A comparative medical illustration detailing therapeutic pathways for Chronic Myeloid Leukemia (CML) within the bone marrow niche. The diagram contrasts conventional Tyrosine Kinase Inhibitor (TKI) therapy with Anti-BCR/ABL gene therapy. The top pathway illustrates 'Leukemic Hematopoiesis': following TKI therapy, a mixed population of yellow Hematopoietic Stem Cells (HSCs), light blue TKI-sensitive Leukemic Stem Cells (LSCs), and dark blue TKI-resistant LSCs is shown. Treatment cessation or resistance leads to relapse, characterized by the proliferation of myeloid/lymphoid CML cells. The lower pathway depicts the potential of gene therapy: 'Anti-BCR/ABL gene therapy' targets LSCs to silence the oncogene (BCR/ABL OFF). This results in 'Corrected LSCs' (depicted with yellow and blue stripes), which repopulate the niche alongside normal HSCs. The final outcome is 'Normal Hematopoiesis' and the eradication of CML, visualised by the presence of mature myeloid/lymphoid blood cells (orange). The diagram serves as an educational tool for hematology and oncology, emphasizing the limitations of protein-level inhibition versus genome-level editing in stem cell niches.

This diagnostic image displays a fluorescence in situ hybridization (FISH) analysis of human bone marrow cells, used primarily for detecting the BCR-ABL1 gene fusion associated with Chronic Myeloid Leukemia (CML). The image shows two blue-stained nuclei (DAPI) against a dark background. On the left, a larger metaphase cell exhibits a normal signal pattern with two distinct cyan/green signals and two distinct red signals (2G2R), representing the normal location of the ABL1 and BCR genes on their respective chromosomes. On the right, a smaller interphase cell demonstrates a fusion signal where a red and a cyan/green signal overlap or are closely apposed, indicative of a chromosomal translocation. This visual is a key educational tool for demonstrating molecular cytogenetics, specifically the dual-color, dual-fusion probe technique used in hematopathology to identify the Philadelphia chromosome.

Light microscopy of a bone marrow biopsy from hairy cell leukemia (HCL) shows diffuse infiltration by small to medium lymphoid cells with abundant clear cytoplasm and oval, occasionally reniform nuclei; the cytoplasm creates a fried egg appearance. Hairy projections may be highlighted by immunostaining and by DBA.44 positivity, along with CD11c, CD25, and CD103 markers. The marrow is commonly hypercellular in established disease, whereas early involvement may be hypocellular and mimic aplastic anemia. Prominent reticulin fibrosis is typical and can hinder aspirate yield, making core biopsy essential for assessing infiltration and baseline disease burden. Normal hematopoietic elements, especially the myeloid lineage, are reduced and may display dysplastic changes resembling myelodysplastic syndrome. Plasma cells and mast cells may be mildly increased. In some cases, hairy cells assume a spindle-shaped morphology. The neoplastic cells are typically monotonous with minimal prominent nucleoli, and cytoplasm may exhibit cytoplasmic processes. Unlike several small B-cell lymphomas, discrete cellular aggregates are uncommon, with diffuse replacement predominating. Immunohistochemistry and flow cytometry confirm the diagnosis via characteristic immunophenotype. Clinically, marrow involvement informs staging, prognosis, and treatment planning, though peripheral blood smear and immunophenotypic profiling often suffice for diagnosis. This image, captured at high magnification on a hematoxylin and eosin stained section, showcases classic hairy cell features.

Histopathology: Bone marrow biopsy prepared for light microscopy shows diffuse infiltration by hairy cells rather than well-formed nodules. The marrow is often hypercellular in established disease but can be hypocellular in early stages, mimicking aplastic anemia. Hairy cells appear monotonous with oval nuclei and abundant clear cytoplasm that yields a characteristic fried egg morphology on H&E sections. In some cases, hair-like cytoplasmic projections (hairy indentations) are accentuated with specialized staining such as DBA.44 immunostain, supporting a hairy cell leukemia (HCL) diagnosis. The tumor cells may display spindled forms; the immunophenotype typically includes DBA.44 positivity, and cells may express CD11c, CD25, and CD103 on broader panels. Normal hematopoietic elements, particularly myeloid precursors, are reduced and can show dysplastic changes reminiscent of myelodysplastic syndrome. Plasma cells and mast cells may be mildly increased. Significant reticulin fibrosis is common, contributing to difficult marrow aspirates and making core biopsy essential to determine the extent of marrow replacement. Although marrow evaluation is informative, many cases of HCL can be diagnosed from peripheral blood smear and immunophenotyping alone; however, the biopsy provides baseline disease burden and a reference for assessing therapeutic response and fibrosis progression. This image exemplifies classic HCL marrow involvement with fried egg cells and conspicuous reticulin fibrosis.

This composite educational image illustrates the clinical and laboratory findings of splenic infarction in a patient with Chronic Myeloid Leukemia (CML). Panel A is a grayscale abdominal ultrasound showing an enlarged spleen (splenomegaly) with multiple peripheral, wedge-shaped hypoechoic lesions consistent with splenic infarcts; calipers measure several zones between 1.58 cm and 3.21 cm. Panel B displays a non-enhanced axial CT scan of the upper abdomen, confirming the presence of multiple peripheral hypodense areas within the spleen, which correlate with the ultrasound findings of infarction. Panel C is a line graph correlating laboratory values over a 42-day period, showing the relationship between Phosphorus (mg/dL), Creatinine (mg/dL), and White Blood Cell (WBC) count. Notably, the graph demonstrates an extreme shift from hyperphosphatemia to severe hypophosphatemia (<0.5 mg/dL) as the WBC count rapidly increases, suggesting a high metabolic demand or 'tumor lysis-like' sequestration during a leukemic blast crisis. This visual set is used to teach the radiological presentation of vascular complications in hematologic malignancies and the interpretation of metabolic trends in aggressive leukemia.

Clinical photograph of a gross pathological specimen showing an enlarged, splenomegalic spleen post-emergency splenectomy. The organ displays a dark, reddish-purple discoloration and irregular surface texture consistent with hematologic pathology. A prominent 3 cm parenchymal laceration at the lower pole is indicated by a blue arrow, representing a traumatic or spontaneous grade three splenic injury. A red arrow identifies a ruptured subcapsular hematoma, appearing as an extensive, raised, lighter red mass covering more than 50% of the organ's surface. This specimen illustrates complications of splenomegaly, often secondary to conditions like Chronic Myeloid Leukemia (CML), where increased organ friability raises the risk of spontaneous rupture, hemorrhage, and subsequent hemoperitoneum.

This composite figure presents research data on Chronic Myeloid Leukemia (CML) development in wild-type (Wt) and Sipa1 knockout (Sipa1-/-) mice following Bcr-Abl+ hematopoietic progenitor cell (HPC) injection. Panel (a) displays Kaplan-Meier survival curves showing that Sipa1-/- mice are completely resistant to CML in unirradiated conditions (100% survival), while gamma-irradiation abolishes this resistance. Panel (b) provides quantitative and visual evidence of disease progression: Wt mice exhibit massive splenomegaly (spleen weights 0.4-0.8g) and high peripheral blood GFP+ leukemic cell proportions (~80-90%), whereas Sipa1-/- mice maintain normal spleen weights (~0.1g) and negligible circulating leukemic cells. Clinical photographs show the striking morphological difference between the enlarged, dark-red spleens of Wt mice and the normal-sized spleens of Sipa1-/- mice. Panel (c) shows survival curves based on varying intervals after irradiation, indicating that the host resistance in Sipa1-/- mice is radiosensitive and requires several months to recover. This content illustrates the role of the host microenvironment and Sipa1 in leukemia progression and immune-mediated rejection.

This gross pathology image depicts a human liver from an autopsy with chronic lymphocytic leukemia (CLL). The hepatic parenchyma bears numerous small whitish‑gray nodules scattered throughout the entire cut surface, corresponding to leukemic infiltrates concentrated in periportal areas. Macroscopically the nodules are subtle but conspicuous against the usually uniform red-brown background of healthy liver tissue. The periportal pattern reflects infiltration along portal tracts and within the surrounding lobular parenchyma, a recognized histopathologic correlate of CLL involvement. The liver is part of a disseminated leukemic process, as indicated by concurrent involvement of bone marrow, lymph nodes, spleen, and kidneys in this case, consistent with advanced systemic disease. The autopsy specimen provides direct visualization of organomegaly and parenchymal replacement by malignant lymphocytes, which may contribute to hepatic dysfunction in late-stage disease. Clinically, such hepatic infiltration can manifest as hepatomegaly, cholestasis, or cytopenias secondary to marrow failure. For education and research, this image illustrates an end-stage pattern of CLL hepatic involvement, helps differentiate lymphoid infiltration from focal hepatic metastases, and supports teaching about organ-wide dissemination. Note: image is a gross specimen photograph with a blue backdrop, illustrating macroscopic periportal nodularity and leukemic spread.

This is a peripheral blood smear prepared with Wright-Giemsa stain and examined under brightfield illumination at high magnification (approximately 1000x total, 100x objective with oil immersion). The smear displays predominantly erythrocytes with uniform pink cytoplasm and characteristic biconcave morphology, arranged singly with occasional rouleaux. Interspersed among the red cells are leukocytes with visible nuclei. Notably, two large lymphocyte-like cells or mononuclear leukocytes appear conspicuously larger than surrounding erythrocytes; these cells have round to oval, deeply basophilic nuclei with dense chromatin and scant, lightly basophilic cytoplasm. No visible granulocytic cytoplasm granules or multiple lobes are clearly resolved in this field, and there are no obvious nucleoli or cytoplasmic inclusions evident in these cells. The background lacks abnormal pigment or reticulocytosis. Overall cell morphology is consistent with a normal or mildly reactive hematologic smear; in a clinical context, additional data such as complete blood count, differential, and patient history would be needed to determine whether there is leukocytosis or blasts. This image serves as an educational reference for recognizing basic peripheral blood components, evaluating leukocyte size variation, and assessing RBC morphology for hematology training and diagnostic differential diagnoses. Additional cases and image contexts can reinforce recognition of hematologic normal variants and patterns.

Imaging modality: Bright-field microscopy of Wright-Giemsa stained peripheral blood smear. Anatomical target: circulating peripheral blood cells, with a focus on B-cell prolymphocytes. Visual features: a monomorphic population of medium-to-large lymphoid cells exhibiting round to slightly irregular nuclei, coarse chromatin, and prominent nucleoli; cytoplasm is basophilic and variably abundant; occasional cytoplasmic projections may be seen; the smear background shows scattered erythrocytes and platelets. Overall, leukocytosis with prolymphocytic predominance suggests a malignant B-cell process. Pathological context: morphological hallmarks of B-cell prolymphocytic leukemia (B-PLL), defined by prolymphocytes comprising more than 55% of circulating lymphoid cells in peripheral blood; cells may be part of a systemic leukemia involving bone marrow and spleen. Immunophenotype typically expresses B-cell markers (CD19, CD20) with light chain restriction; immunohistochemistry and flow cytometry are used for confirmation; distinction from mantle cell lymphoma (cyclin D1/MCL) and CLL with increased prolymphocytes is critical. Diagnostic significance: detection of prolymphocytic leukocytes guides prognosis and therapeutic planning, as B-PLL has an aggressive course and limited responsiveness to standard CLL regimens. Clinical correlation: patients are commonly elderly with fatigue, cytopenias, and organomegaly; accurate classification influences treatment choice and clinical trial eligibility; this image serves as an educational reference for hematology, pathology, and medical education.

Imaging modality: light microscopy of a hematoxylin and eosin stained bone-tissue section from the femur, obtained in a 65-year-old male with a pathologic fracture. The specimen demonstrates a diffuse, high-cellularity infiltrate composed predominantly of immature myeloid cells, including myeloblasts, promyelocytes, and eosinophilic myelocytes. The tumor occupies the medullary cavity and expands the bony trabeculae with scant extracellular stroma. Morphology shows round to oval cells with high nuclear-to-cytoplasmic ratio, fine chromatin, conspicuous nucleoli, and mitotic activity; occasional cells show eosinophilic cytoplasm consistent with eosinophilic myelocytes. The background marrow is overtaken by neoplastic hematopoietic elements, with little evidence of maturation toward segmented granulocytes. The tissue architecture is diffuse rather than organized into blasts arranged in clusters. The presence of eosinophilic myelocytes supports a myeloid lineage; the pattern is compatible with myeloid sarcoma (granulocytic sarcoma) with predominant blast-rich differentiation. Clinically, this finding indicates an extramedullary myeloid tumor and may be associated with acute myeloid leukemia or myelodysplastic syndromes. Accurate classification (blastic vs immature vs differentiated) informs prognosis and guides systemic therapy, including AML-type chemotherapy, targeted approaches, and bone-targeted strategies. Differential considerations include lymphoma, small round blue cell tumors, and Ewing sarcoma; correlation with peripheral blood and marrow studies is essential for staging and management.

This diagnostic image displays a fluorescence in situ hybridization (FISH) analysis of human bone marrow cells, used primarily for detecting the BCR-ABL1 gene fusion associated with Chronic Myeloid Leukemia (CML). The image shows two blue-stained nuclei (DAPI) against a dark background. On the left, a larger metaphase cell exhibits a normal signal pattern with two distinct cyan/green signals and two distinct red signals (2G2R), representing the normal location of the ABL1 and BCR genes on their respective chromosomes. On the right, a smaller interphase cell demonstrates a fusion signal where a red and a cyan/green signal overlap or are closely apposed, indicative of a chromosomal translocation. This visual is a key educational tool for demonstrating molecular cytogenetics, specifically the dual-color, dual-fusion probe technique used in hematopathology to identify the Philadelphia chromosome.

This diagnostic image demonstrates a human bone marrow cell during interphase, analyzed using Fluorescence In Situ Hybridization (FISH) technique. The cell nucleus is stained with a blue DAPI counterstain, providing a background for visualizing chromosomal probes. Within the nucleus, four distinct fluorescent signals are visible: two green (G) signals and two red (R) signals, establishing a '2G2R' pattern. This specific arrangement of discrete, non-fused spots indicates a normal signal pattern, specifically used in hematopathology to rule out chromosomal translocations such as the BCR-ABL1 fusion (Philadelphia chromosome) commonly associated with Chronic Myeloid Leukemia (CML). The absence of overlapping or fused 'yellow' signals confirms the lack of a fusion event in this specific cell. This image serves as an educational reference for normal cytogenetic results in clinical hematology and oncology.

A low-magnification light micrograph of a human bone marrow aspirate, likely stained with a Romanowsky-type stain (e.g., Giemsa or Wright-Giemsa). The image shows hypercellular marrow fragments characterized by dense, purple-stained hematopoietic cellular clusters interspersed with clear, round vacuoles representing adipose tissue (marrow fat). Within these hypercellular areas, there is evidence of megakaryocytic hyperplasia (marked megakaryocytosis). Prominent, large basophilic cells representing megakaryocytes are visible, some of which are indicated by dark blue arrows. The surrounding stroma appears mottled with varying cellular density. This diagnostic image demonstrates the hematological manifestations often associated with POEMS syndrome, specifically the proliferation of the megakaryocytic lineage within the marrow compartment.