Background
Leukemias are neoplastic proliferations of the hematopoietic cells arising within the bone marrow. As a group, they are classified as acute and chronic. Acute leukemias have primitive cells called blasts and usually have a rapid and fatal course if untreated. They are further subdivided into acute lymphoblastic leukemias (ALL) and acute myeloblastic or acute non-lymphoblastic leukemias (AML or ANLL). Chronic leukemias are proliferations of relatively mature cells and have an indolent course. Chronic leukemias may transform and convert to acute leukemias with a clone of blast cells. They, too, are subdivided into chronic lymphocytic leukemias (CLL) and chronic myeloid or myelogenous leukemias (CML). Pathologists often perform sophisticated analysis of leukemia cells through a combination of flow cytometry and immunohistochemistry. The newer classification systems are largely the result of discoveries made by pathologists.
Leukemia-Acute Lymphoblastic (ALL)
Leukemia-Acute Myelogenous (AML)
Leukemia-Chronic Lymphocytic (CLL)
Leukemia-Chronic Myelogenous (CML)
Leukemia-Hairy Cell
Leukemia-Prolymphocytic
Myelodysplasia
Myeloproliferative Disorders (Essential Thrombocytosis, Polcythemia Vera, CML)
OUTLINE
HISTOLOGICAL TYPES CHARACTERIZATION VARIANTS GRANULOCYTIC SARCOMA (LEUKEMIA CUTIS) Consider this diagnosis if the cells have a CD43+ only phenotype with CD3- and CD20-
Most sensitive marker is myeloperoxidase
Neutrophil elastase is less sensitive
Chloracetate esterase (Leder stain) is specific but not sensitive-also stains mast cellsMyeloid leukemia cutis: a histologic and immunohistochemical review
Cibull TL, Thomas AB, O’Malley DP, Billings SD.
J Cutan Pathol 2008; 35: 180–185. Abstract quoteBackground: The histologic diagnosis of myeloid leukemia cutis (LC) can be difficult, requiring confirmatory immunohistochemical stains.
Objective: We reviewed 21 biopsy-proven cases of LC with emphasis on the use of immunohistochemistry in the diagnosis.
Materials and Methods: Clinical and histologic features were reviewed on 21 cases of biopsy proven LC. Immunohistochemical stains for CD4, CD34, CD56, CD68, CD117, CD123, TdT, lysozyme and myeloperoxidase were performed on 12 with available tissue blocks.
Results: Ages ranged from 24 to 88 years (mean = 57), with 12 men: 9 women. Primary hematologic diagnoses included acute myeloid leukemia (n = 14), myelodysplastic syndrome (n = 3), essential thrombocythemia (n = 1) and myeloid leukemia, NOS (n = 3). Monocytic myeloid LC was most common (35%). There was 100% positivity with CD68 and lysozyme. Myeloperoxidase, CD117 and CD34 immunostains were less sensitive in myeloid LC (58%, 33% and 17%, respectively). CD4 was positive in 67%. CD56 was positive in 33%.
Conclusion: Myeloid leukemia with monocytic differentiation more commonly involves the skin than other types of myeloid leukemia. CD68 and lysozyme immunostains, although not lineage specific for monocytes/macrophages, are the most sensitive immunostains in the detection of myeloid LC. Myeloperoxidase immunostains are useful, but immunostains for CD117 and CD34 are insufficiently sensitive. CD4 expression is common, but CD56 expression is not.
Leukemia cutis.Department of Pathology, The Methodist Hospital, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Am J Clin Pathol. 2008 Jan;129(1):130-42. Abstract quote
Leukemia cutis (LC) is a nonspecific term used for cutaneous manifestations of any type of leukemia. LC has a wide range of cutaneous manifestations, which can make it difficult to clinically distinguish LC from other skin lesions. Patients with LC usually have concomitant systemic leukemia, but occasionally skin involvement precedes the involvement of the bone marrow or peripheral blood. Thus, a skin biopsy can be the first indication of the presence of leukemia in a subset of patients.
The immunophenotyping of routinely processed skin biopsy specimens is very useful in establishing the diagnosis of LC. Although the molecular mechanisms explaining the pathogenesis of LC are not well defined, chemokine receptors and adhesion molecules may have an important role in skin tropism.
We review the literature and recent advances pertaining to LC, with special emphasis on the immunohistochemical assessment and possible mechanisms involved in skin tropism by leukemic cells. Myeloid Sarcoma Involving the Gynecologic TractA Report of 11 Cases and Review of the Literature
Mar Garcia Garcia, MD, etal. Am J Clin Pathol 2006;125:783-790Abstract quote
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Myeloid sarcoma can involve any anatomic site, but involvement of the gynecologic tract is uncommon.
We describe 11 women, 17 to 60 years old, with myeloid sarcoma involving the gynecologic tract, including 5 patients in whom myeloid sarcoma presented as an isolated mass. The uterus was the most frequently involved anatomic site, in 8 patients (5 corpus, 3 cervix). Each neoplasm diffusely infiltrated normal structures, and, cytologically 7 tumors were immature, 3 were differentiated, and 1 was blastic. In 9 cases assessed, immunohistochemical stains showed that all neoplasms were positive for myeloperoxidase and lysozyme; CD117 was positive in 7 of 8 cases, and cytochemical staining for naphthol AS-D chloroacetate was positive in all 6 neoplasms analyzed.
Following chemotherapy, complete remission and long-term survival were achieved in a subset of patients, as was particularly true for 2 patients (cases 8 and 10), with complete remission 12.5 and 31 years after diagnosis, respectively. Myeloid Sarcoma Involving the Testis
Jose R. Valbuena, MD, Joan H. Admirand, MD, Pei Lin, MD, and L. Jeffrey Medeiros, MD Am J Clin Pathol 2005;124:445-452 Abstract quote
Myeloid sarcoma is a neoplasm of immature granulocytes, monocytes, or both involving any extramedullary site. Myeloid sarcoma involving the testis, however, is uncommon and very rarely occurs as an isolated mass.
We describe 4 patients with myeloid sarcoma involving the testis, including 2 patients in whom the neoplasm was isolated to the testis (1 unilateral and 1 bilateral). Histologically, 4 neoplasms were poorly differentiated and 1 was blastic. Each neoplasm was shown to be of myeloid lineage, and negative for T- and B-cell specific antigens using immunohistochemical methods. One case was also positive for chloroacetate esterase.
In the literature, most cases of myeloid sarcoma involving the testis represent relapse or the initial presentation of acute myeloid leukemia. Including the 2 cases we report here, only 7 cases of myeloid sarcoma isolated to the testis have been reported.
- Myeloid sarcoma of appendix mimicking acute appendicitis.
Palomino-Portilla EA, Valbuena JR, Quinones-Avila Mdel P, Medeiros LJ.
Department of Pathology, Edgardo Rebagliati Hospital, Lima, Peru.
Arch Pathol Lab Med. 2005 Aug;129(8):1027-31. Abstract quote
CONTEXT: Myeloid sarcoma is a neoplasm of immature myeloid cells involving an extramedullary anatomic site that is usually, although not always, associated with acute myeloid leukemia. Any extramedullary site can be involved by myeloid sarcoma, but involvement of the cecal appendix is uncommon, and symptoms mimicking acute appendicitis as a result of appendiceal involvement are rare.
OBJECTIVE: To describe the clinicopathologic features of 2 patients with myeloid sarcoma involving the appendix who presented with right lower quadrant pain suggestive of acute appendicitis and prompting appendectomy.
DESIGN: Clinical information for both patients was obtained from the medical record. Routine hematoxylin-eosin-stained slides, naphthol-ASD-chloroacetate stain, and immunohistochemical stains for myeloid, B-cell, and T-cell antigens were prepared.
RESULTS: Peripheral blood and bone marrow were infiltrated by coexistent acute myeloid leukemia in case 1 but were negative for leukemia in case 2. In case 2, the patient had a history of acute myeloid leukemia that had been treated by an allogenic bone marrow transplant 7 months earlier. Histologic examination of the appendix revealed poorly differentiated myeloid sarcoma in both cases. Each neoplasm was positive for chloroacetate esterase, myeloperoxidase, lysozyme, and CD43 and was negative for CD3 and CD20.
CONCLUSIONS: Myeloid sarcoma involving the appendix can rarely cause pain or other symptoms mimicking acute appendicitis. A high index of suspicion combined with the use of cytochemical and immunohistochemical studies are helpful in establishing the diagnosis.Crystalline Inclusions in Granulocytic Sarcoma Report of 2 Cases and Ultrastructural Studies
James A. Strauchen, MD and Ronald E. Gordon, PhD
From the Department of Pathology, Mount Sinai School of Medicine, New York, NY. \
Arch Pathol Lab Med 2002;Vol. 126, No. 1, pp. 85–86. Abstract quote
Two cases of granulocytic sarcoma were found to contain numerous crystalline inclusions identified on hematoxylin-eosin–stained sections as clusters of pointed needlelike crystals present in foci of necrosis or within macrophages. The crystals were negative for chloroacetate esterase and myeloperoxidase. Electron microscopy demonstrated homogeneously dense, bipyramidal structures, indistinguishable from Charcot-Leyden crystals.
Granulocytic sarcomas may contain crystalline inclusions similar to Charcot-Leyden crystals; these structures should be distinguished from crystalline immunoglobulin inclusions occurring in cases of plasma cell myeloma and lymphoplasmacytic lymphoma, which may have a similar appearance.
LEUKEMIA CUTISBr J Dermatol 2000;143:773-779
Am J Clin Pathol 1997;107:627-629Vasculitis common feature with extensive infiltration of the vessel walls
A Case of Acantholytic Dermatosis and Leukemia Cutis: Cause or Effect?
Pamela E. Sakalosky, M.D.; Neil Fenske, M.D.; Michael B. Morgan, M.D.
Am J Dermatopathol 2002; 24(3):257-259 Abstract quote
Leukemia cutis is capable of presenting in a variety of clinical and histologic guises. We describe a 75-year-old man with a recent diagnosis of M0 acute myelogenous leukemia, who presented with multiple pruritic erythematous papules on his chest and back. Microscopically, the epidermis showed acrosyringeal-based acantholysis consistent with transient acantholytic dermatosis (TAD), associated with exocytosis of atypical hematolymphoid cells. In addition, the dermis showed a contiguous atypical hematolymphoid proliferation consistent with conventional leukemia cutis.To our knowledge, this is the first such case combining features of TAD with leukemia cutis. It remains to be determined whether the acantholysis occurred secondary to the leukemia cutis, was initiated by the migration of leukemic cells, or if the association is merely serendipitous.
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION PERIPHERAL T-CELL LYMPHOMA Granulocytic sarcoma: an immunohistologic comparison with peripheral T-cell lymphoma in paraffin sections.
Ritter JH, Goldstein NS, Argenyi Z, Wick MR.
Division of Surgical Pathology, Barnes Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
J Cutan Pathol 1994 Jun;21(3):207-16 Abstract quote
In evaluating histologically malignant infiltrates in the skin, it is often challenging to distinguish granulocytic sarcoma (GS) from selected cases of peripheral T-cell lymphoma (PTCL). These lesions have clinical features in common, in addition to shared histologic attributes. These include similarity in dermal distribution and growth pattern, nuclear characteristics, propensity to recruit other inflammatory cell types, and production of matrical sclerosis.
In order to determine if immunohistology could contribute to differential diagnosis in this setting, we analyzed 15 cases of mucocutaneous GS, and compared them with 11 cases of well-documented PTCL. Antibodies in the CD15, CD20, CD34, CD43, CD45, CD45RO, and CD68 groups were used, as well as anti-myeloperoxidase (anti-MPX), anti-lysozyme (anti-LYSO), Mac387, and MB2.
Anti-LYSO and anti-MPX were sensitive and specific markers of GS, labeling 93% and 80% of GS cases, respectively, and no cases of PTCL. Anti-CD15 and MB2 were also specific for GS, but each labeled only 60% of GS cases. CD34, CD68, and Mac 387 were specific but insensitive markers of GS. CD43 and CD45 were not particularly useful discriminants, with each being seen in 93% of GS cases, but also 64% and 100% of cases of PTCL, respectively. CD45RO was specific for PTCL; it was present in 82% of PTCL cases and no GS cases.
Thus, conjoint reactivity for CD43, CD45, MPX, and LYSO characterizes GS, and differs from the pattern of PTCL, which is characterized by reactivity for CD45 and CD45RO, occasional reactivity for CD43, and lack of other specified markers.
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Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
Auer Rods-These are distinct red rod-like structures present within the cytoplasm of some immature myeloid cells. When present in many cells, they may indicate a promyelocytic leukemia, a variant of AML.
Blast Crisis-A transformation of a chronic leukemia to a clinical scenario of an acute leukemia with a proliferation of blasts.
FAB Classification-French-American-British Classification-The most commonly used classification system for acute leukemias. The system utilizes a combination blast morphology as well as the presence of other blood elements, such as erythroblasts.
Relapse-Recurrence of leukemia after a period of remission.
Remission-Eradication of the leukemia cells by chemotherapy or other treatment.
TdT-Terminal deoxytransferase. An enzyme which is helpful in differentiating ALL cases from AML. It is present in 95% of cases of ALL but in less than 5% of cases in AML.
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Last Updated February 25, 2008
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