moderate expression levels, consistent with emerging literature [4]. Previous case reports have demonstrated clinical benefit from pembrolizumab and nivolumab in PD-L1–positive HS, including durable complete responses [5]. In this patient, radiological assessment corroborated complete remission after combined ICE and nivolumab, supporting the potential role of checkpoint inhibition in improving depth of response. This case represents one of the few documented examples of combining intensive chemotherapy with checkpoint blockade in HS, highlighting the potential synergistic role of immunotherapy.Conclusion This case illustrates the rarity and therapeutic complexity of HS. The addition of nivolumab to ICE chemotherapy, guided by PD-L1 expression, resulted in meaningful clinical response in a young patient with advanced disease. These findings underscore the importance of integrated histopathological and molecular assessment in guiding personalized management for HS.Keywords: Histiocytic sarcoma; Nivolumab; ICE protocol;
{"title":"THERAPEUTIC CHALLENGE IN HISTIOCYTIC SARCOMA: A CASE REPORT OF NIVOLUMAB ADDITION TO THE ICE PROTOCOL","authors":"Ali Turunç, Berrak Çağla Şenol Arslan, Ayşegül Ezgi Çetin, Birol Güvenç","doi":"10.1016/j.htct.2025.106119","DOIUrl":"10.1016/j.htct.2025.106119","url":null,"abstract":"<div><h3>Introduction</h3><div>Histiocytic sarcoma (HS) is an exceptionally rare and aggressive hematopoietic malignancy, representing less than 1% of hematologic neoplasms [1]. No standardized therapeutic regimen exists; patients are often treated with lymphoma-like regimens such as CHOP or ICE, with limited efficacy and median survival of approximately six months [2,1]. Recent advances in molecular pathology have revealed recurrent BRAF^V600E mutations, ALK rearrangements, and PD-L1 expression, providing new diagnostic and therapeutic implications [3]. Case-based evidence suggests that PD-1 inhibitors may induce durable responses in select patients with PD-L1–positive HS [4,5].</div></div><div><h3>Case Presentation</h3><div>A 28-year-old male presented with abdominal pain and swelling. Imaging demonstrated a large intra-abdominal mass with peritoneal implants. Histopathology confirmed HS, positive for CD45, CD163, and CD14, with a Ki-67 index of 80%. Bone marrow biopsy was normocellular. Molecular analysis excluded BRAF and ALK alterations but demonstrated PD-L1 expression with a tumor proportion score (TPS) of 1–49% and a combined positive score (CPS) of 35%. The patient was started on ICE chemotherapy (ifosfamide, carboplatin, etoposide). Following biomarker analysis, nivolumab was introduced beginning with the second cycle. The treatment was well tolerated, and subsequent PET-CT demonstrated marked metabolic regression with clinical improvement. Follow-up abdominal imaging confirmed complete radiological response, with disappearance of the initially described mesenteric mass.</div></div><div><h3>Conclusion</h3><div>Discussion HS poses a therapeutic challenge because of its aggressive course and lack of standardized therapy [2,1]. Conventional chemotherapy regimens have limited durability, and reported responses are often transient. The presence of PD-L1 expression provided a rationale for incorporating a PD-1 inhibitor, even at moderate expression levels, consistent with emerging literature [4]. Previous case reports have demonstrated clinical benefit from pembrolizumab and nivolumab in PD-L1–positive HS, including durable complete responses [5]. In this patient, radiological assessment corroborated complete remission after combined ICE and nivolumab, supporting the potential role of checkpoint inhibition in improving depth of response. This case represents one of the few documented examples of combining intensive chemotherapy with checkpoint blockade in HS, highlighting the potential synergistic role of immunotherapy.Conclusion This case illustrates the rarity and therapeutic complexity of HS. The addition of nivolumab to ICE chemotherapy, guided by PD-L1 expression, resulted in meaningful clinical response in a young patient with advanced disease. These findings underscore the importance of integrated histopathological and molecular assessment in guiding personalized management for HS.Keywords: Histiocytic sarcoma; Nivolumab; ICE protocol;","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106119"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106125
Berrak Çağla Şenol, Ayşegül Ezgi Çetin, Ali Turunç, Birol Güvenç
<div><h3>Case Report</h3><div>A 59-year-old male (weight: 65 kg, height: 168 cm) presented in September 2024 with a progressively enlarging mass in the right maxillary region extending toward the temporal area with sphenoid bone proximity. The patient complained of maxillary distortion and pain but denied B symptoms including fever, night sweats, or weight loss.</div><div>Physical examination revealed facial asymmetry with palpable right maxillary swelling. Initial biopsy of the maxillary mass demonstrated CD20-positive extranodal marginal zone lymphoma consistent with MALT lymphoma histology.</div><div>Staging F-18 FDG PET/CT performed on October 4, 2024, revealed a hyperintense soft tissue mass in the right maxillary region with sphenoid bone invasion showing SUVmax 6.81. Additionally, a 16 × 10 mm lymph node in the right level 2 cervical chain demonstrated SUVmax 4.22. No pathological FDG uptake was detected in the thorax, abdomen, or skeletal system, confirming localized disease.</div><div>Based on the diagnosis of localized EMZL with bone invasion and cervical lymph node involvement, standard R-CHOP chemotherapy was initiated on September 24, 2024. The regimen consisted of rituximab 375 mg/m² (day 1), cyclophosphamide 750 mg/m² (day 1), doxorubicin 50 mg/m² (day 1), vincristine 1.4 mg/m² (day 1), and prednisolone 100 mg daily for 5 days. Supportive care included G-CSF (filgrastim) for neutropenia prophylaxis and antiemetics (ondansetron, granisetron).</div><div>During treatment, the patient developed E. coli pneumonia, which resolved with appropriate antibiotic therapy and supportive care. Despite this complication, the treatment protocol was successfully completed.</div><div>Interim PET-CT evaluation on December 25, 2024, demonstrated significant metabolic response with maxillary lesion SUVmax decreasing from 6.81 to 2.92, accompanied by dimensional reduction. Cervical lymph node involvement was no longer detectable, yielding a Deauville score of 2, consistent with partial metabolic remission.</div><div>Follow-up PET-CT after completion of 4 cycles in March 2025 revealed complete disappearance of pathological FDG uptake throughout the body. The maxillary region showed no residual mass formation, maintaining Deauville score 2, confirming complete metabolic remission.</div><div>The patient tolerated treatment well overall and entered surveillance follow-up without evidence of systemic dissemination or bone marrow involvement.</div></div><div><h3>Discussion</h3><div>This case represents a rare presentation of EMZL involving the maxillofacial region with sphenoid bone invasion. The excellent response to standard R-CHOP therapy challenges the traditional approach of radiotherapy alone for localized EMZL, particularly in cases with bone involvement where complete surgical resection may not be feasible. The use of PET-CT for treatment response assessment proved invaluable, providing objective metabolic parameters through Deauville scoring system.
{"title":"Primary Extranodal Marginal Zone Lymphoma of the Maxilla with Sphenoid Bone Invasion: Excellent Response to R-CHOP Therapy","authors":"Berrak Çağla Şenol, Ayşegül Ezgi Çetin, Ali Turunç, Birol Güvenç","doi":"10.1016/j.htct.2025.106125","DOIUrl":"10.1016/j.htct.2025.106125","url":null,"abstract":"<div><h3>Case Report</h3><div>A 59-year-old male (weight: 65 kg, height: 168 cm) presented in September 2024 with a progressively enlarging mass in the right maxillary region extending toward the temporal area with sphenoid bone proximity. The patient complained of maxillary distortion and pain but denied B symptoms including fever, night sweats, or weight loss.</div><div>Physical examination revealed facial asymmetry with palpable right maxillary swelling. Initial biopsy of the maxillary mass demonstrated CD20-positive extranodal marginal zone lymphoma consistent with MALT lymphoma histology.</div><div>Staging F-18 FDG PET/CT performed on October 4, 2024, revealed a hyperintense soft tissue mass in the right maxillary region with sphenoid bone invasion showing SUVmax 6.81. Additionally, a 16 × 10 mm lymph node in the right level 2 cervical chain demonstrated SUVmax 4.22. No pathological FDG uptake was detected in the thorax, abdomen, or skeletal system, confirming localized disease.</div><div>Based on the diagnosis of localized EMZL with bone invasion and cervical lymph node involvement, standard R-CHOP chemotherapy was initiated on September 24, 2024. The regimen consisted of rituximab 375 mg/m² (day 1), cyclophosphamide 750 mg/m² (day 1), doxorubicin 50 mg/m² (day 1), vincristine 1.4 mg/m² (day 1), and prednisolone 100 mg daily for 5 days. Supportive care included G-CSF (filgrastim) for neutropenia prophylaxis and antiemetics (ondansetron, granisetron).</div><div>During treatment, the patient developed E. coli pneumonia, which resolved with appropriate antibiotic therapy and supportive care. Despite this complication, the treatment protocol was successfully completed.</div><div>Interim PET-CT evaluation on December 25, 2024, demonstrated significant metabolic response with maxillary lesion SUVmax decreasing from 6.81 to 2.92, accompanied by dimensional reduction. Cervical lymph node involvement was no longer detectable, yielding a Deauville score of 2, consistent with partial metabolic remission.</div><div>Follow-up PET-CT after completion of 4 cycles in March 2025 revealed complete disappearance of pathological FDG uptake throughout the body. The maxillary region showed no residual mass formation, maintaining Deauville score 2, confirming complete metabolic remission.</div><div>The patient tolerated treatment well overall and entered surveillance follow-up without evidence of systemic dissemination or bone marrow involvement.</div></div><div><h3>Discussion</h3><div>This case represents a rare presentation of EMZL involving the maxillofacial region with sphenoid bone invasion. The excellent response to standard R-CHOP therapy challenges the traditional approach of radiotherapy alone for localized EMZL, particularly in cases with bone involvement where complete surgical resection may not be feasible. The use of PET-CT for treatment response assessment proved invaluable, providing objective metabolic parameters through Deauville scoring system. ","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106125"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106186
Tanju Atamer
<div><div>Thrombosis occurs when the delicate balance between prothrombotic and anticoagulant forces is impaired. It usually develops due to multiple factors. When multiple risk factors come together, the anticoagulant systems cannot resist procoagulant forces and thrombosis may develop as a result.</div><div>Thrombosis due to hypercoagulability is usually seen clinically as venous thromboembolism (VTE) and rarely as arterial thrombosis. VTE can be seen as deep vein thrombosis (DVT) or pulmonary embolism. DVT most often manifests itself in the legs and rarely in the abdominal or intra-pelvic veins.</div><div>The hereditary or acquired factors are involved in the etiology of venous thromboembolism. Clinically, VTE is observed in those who are due to hereditary factors, while venous or arterial thromboses may be observed in those who are due to acquired causes. Hypercoagulability due to acquired causes is observed more often (70%) and they have a greater risk of thrombosis.</div><div>Venous thromboembolism is reported to occur in 1/10,000 people per year under the age of 40 and 1/1000 people per year over the age of 75. Hereditary thrombophilia causes are rare in the population. Although different rates are reported according to the world geography, The R506Q mutation in coagulation factor V, also known as the Factor V Leiden (FVL) mutation is the most common among them (3-8%). It is rare in far east countries. FVL mutation is the most common cause among hereditary hypercoagulabilities (50%). Clinically, young age, idiopathic thrombosis, thrombosis in an unusual place (upper extremity, mesenteric vein, portal vein, renal vein, cerebral vein) are noteworthy. Recurrence of thrombosis and a family history of venous thromboembolism are common.</div><div>Since the findings are not specific in the diagnosis of venous thromboembolism, the patient's medical history, family history and examination findings should be evaluated together. Determination of thrombosis risk scores, D-Dimer test, blood chemistry, lung X-ray and ECG are included as the first examinations in the patient. In patients with a negative D-Dimer test, a further examination is usually not needed. The subject of which tests to perform and when to perform in VTE cases requires expertise. In cases of idiopathic thrombosis, occurring at a young age, or recurrent, genetic or coagulation tests may be planned. Since test results may be misleading during the acute thrombosis period, it is more appropriate to schedule the tests a few weeks later or after the end of treatment. In patients with a high thrombosis risk score and elevated D-dimer levels, extremity vein Doppler ultrasonography and computed pulmonary angiography are used as imaging studies.</div><div>Oral or parenteral anticoagulants are used in the treatment of venous thromboembolism. These include low molecular weight heparin, FXa inhibitors (apixaban, rivaroxaban), and vitamin K antagonist (warfarin). The most commonly used are low-mol
{"title":"HYPERCOAGULABILITY: ETIOLOGY, DIAGNOSIS AND TREATMENT PRINCIPLES","authors":"Tanju Atamer","doi":"10.1016/j.htct.2025.106186","DOIUrl":"10.1016/j.htct.2025.106186","url":null,"abstract":"<div><div>Thrombosis occurs when the delicate balance between prothrombotic and anticoagulant forces is impaired. It usually develops due to multiple factors. When multiple risk factors come together, the anticoagulant systems cannot resist procoagulant forces and thrombosis may develop as a result.</div><div>Thrombosis due to hypercoagulability is usually seen clinically as venous thromboembolism (VTE) and rarely as arterial thrombosis. VTE can be seen as deep vein thrombosis (DVT) or pulmonary embolism. DVT most often manifests itself in the legs and rarely in the abdominal or intra-pelvic veins.</div><div>The hereditary or acquired factors are involved in the etiology of venous thromboembolism. Clinically, VTE is observed in those who are due to hereditary factors, while venous or arterial thromboses may be observed in those who are due to acquired causes. Hypercoagulability due to acquired causes is observed more often (70%) and they have a greater risk of thrombosis.</div><div>Venous thromboembolism is reported to occur in 1/10,000 people per year under the age of 40 and 1/1000 people per year over the age of 75. Hereditary thrombophilia causes are rare in the population. Although different rates are reported according to the world geography, The R506Q mutation in coagulation factor V, also known as the Factor V Leiden (FVL) mutation is the most common among them (3-8%). It is rare in far east countries. FVL mutation is the most common cause among hereditary hypercoagulabilities (50%). Clinically, young age, idiopathic thrombosis, thrombosis in an unusual place (upper extremity, mesenteric vein, portal vein, renal vein, cerebral vein) are noteworthy. Recurrence of thrombosis and a family history of venous thromboembolism are common.</div><div>Since the findings are not specific in the diagnosis of venous thromboembolism, the patient's medical history, family history and examination findings should be evaluated together. Determination of thrombosis risk scores, D-Dimer test, blood chemistry, lung X-ray and ECG are included as the first examinations in the patient. In patients with a negative D-Dimer test, a further examination is usually not needed. The subject of which tests to perform and when to perform in VTE cases requires expertise. In cases of idiopathic thrombosis, occurring at a young age, or recurrent, genetic or coagulation tests may be planned. Since test results may be misleading during the acute thrombosis period, it is more appropriate to schedule the tests a few weeks later or after the end of treatment. In patients with a high thrombosis risk score and elevated D-dimer levels, extremity vein Doppler ultrasonography and computed pulmonary angiography are used as imaging studies.</div><div>Oral or parenteral anticoagulants are used in the treatment of venous thromboembolism. These include low molecular weight heparin, FXa inhibitors (apixaban, rivaroxaban), and vitamin K antagonist (warfarin). The most commonly used are low-mol","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106186"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：