Chronic Leukemia Pathology Study Guide

Chronic Leukemia

Chronic leukemia involves leukemia of mature blood cells.

Chronic leukemia is typically insidious in onset and visible in elderly adults.

Examples of chronic leukemias include:

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
Hairy cell leukemia (HCL)
Adult T-cell leukemia/lymphoma
Mycosis fungoides (MF)

Chronic Myeloid Leukemia. Peripheral blood (MGG stain): marked leukocytosis with granulocyte left shift Paulo Henrique Orlandi Mourao - Not altered. CC BY-SA 3.0
Chronic Myeloid Leukemia. Chronic myeloid leukemia in a 4 years old female. Peripheral blood (MGG stain). - Not altered. CC BY-SA 4.0
Chronic Lymphocytic Leukemia. Smudge cells in peripheral blood Dr Graham Beards - Not altered. CC BY-SA 3.
Chronic Lymphocytic Leukemia. Micrograph of a lymph node affected by B-CLL showing a characteristic proliferation center (right of image), composed of larger, lighter-staining, cells, H&E stain Nephron - Not altered. CC BY-SA 3.0
Chronic Lymphocytic Leukemia. High-power magnification (1000 X) of a Wright's stained peripheral blood smear showing chronic lymphocytic leukemia (CLL). The lymphocytes with the darkly staining nuclei and scant cytoplasm are the CLL cells. Vashi Donsk. Not Altered. CC BY-SA 3.0
Mycosis Fungoides. Skin lesions on the knee of a 52 year old male patient with Mycosis fungoides (also known as Alibert-Bazin syndrome), the most common form of cutaneous T-cell lymphoma. Bobjgalindo. Not altered. CC BY-SA 4.0
Fluorescence in situ hybridization (FISH) for the FIP1L1-PDGFRA rearrangement, and reverse transcription - polymerase chain reaction (RT-PCR) and sequencing analysis. (A) Schematic representation of the 4q12 region and FISH probe. (B) Loss of the orange signal indicates deletion of the 4q12 region (white arrow) in first case. (C) FISH results for second case. (D) RT-PCR was performed using RNA extracted from the patient's (first case) white blood cells (lane 1). EOL-1 cells were used as a positive control (lane 2). Size marker (M). (E) Sequencing analysis of the RT-PCR products revealed the fusion of FIP1L1, exon 12 and truncated PDGFRA, exon 12 (breakpoint is between the 84th and 85th nucleotides of exon 12). FIP1L1, Ensemble Gene ID ENSG00000145216; PDGFRA, Ensemble Gene ID, ENSG00000134853. Chronic eosinophilic leukemia with a FIP1L1-PDGFRA rearrangement: Two case reports and a review of Korean cases. Shin SY, Jung CW, Choi DC, Lee BJ, Kim HJ, Kim SH - Blood research (2015). Not altered. CC.
Peripheral blood (PB) smear and bone marrow (BM) aspirate findings of first case (A, B) and second case (C, D). (A) Eosinophilia (13.0×109/L) was observed in the PB (Wright-Giemsa, ×1,000). (B) Dysplastic eosinophils (sparse and mixed granules) were increased in the BM aspirate (Wright-Giemsa, ×1,000). (C) Eosinophilia (55.316×109/L) was observed in the PB (Wright-Giemsa, ×1,000). (D) The BM section was packed with eosinophils (hematoxylin-eosin, ×400). Chronic eosinophilic leukemia with a FIP1L1-PDGFRA rearrangement: Two case reports and a review of Korean cases. Shin SY, Jung CW, Choi DC, Lee BJ, Kim HJ, Kim SH - Blood research (2015). Not altered. CC.
Chronic Myelogenous Leukemia. A G-banded karyotype showing 46,XX,t(9;22)(q34;q11.2). Red arrows indicate involved chromosomes 9 and 22. b Fluorescence in situ hybridization using the Vysis Extra Signal probe showing the BCR–ABL fusion signal. Red arrow indicates a red–green fusion (yellow) signal which confirms a BCR (green)/ABL (red) translocation. Acute compartment syndrome as the initial manifestation of chronic-phase chronic myeloid leukemia: a case report and review of the literature. Nagase Y, Ueda S, Matsunaga H, Yoshioka A, Okada Y, Machida T, Nakata K, Mima F, Takeda R, Hayashi D, Iio S, Okita K, Narahara H, Yasunaga Y, Inui Y, Kawata S - Journal of medical case reports (2016). Not altered. CC.
Chronic Myelogenous Leukemia. Bone marrow aspirate (May-Giemsa staining) showing marked myeloid proliferation without any differentiation block. Acute compartment syndrome as the initial manifestation of chronic-phase chronic myeloid leukemia: a case report and review of the literature. Nagase Y, Ueda S, Matsunaga H, Yoshioka A, Okada Y, Machida T, Nakata K, Mima F, Takeda R, Hayashi D, Iio S, Okita K, Narahara H, Yasunaga Y, Inui Y, Kawata S - Journal of medical case reports (2016). Not altered. CC.
Chronic eosinophilic leukemia. Altered original to remove description. CC.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Photomicrography of the lymph node showing typical histology and immunophenotype of a chronic lymphoid leukemia diagnosis. A - Lymph node obliterated by small and mature lymphoid cells (H&E, 100X); B - CD20 membranous positivity (IH-Cell Marque™ L26 clone, 200X); C - CD23 positivity (IH-Cell Marque™ 1B12, 200X); D - CD5 aberrant positivity (IH-Cell Marque™ 4C7 clone, 200X); E - Ki67 low index positivity (IH-Cell Marque™ SP6 clone, 200X). Advanced chronic lymphoid leukemia with severe bronchopneumonia: an Autopsy Case Report. Amaral FG, Lima LG, Hatanaka VM, Siqueira SA, Duarte-Neto AN - Autopsy & case reports (2016). Not altered. CC.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Morphological appearances of chronic lymphocytic leukaemia (CLL) and CLL with >10% circulating prolymphocytes (CLL/PL). (A) Typical CLL. The majority of cells are small with clumped chromatin. (B) Typical CLL/PL. There is a mixture of prolymphocytes and typical CLL lymphocytes. (C) Typical CLL/PL showing small lymphocytes, prolymphocytes and an immunoblast. (D) Typical B‐cell prolymphocytic leukaemia (B‐PLL). The majority of cells have condensed non‐clumped chromatin and a single vesicular nucleolus. This panel is shown here for comparative purposes only, to illustrate the similar morphology of the prolymphocytes in B‐PLL to those seen in panels B and C. The majority of cells in B‐PLL are prolymphocytes and no small lymphocytes are seen. The usual “CLL score” is 0–1. B‐PLL is a distinct disorder and does not arise from a pre‐existing CLL. Magnification: panels A, B and C ×100; panel D ×60. The morphology of CLL revisited: the clinical significance of prolymphocytes and correlations with prognostic/molecular markers in the LRF CLL4 trial. British Journal of Haematology. Not altered. CC.

Chronic Lymphocytic Leukemia (CLL)

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is characterized by B cells that co-express CD5 and CD20.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most prevalent type of chronic leukemia.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) classically shows smudge cells and lymphocytes on blood smear.

Small lymphocytic lymphoma is characterized by lymph node involvement, which results in widespread lymphadenopathy.

Complications of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) include:

Autoimmune hemolytic anemia
Hypogammaglobulinemia
Risk of infections
Transformation to diffuse large B-cell lymphoma (Richter transformation)

The leading cause of death in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is hypogammaglobulinemia compounded by infection.

Chronic Lymphocytic Leukemia. Smudge cells in peripheral blood Dr Graham Beards - Not altered. CC BY-SA 3.
Chronic Lymphocytic Leukemia. Micrograph of a lymph node affected by B-CLL showing a characteristic proliferation center (right of image), composed of larger, lighter-staining, cells, H&E stain Nephron - Not altered. CC BY-SA 3.0
Chronic Lymphocytic Leukemia. High-power magnification (1000 X) of a Wright's stained peripheral blood smear showing chronic lymphocytic leukemia (CLL). The lymphocytes with the darkly staining nuclei and scant cytoplasm are the CLL cells. Vashi Donsk. Not Altered. CC BY-SA 3.0
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Photomicrography of the lymph node showing typical histology and immunophenotype of a chronic lymphoid leukemia diagnosis. A - Lymph node obliterated by small and mature lymphoid cells (H&E, 100X); B - CD20 membranous positivity (IH-Cell Marque™ L26 clone, 200X); C - CD23 positivity (IH-Cell Marque™ 1B12, 200X); D - CD5 aberrant positivity (IH-Cell Marque™ 4C7 clone, 200X); E - Ki67 low index positivity (IH-Cell Marque™ SP6 clone, 200X). Advanced chronic lymphoid leukemia with severe bronchopneumonia: an Autopsy Case Report. Amaral FG, Lima LG, Hatanaka VM, Siqueira SA, Duarte-Neto AN - Autopsy & case reports (2016). Not altered. CC.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Morphological appearances of chronic lymphocytic leukaemia (CLL) and CLL with >10% circulating prolymphocytes (CLL/PL). (A) Typical CLL. The majority of cells are small with clumped chromatin. (B) Typical CLL/PL. There is a mixture of prolymphocytes and typical CLL lymphocytes. (C) Typical CLL/PL showing small lymphocytes, prolymphocytes and an immunoblast. (D) Typical B‐cell prolymphocytic leukaemia (B‐PLL). The majority of cells have condensed non‐clumped chromatin and a single vesicular nucleolus. This panel is shown here for comparative purposes only, to illustrate the similar morphology of the prolymphocytes in B‐PLL to those seen in panels B and C. The majority of cells in B‐PLL are prolymphocytes and no small lymphocytes are seen. The usual “CLL score” is 0–1. B‐PLL is a distinct disorder and does not arise from a pre‐existing CLL. Magnification: panels A, B and C ×100; panel D ×60. The morphology of CLL revisited: the clinical significance of prolymphocytes and correlations with prognostic/molecular markers in the LRF CLL4 trial. British Journal of Haematology. Not altered. CC.

Hairy Cell Leukemia (HCL)

Hairy cell leukemia (HCL) is characterized by cytoplasmic processes that radiate from the malignant cells.

Hairy cell leukemia (HCL) is positive for tartrate-resistant acid phosphatase (TRAP) stain.

Symptoms of hairy cell leukemia (HCL) includes:

Splenomegaly (caused by an increase of hairy cells in the red pulp)
Fibrotic “dry tap” bone marrow aspiration

Lymphadenopathy is normally absent in hairy cell leukemia (HCL).

Hairy cell leukemia (HCL) is treated by adenosine deaminase inhibitor 2-chlorodeoxyadenosin (2-CdA).

The adenosine deaminase inhibitor 2-chlorodeoxyadenosin (2-CdA) causes the neoplastic B cells to accumulate adenosine to lethal amounts.

2-chlorodeoxyadenosin (2-CdA) is also known as Cladribine (aka Leustatin).

If treated hairy cell leukemia (HCL) has an excellent prognosis.

Hairy Cell Leukemia. Atypical hairy cell lymphocytes (arrows) seen in peripheral blood. Hairy cell leukemia - immunotargets and therapies. Basheer F, Bloxham DM, Scott MA, Follows GA - ImmunoTargets and therapy (2014). Not altered. CC.
Hairy Cell Leukemia. Hairy cell leukemia: Abnormal B cells look "hairy" under a microscope because of radial projections from their surface. Paulo Henrique Orlandi Mourao - Not altered. CC BY-SA 3.0
Hairy Cell Leukemia. Hairy cell leukemia Not altered. Public Domain
Hairy Cell Leukemia. Diagnostic pathologic findings for lymphomatous presentation of hairy cell leukemia. All stains at 400× except BRAFV600E (F) at 600×. A. Hematoxylin & Eosin stain showing small to medium sized cells with interspersed histiocytes. Further positive stains including CD20 (B), cyclin D1 (C), annexin A1 (D), CD200 (E), and BRAFV600E (F). Hairy Cell Lymphoma: A Potentially Under-Recognized Entity. Rare Tumors. Not altered. CC.
Hairy Cell Leukemia. Peripheral blood smear with occasional small lymphocytes showing ample pale cytoplasm and cytoplasmic projections “hairy cells.” Primary hairy cell leukemia/lymphoma of the breast: a case report and review of the literature. Pilichowska M, Shariftabrizi A, Mukand-Cerro I, Miller K - Case reports in pathology (2014). Not altered. CC.

Adult T-Cell Leukemia/Lymphoma (ATLL)

Adult T-cell leukemia/lymphoma is due to neoplastic proliferation of mature T cells.

Adult T-cell leukemia/lymphoma is linked to HTLV-1.

Adult T-cell leukemia/lymphoma is most prevalent in Japan and the Caribbean.

Symptoms of Adult T-cell leukemia/lymphoma include:

Rashes
Generalized lymphadenopathy
Hepatomegaly
Splenomegaly
Lytic (punched-out) bone lesions
Hypercalcemia

T-lymphoblastic leukemia. Peripheral blood smear containing leukemic cells (Wright's stain, ×200) (A). Bone marrow aspirate smear showing leukemic cells that are small-to-medium sized, with a high nuclear-to-cytoplasmic ratio (Wright-Giemsa stain, ×200 (B) and ×1,000 (C)). Biopsy section showing hypercellularity with heavy infiltration of immature cells (H&E, ×100) (D). Simultaneous translocation of both TCR Loci (14q11) with rare partner loci (Xq22 and 12p13) in a case of T-lymphoblastic leukemia. Kang DH, Kim SH, Jun JW, Lee YW, Shin HB, Ahn JY, Hong DS, Lee YK, Jeon BR - Annals of laboratory medicine (2012). Not altered. CC.
T-cell Acute Lymphoblastic Leukemia. Blasts in the bone marrow smear. T-cell Acute Lymphoblastic Leukemia with del (7) (q11.2q22) and Aberrant Expression of Myeloid Markers. Ahmadzadeh A, Saedi S, Jaseb K, Asnafi AA, Alghasi A, Saki N - International journal of hematology-oncology and stem cell research (2013).
T-Cell Prolymphocytic Leukemia_Flow Cytometry_Peripheral Blood Smear. Photomicrograph of peripheral blood smear showing prolymphocytes and eosinophils (H and E stain, 400×). Inset - Showing closer view of prolymphocytes. T-cell prolymphocytic leukemia with cutaneous involvement as the presenting feature. Ashturkar AV, Pathak GS, More YE, Bhandare A - Indian journal of dermatology (2012). Not altered. CC.
T-Cell Prolymphocytic Leukemia_Histology. Peripheral blood smear showing medium sized lymphoid cells, with oval nucleus, a visible nucleolus and moderate amount of basophilic agranular cytoplasm (Jenner-Giemsa, 1000×). Inset Lymphoid cells showing, dot-like staining with acid phosphatase, 1000×). T cell-prolymphocytic leukemia detected in a patient of breast cancer at the time of recurrence: a case report. Singhal M, Raina V, Gupta R, Das P - Cases journal (2010). Not altered. CC.
T-Cell Prolymphocytic Leukemia_CD3 IHC. Lymphoid cells showing strong positivity for CD3 on immunohistochemistry (H and E stain, 100×). T-cell prolymphocytic leukemia with cutaneous involvement as the presenting feature. Ashturkar AV, Pathak GS, More YE, Bhandare A - Indian journal of dermatology (2012). Not altered. CC.
T-Cell Prolymphocytic Leukemia_Clinical Image_Cutaneous Involvement_Pathosomes. Patient showing erythematous papules, macules, and plaques on the lower extremity. T-cell prolymphocytic leukemia with cutaneous involvement as the presenting feature. Ashturkar AV, Pathak GS, More YE, Bhandare A - Indian journal of dermatology (2012). Not altered. CC.
T-Cell Prolymphocytic Leukemia_Flow Cytometry. A: Scatter-plot showing predominant population of T-cells with bright CD8 expression (arrow) B (density-plot): uniform CD52 expression. C: Scatter-plot showing predominant population of T-cells with dim CD4 expression (arrow) D: And heterogeneous CD52 expression. "T-cell prolymphocytic leukemia (T-PLL), a heterogeneous disease exemplified by two cases and the important role of cytogenetics: a multidisciplinary approach". Tirado CA, Starshak P, Delgado P, Rao N - Experimental hematology & oncology (2012). Not altered. CC.
T-Cell Prolymphocytic Leukemia_Histology. A: Peripheral blood smear with lymphocytes, note cytoplasmic blebs. B: Bone marrow aspirate with numerous lymphocytes, note prominent nucleoli. "T-cell prolymphocytic leukemia (T-PLL), a heterogeneous disease exemplified by two cases and the important role of cytogenetics: a multidisciplinary approach". Tirado CA, Starshak P, Delgado P, Rao N - Experimental hematology & oncology (2012). Not altered. CC.

Mycosis Fungoides (MF)

Mycosis fungoides (MF) is due to the neoplastic proliferation of mature CD4+ T cells that infiltrate the skin.

Symptoms of mycosis fungoides (MF) includes:

Skin rashes (nodules and plaques)
Fatigue
Hepatomegaly

Histology of mycosis fungoides (MF) is characterized by malignant infiltration of neoplastic-T-cells in the epidermis that are known as Pautrier microabscesses.

Mycosis Fungoides. Histopathology of Pautrier microabscesses in cutaneous T cell lymphoma. Nooshin Bagherani, Bruce R. Smoller - Not altered. CC BY 4.0
Mycosis Fungoides. Plaque of mycosis fungoides on foot treated with imiquimod at Penn Medicine in Philadelphia, and then radiation at Lehigh Valley Hospital–Cedar Crest in Allentown Not altered. Public Domain
Mycosis Fungoides. Plaque of mycosis fungoides kilbad. Not altered. CC BY 3.0
Mycosis Fungoides. (A) Edematous dusky red to erythematous patches on the back and the left leg before treatment. (B) Remission on the back and left leg with addition of isotretinoin to methotrexate and psoralen plus ultraviolet A therapy. Woo YR, Lee HM, Lee JS, Koo DW - Annals of dermatology (2013). Not altered. CC.
Mycosis-Fungoides Pathology Histology (A) Epidermotrophism with clustered atypical lymphocytes in the epidermis and dense lymphocytic infiltrate with hyperchromatic nuclei in the dermis (H&E, ×40; inset: H&E, ×200). (B) The result of T-cell receptor-gamma gene rearrangement showed the monoclonality in polymerase chain reaction-heteroduplex analysis. Marker (lane M), specimen (lane S), negative control (lane N), positive control (lane P). Woo YR, Lee HM, Lee JS, Koo DW - Annals of dermatology (2013)

Sézary Syndrome

Sézary syndrome is a type of mycosis fungoides (MF) in which the malignant cells also circulate in the blood stream.

On a blood smear, Sézary syndrome characteristically shows lymphocytes with cerebriform nuclei (Sézary cells).