Chronic Myeloid Leukemia, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome resulting from a reciprocal translocation between chromosomes 9 and 22 [t9;22] that gives rise to a BCR::ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase in developed countries. Tyrosine kinase inhibitor (TKI) therapy is a highly effective treatment option for patients with chronic phase-CML. The primary goal of TKI therapy in patients with chronic phase-CML is to prevent disease progression to accelerated phase-CML or blast phase-CML. Discontinuation of TKI therapy with careful monitoring is feasible in selected patients. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase-CML.

Multiple Genomic Alterations, Including a Novel AFF4::IRF1 Fusion Gene, in a Treatment-Refractory Blastic Plasmacytoid Dendritic-Cell Neoplasm: A Case Report and Literature Review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with an aggressive clinical course and poor prognosis. The genetic abnormalities in BPDCN are heterogeneous; therefore, its molecular pathogenesis and the prognostic importance of genomic alterations associated with the disease are not well defined. Here we report a case of BPDCN with a novel AFF4::IRF1 fusion predicted to lead to a loss-of-function of the IRF1 tumor suppressor, somatic mutations of ASXL1, TET2, and MYD88, as well as multiple intrachromosomal deletions. The patient showed resistance to Tagraxofusp and Venetoclax, and he died about 16 months after diagnosis. Considering the predicted effect of the AFF4::IRF1 fusion on IRF1's antitumor effects and immune regulation, and the possibility of its relevance to the aggressive course observed in this case, we propose further evaluation of the clinical significance of this fusion in BPDCN in future cooperative group studies and the consideration of therapeutic strategies aimed at restoring IRF1-dependent antineoplastic effects in such cases.

Angiosarcoma of the Face: A Case Study and Literature Review of Local and Metastatic Angiosarcoma.

Angiosarcomas are vascular malignancies with a tendency to spread extensively both locally and systemically. We report a case of cutaneous angiosarcoma of the face in a 53-year-old man that was originally misdiagnosed as an abscess. Initially small, the lesion enlarged over a four-to-six-month period and began to bleed. Two shave biopsies were performed that returned a diagnosis of angiosarcoma. The patient underwent radical resection and lymph node dissection, which revealed positive margins and ten of forty-six positive lymph nodes. The patient was treated with paclitaxel and concurrent radiation therapy (RT). Restaging scans showed a new sclerotic lesion of the T10 vertebra, three hepatic lesions, and an adrenal lesion, all concerning for metastasis. Biopsy of one of the hepatic lesions was consistent with metastatic angiosarcoma. In this review, we discuss the presentation of cutaneous angiosarcoma, the importance of early diagnosis, and the treatment options available for metastatic disease that has failed first-line chemotherapy.

Hepatocellular Carcinoma: First Manifestation as Solitary Humeral Bone Metastasis.

Hepatocellular carcinoma (HCC) most commonly presents with abdominal pain or mass, fever of unknown etiology, weight loss, and decompensation of known liver disease or at an asymptomatic stage through surveillance. Rarely, presenting symptoms can be exclusively related to extrahepatic metastases. Herein, we write a case of a patient with no known liver disease, presenting with a pathological fracture of the proximal humerus bone secondary to a massive solitary metastasis from HCC. This case represents an unusual appendicular skeletal metastasis in a patient with unknown primary HCC, successfully treated with sorafenib. The prognosis of HCC patients with extrahepatic metastasis is poor, and in the presence of bone metastases, the mean survival rate is severely reduced. However, the multikinase inhibitor sorafenib has been the standard of treatment. Recently, there has been developments of other therapeutic class of drugs (i.e., immune check inhibitors), which have shown promising benefits and better side effect profiles. Still, there is a need for further studies, owing to challenges in recognizing cellular and molecular markers.

Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells.

BACKGROUND/AIM: Anticancer peptide PNC-27 binds to HDM-2 protein on cancer cell membranes inducing the formation of cytotoxic transmembrane pores. Herein, we investigated HDM-2 membrane expression and the effect of PNC-27 treatment on human non-stem cell acute myelogenous leukemia cell lines: U937, acute monocytic leukemia; OCI-AML3, acute myelomonocytic leukemia and HL60, acute promyelocytic leukemia. MATERIALS AND METHODS: We measured cell surface membrane expression of HDM-2 using flow cytometry. Cell viability was assessed using MTT assay while direct cytotoxicity was measured by lactate dehydrogenase (LDH) release and induction of apoptotic markers annexin V and caspase-3. RESULTS: HDM-2 is expressed at high levels in membranes of U937, OCI-AML3 and HL-60 cells. PNC-27 can bind to membrane HDM-2 to induce cell necrosis and LDH release within 4 h. CONCLUSION: Targeting membrane HDM-2 can be a potential strategy to treat leukemia. PNC-27 targeting membrane HDM-2 demonstrated significant anti-leukemia activity in a variety of leukemic cell lines.

Case report of rhabdomyosarcomatous transformation of a primary gastrointestinal stromal tumor (GIST).

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common primary mesenchymal neoplasm of the gastrointestinal tract. Mutations of KIT and platelet-derived growth factor receptor alpha have been well characterized in GISTs. Patients with KIT mutations are generally sensitive to treatment with tyrosine kinase inhibitors. However, some patients with GIST, while initially sensitive to TKIs, gain resistance in later stages of treatment. Heterologous rhabdomyomsarcomatous dedifferentiation of advanced GISTs after long-term imatinib mesylate (IM) therapy has been reported. In these cases, the underlying molecular mechanism of tumor progression and transformation is unclear. CASE PRESENTATION: We report one such patient with rhabdomyosarcomatous dedifferentiation of a GIST without metastatic disease after brief 3-month therapy with IM. The tumor was composed of two distinct phenotypes, a CD117 negative region with rhabdomyosarcomatous differentiation directly adjacent to a CD117 positive classic GIST region. Molecular analysis identified the activating KIT exon 11 mutation in both regions, indicating a common origin for both phenotypes. Additionally, the dedifferentiated component contained two synonymous variants in platelet-derived growth factor receptor alpha and KIT. The increased number of synonymous variants in the rhabdomyosarcomatous region may reflect increased genetic instability of this tumor that may have resulted in the loss of CD117 expression in the dedifferentiated component. CONCLUSION: This study adds to the growing consensus that rhabdomyosarcomatous GIST progresses from a common GIST primary tumor. The role of IM in this progression is uncertain; however short duration of IM treatment in this study supports the hypothesis that rhabdomyosarcomatous GIST progression is not a consequence of IM therapy. Furthermore, we provide additional information supporting the observation that CD117 negative rhabdomyosarcomatous transformation maintains the activating KIT variant without KIT expression.

Neuroleukemiosis: Diagnosis and management.

An exceedingly rare manifestation of leukemia, termed neuroleukemiosis, involves peripheral nerve infiltration by leukemic cells. Patients with neuroleukemiosis typically present with a peripheral neuropathy and/or chloromatous masses. The diagnosis is supported by, and established with, electrophysiologic testing, imaging, histopathology, and immunophenotyping. We present the case of 21 year old male with multiply relapsed M4 type of acute myelogenous leukemia (AML) who presented with extremity pain and was subsequently found to have multiple cervical, thoracic, and lumbosacral nerve root masses. A diagnosis of neuroleukemiosis was established via CT-guided biopsy and immunophenotyping. The patient's neuroleukemiosis responded well to chemotherapy, donor lymphocyte infusions, and spinal irradiation. The literature is reviewed regarding this interesting and rare clinical condition.

Multidisciplinary strategies in bloodless medicine and surgery for patients undergoing pancreatectomy.

BACKGROUND: Bloodless pancreatic surgery (BPS) is rarely performed and/or reported. We aim to characterize perioperative and anesthetic strategies in BPS. MATERIALS AND METHODS: A literature search was performed on MEDLINE looking for case reports/case series using search terms ("Jehovah's Witness" [All Fields]) AND ("Pancreatic Surgery" [All Fields] OR "Pancreaticoduodenectomy" [All Fields] OR "Distal Pancreatectomy" [All Fields]). Data regarding categorical variables are reported as proportions and quantitative continuous variables as medians with ranges or means with standard deviation. Forty-one patients requiring BPS are reported in the literature with three additional cases from our institution (n = 44). The data analyzed included clinicopathologic factors, BPS strategies, patient complications, and in-hospital mortality. RESULTS: The most common procedure and diagnosis were pancreaticoduodenectomy (n = 34, 77.3%) and pancreatic ductal adenocarcinoma (n = 12, 27.3%), respectively. Transfusion reduction strategies in BPS fell into three categories: preoperative, intraoperative, and postoperative. Preoperative strategies included iron supplementation (n = 24, 54.5%) and erythropoietin administration (n = 14, 41.2%). Intraoperative strategies included acute normovolemic hemodilution (n = 30, 68%) and cell saver (n = 4, 9.1%). Postoperative strategies included erythropoietin (n = 16, 48.5%) and iron supplementation (n = 16, 48.5%). Complications occurred in 21 (60%) patients. There was no in-hospital mortality among the 44 patients in this cohort. CONCLUSIONS: A broad spectrum of bloodless medicine and surgery practices were used based on patient selection, multidisciplinary practice, and preference. With careful perioperative and anesthetic management, BPS can be performed with good outcomes.

Solitary Skeletal Muscle Metastasis as First Site of Recurrence of Cervical Cancer: A Case Report.

Cervical cancer is the fourth most common cancer in women worldwide, with a large majority of prevalence (85%) in developing countries. As of 2012, it accounts for 7.5% of all female cancer deaths. Despite its high prevalence, skeletal muscle metastasis from cervical cancer is extremely uncommon. In our extensive literature search, we were able to find only 8 cases where skeletal muscle metastasis was the only site of recurrence. We report a case of a 52-year-old African-American woman with a past medical history of cervical cancer (stage IIIB) who presented with pain and swelling in her left upper arm over the preceding 2 months. MRI of the left upper arm showed a solid well-circumscribed mass measuring 7.0 × 2.8 × 2.5 cm, deep to the biceps. Biopsy of the mass revealed a metastatic squamous cell carcinoma that was p16-positive. PET scan showed that the lesion was the sole site of metastasis. She received local radiation with concurrent chemotherapy. Follow-up MRI 6 months after the completion of therapy showed resolution of the mass. She has remained disease-free for the last 24 months as evidenced by a PET/CT scan in May 2016. In this case report, we discuss the role of imaging and pathology in the diagnosis of a solitary metastatic lesion. This case also emphasizes the importance of a close follow-up which aids in early intervention, increasing overall survival.

Small Cell Cancer of the Genitourinary Tract: A Case Report and Review of the Literature.

Small cell carcinoma of the urinary tract is an extremely rare disease with very few cases reported in the literature. Its clinical course is aggressive, and the prognosis is poor. Here, we present a case of metastatic extrapulmonary small cell carcinoma of the upper urinary tract in a 74-year-old African-American male. He initially presented with gross hematuria, 20-pound weight loss, and abdominal pain for 2 months. CT imaging showed a 14.0 × 7.0 × 16.0 cm retroperitoneal mass within the left renal fossa; biopsy revealed a carcinoma which was positive for synaptophysin and chromogranin. The patient also had detectable neuroendocrine cells in his urine cytology, confirming the diagnosis of small cell carcinoma. He was treated with carboplatin and etoposide as extrapolated from the treatment of its pulmonary counterpart. Due to the rarity of urinary tract small cell carcinoma, no randomized studies exist to guide therapy or management.

Complete Response after Treatment with Neoadjuvant Chemoradiation with Prolonged Chemotherapy for Locally Advanced, Unresectable Adenocarcinoma of the Pancreas.

Surgery is the only chance for cure in pancreatic ductal adenocarcinoma. In unresectable, locally advanced pancreatic cancer (LAPC), the National Comprehensive Cancer Network (NCCN) suggests chemotherapy and consideration for radiation in cases of unresectable LAPC. Here we present a rare case of unresectable LAPC with a complete histopathological response after chemoradiation followed by surgical resection. A 54-year-old female presented to our clinic in December 2013 with complaints of abdominal pain and 30-pound weight loss. An MRI demonstrated a mass in the pancreatic body measuring 6.2 × 3.2 cm; biopsy revealed proven ductal adenocarcinoma. Due to splenic vein/artery and contiguous celiac artery encasement, she was deemed surgically unresectable. She was started on FOLFIRINOX therapy (three cycles), intensity modulated radiation to a dose of 54 Gy in 30 fractions concurrent with capecitabine, followed by FOLFIRI, and finally XELIRI. After 8 cycles of ongoing XELIRI completed in March 2015, restaging showed a remarkable decrease in tumor size, along with PET-CT revealing no FDG-avid uptake. She was reevaluated by surgery and taken for definitive resection. Histopathological evaluation demonstrated a complete R0 resection and no residual tumor. Based on this patient and literature review, this strategy demonstrates potential efficacy of neoadjuvant chemoradiation with prolonged chemotherapy, followed by surgery, which may improve outcomes in patients deemed previously unresectable.

Recurrent Gastrointestinal Stromal Tumors in the Imatinib Mesylate Era: Treatment Strategies for an Incurable Disease.

INTRODUCTION: Recurrence of gastrointestinal stromal tumors (GISTs) after surgical resection and imatinib mesylate (IM) adjuvant therapy poses a significant treatment challenge. We present the case of a patient who underwent surgical resection after recurrence and review the current literature regarding treatment. CASE PRESENTATION: A 58-year-old man with a large intra-abdominal jejunal GIST was treated with complete surgical resection followed by IM. The patient experienced disease recurrence 3.5 years later and underwent IM dose escalation and reresection. CONCLUSION: Current strategies to treat recurrent GIST include dose escalation, modifying adjuvant tyrosine kinase inhibitor therapy, and surgery. High-level evidence will be required to better define the combinatory roles of tyrosine kinase inhibitor therapy, guided by molecular profiling, and surgery in the management of recurrent GIST.

Two "childhood" malignancies in an elderly individual: a case report and discussion.

Rhabdomyosarcoma (RMS) is the most common soft-tissue tumor in childhood, but is extremely rare in elderly. We present a rare case of cardiac RMS, which developed 1 year after the diagnosis and management of acute lymphoblastic leukemia in a 68-year-old female. The occurrence of such phenomena is intriguing, especially in an individual without prior history of malignancy at a younger age. Through the review of the existing literature, we attempt to approach the pathogenesis and clinical manifestations of this rare clinical entity.

Intracerebral progression of Hodgkin lymphoma in a man with HIV.

Intracerebral relapse of Hodgkin lymphoma is a rare occurrence, with a reported incidence of < 0.5%. To the best of our knowledge, only 4 cases have been reported in the literature. We report the case of a human immunodeficiency virus (HIV)-seropositive man with disseminated Hodgkin lymphoma who presented with left facial weakness and sensory abnormalities as the only symptoms of disease progression 3 months after chemotherapy-induced disease remission. Because of the relative rarity of the condition, there are no randomized controlled trials or evidence-based strategies for managing patients with HIV and intracerebral Hodgkin lymphoma. The diagnostic difficulty of this case emphasizes the necessity for a high index of suspicion for the diagnosis of HIV-associated intracerebral lymphoma in the appropriate clinical setting. In the post-genomic era, the development of sophisticated clinical and/or molecular biomarkers could contribute to earlier diagnosis and potentially improve disease prognosis.

Appendiceal carcinoma: a diagnostic and therapeutic challenge.

Appendiceal carcinoma is a very rare clinical entity, constituting 1% of all colorectal malignancies and 1% of all appendectomy specimens. Appendiceal malignancies often present atypically, thus creating diagnostic challenges. We present a patient with mucinous carcinoma of the appendix who presented with hematuria and abdominal pain. Similar case reports are extremely rare in the literature, while typical presentations of appendiceal carcinoma include abdominal pain, abdominal mass, early satiety, nausea, and iron-deficiency anemia. Initially, the diagnostic investigation in our patient was focused on urinary tract disorders, but ultimately resulted in finding a mucinous appendiceal carcinoma. The carcinoma had invaded the urinary bladder and was disseminated in the peritoneal cavity. Aggressive cytoreductive surgery is the most common therapeutic approach for disseminated tumors, often followed by intraperitoneal chemotherapy. However, treatment should be individualized based on patient-specific parameters, such as the presence of comorbidities, performance status, as well as the presence of metastatic disease. Our patient had optimal cytoreduction with subsequent systemic therapy with 5-fluorouracil, leucovorin, oxaliplatin, and bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor. She completed her treatment regimen without complications and is currently being restaged. An integrative approach is required in the diagnostic investigation and management of appendiceal malignancies.

Thallium-201 imaging in evaluation of Hodgkin's disease.

PURPOSE: The role of Ga 67 in the evaluation of Hodgkin's disease has been widely established. Tl 201 has been used to evaluate a wide variety of malignant lesions. This prospective study was performed to evaluate the role of Tl 201 imaging in Hodgkin's disease at the time of initial presentation and in the assessment of response to therapy, relapse, and remission. METHODS: Fifty-one consecutive patients (23 female, 28 male) with known Hodgkin's disease underwent 111 Tl 201 and Ga 67 studies. The age range was 16-56 years (mean age, 34.7 years). The histopathologies included nodular sclerosis (in 31 cases), mixed cellularity (in 12), lymphocytic predominant (in five), lymphocytic depletion (in one), and unknown (in two). All patients underwent whole-body imaging after intravenous injection of 3 mCi of Tl 201 chloride and 10 mCi of Ga 67 citrate. Comparison with Ga 67 imaging, anatomical imaging (computed tomography and/or magnetic resonance imaging), and clinical correlation were performed. RESULTS: The combined analysis of all various histologies demonstrated that a comparison of Tl 201 with Ga 67 scintigraphy revealed a sensitivity of 0.76 versus 0.89; a specificity of 0.96 versus 0.73, an accuracy of 0.86 versus 0.81, a positive predictive value of 0.95 versus 0.77, and a negative predictive value of 0.81 versus 0.87. Tl 201 imaging was similar in sensitivity, specificity, and accuracy among the nodular sclerosis and the mixed-cellularity Hodgkin's disease. CONCLUSION: Tl 201 imaging offers more specificity with a higher positive predictive value in the diagnosis of Hodgkin's disease. The Ga 67 study is more sensitive than Tl 201 in the detection of disease. There is no significant difference in accuracy and negative predictive value between the two studies. Therefore, we recommend Tl 201 imaging in the initial evaluation and assessment of patients' response to radiation therapy and/or chemotherapy.

Occurrence of multiple myeloma in both donor and recipient after bone marrow transplantation.

The transplantation of malignant cells during allogeneic transplant is a rare occurrence. 27 months after donating progenitor cells, a diagnosis of multiple myeloma was made in a 6/6 HLA-phenotypically matched unrelated donor. The 42-year-old recipient transplanted for chronic phase chronic myeloid leukemia developed IgA myeloma 40 months after transplantation. Serum electrophoresis and bone marrow investigations established the diagnosis of IgA K multiple myeloma in both. This case illustrates the natural history and biology of multiple myeloma.