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Scheda a cura di Marco Chilosi  (GYM)  

MASTOCITOSI 

La mastocitosi è un processo neoplastico caratterizzato dalla proliferazione di mastociti. 

Esistono diversi tipi di mastocitosi, caratterizzati da differente coinvolgimento tissutale (forme cutanee, forme sistemiche) e da diversa aggressività clinica.

La WHO descrive le seguenti forme:

       La mastocitosi viene nella maggior parte dei casi diagnosticata su biopsia cutanea o su biopsia osteomidollare.  

La sintomatologia e i dati ematologici nelle forme sistemiche possono essere molto vari, e possono sviare il processo diagnostico (ad es. si può avere piastrinopenia o piastrinosi, eosinofilia marcata, anemia, fino all'insufficienza midollare). 

La diagnosi istologica di mastocitosi si basa sul riscontro di aggregati di mastociti. L'identificazione qualitativa e quantitativa degli aggregati (spesso multifocali) è resa più attendibile dall'impiego di colorazioni speciali (Giemsa, toluidine-blue, colorazione per Cloroacetato esterasi) o, preferibilmente, di marcatori immunoistologici. 

Spesso infatti negli aggregati della mastocitosi, le MC assumono forme bizzarre, spesso fusate e non sono facilmente riconoscibili. Anche le colorazioni speciali possono essere poco significative quando i mastociti siano poco granulati (spesso infatti nelle forme meno mature la metacromasia non è evidente), ed il citoplasma appare chiaro (possibile confusione con hairy cell leukemia, fibroblasti o istiociti).

PATOGENESI e CD117

Caso 1. Paziente con mastocitosi cutanea. Biopsia osteomidollare.

Si evidenziano aggregati paratrabecolari e perivascolari di mastociti

E&E

Giemsa

Significativa espressione di Mast cell tryptase

  Intensa espressione di CD117 negli aggregati di mastociti 

Gli aggregati di mastociti sono spesso associati a un infiltrato linfoide B

CD20+

References

Hum Pathol 2001 May;32(5):545-52

Immunohistochemical properties of bone marrow mast cells in systemic mastocytosis: evidence for expression of CD2, CD117/Kit, and bcl-x(L).

Jordan JH, Walchshofer S, Jurecka W, Mosberger I, Sperr WR, Wolff K, Chott A, Buhring HJ, Lechner K, Horny HP, Valent P.

Department of Internal Medicine I, Division of Hematology and Hemostaseology, University of Vienna, Vienna, Austria.

In an attempt to identify novel diagnostic markers for mast cell (MC)-proliferative disorders, serial bone marrow (bm) sections of 22 patients with mastocytosis (systemic indolent mastocytosis, n = 19; mast cell leukemia [MCL], n = 1; isolated bm mastocytosis, n = 2) were analyzed by immunohistochemistry using antibodies against CD2, CD15, CD29, CD30, CD31, CD34, CD45, CD51, CD56, CD68R, CD117, HLA-DR, bcl-2, bcl-x(L), myeloperoxidase (MPO), and tryptase. Staining results revealed expression of bcl-x(L), CD68R, and tryptase in neoplastic MCs (focal dense infiltrates) in all patients. Mastocytosis infiltrates were also immunoreactive for CD45, CD117 (Kit), and HLA-DR. In most cases, the CD2 antibody produced reactivity with bm MCs in mastocytosis, whereas in control cases (reactive bm, immunocytoma, myelodysplastic syndrome), MCs were consistently CD2 negative. Expression of bcl-2 was detectable in a subset of MCs in the patient with MCL, whereas no reactivity was seen in patients with SIM or bm mastocytosis. Mastocytosis infiltrates did not react with antibodies against CD15, CD30, CD31, CD34, or MPO. In summary, our data confirm the diagnostic value of staining for tryptase, Kit, and CD68R in mastocytosis. Apart from these, CD2 may be a novel useful marker because MCs in mastocytosis frequently express this antigen, whereas MCs in other pathologic conditions are CD2 negative.

 

Leuk Res 2001 Jul;25(7):543-51

Diagnosis of mastocytosis: general histopathological aspects, morphological criteria, and immunohistochemical findings.

Horny HP, Valent P.

Institute of Pathology, Medical University of Lubeck, Ratzeburger Allee 160, D-23538 Lubeck, Germany. horny@patho.mu-luebeck.de

An increase in mast cell (MC) numbers in hemopoietic tissues may be associated with (a) primary neoplastic MC disease (mastocytosis); (b) non-mast cell lineage myelogenous disorders (myelodysplastic or myeloproliferative syndromes and myeloid leukemias); or (c) reactive, i.e. non-clonal states (MC hyperplasia and reactive mastocytosis). However, the histologic discrimination between hyperplastic states and neoplastic MC proliferative disorders is sometimes very difficult. MC hyperplasia is characterized by a diffuse increase in mature, round or spindle-shaped, metachromatic MC that are loosely scattered throughout the tissue and do not form dense focal infiltrates, even in states of marked hyperplasia. However, loosely scattered MC are also a prominent feature of many cases of myelodysplastic syndromes and acute leukemia involving the MC lineage. In contrast, the demonstration of dense, focal and/or diffuse MC infiltrates can be regarded as indicative of primary MC disease/mastocytosis. In addition to the highly diagnostic focal MC infiltrates, mastocytosis may also present with a predominantly diffuse or a mixed (diffuse and focal) infiltration pattern. The relatively rare diffuse pattern is usually dominated by atypical, often hypogranulated or even non-metachromatic MC and is associated with the aggressive or frankly malignant subtypes of systemic mastocytosis and MC leukemia. Although the demonstration of MC infiltrates in Giemsa-stained tissue sections is still very important for the diagnosis of mastocytosis, immunohistochemical techniques using antibodies against MC-associated antigens such as tryptase or c-kit (CD117) are essential for the identification of highly atypical, hypogranulated MC, especially in MC leukemia, and for the detection of small and even minute MC infiltrates.

 

Am J Surg Pathol 2000 May;24(5):703-9

Paraffin section immunophenotype of cutaneous and extracutaneous mast cell disease: comparison to other hematopoietic neoplasms.

Yang F, Tran TA, Carlson JA, Hsi ED, Ross CW, Arber DA.

Division of Pathology, City of Hope National Medical Center, Duarte, California 91010, USA.

Mast cell disease (MCD) is a rare proliferation that may be easily confused with other hematopoietic tumors. Several paraffin section antibodies immunoreact with mast cells but most are not specific. Tryptase, a specific marker of mast cells, may not be cost-effective to maintain in a laboratory because of the rarity of these lesions. This study was undertaken to assess the immunoreactivity of MCD and attempt to select a limited antibody panel for diagnosing MCD among hematopoietic tumors that morphologically mimic MCD. Immunophenotyping of cutaneous ( 10 cases) and extracutaneous (18 cases) MCD, as well as 94 other hematopoietic neoplasms, was performed on paraffin sections. All cases of MCD showed strong and diffuse positivity for CD68 and tryptase. In the vast majority of the cases, the mast cells were also positive for CD117 (27 of 28) and CD43 (25 of 27). Four cases (40%) of cutaneous MCD demonstrated a subpopulation of mast cells expressing myeloperoxidase (MPX), whereas all extracutaneous MCD were negative for MPX. Two (40%) extramedullary myeloid tumors (EMT) expressed CD43, CD68, CD 117, and MPX, but none expressed tryptase. CD43, CD68, CD117, and tryptase were expressed by 25%, 1%, 15%, and 1%, respectively, of all B-cell lymphoid neoplasms, and none expressed more than one of these four antigens. We conclude that (1) cutaneous MCDs may demonstrate a subpopulation of MPX antigen expressing tumor cells and may be confused with cutaneous involvement by myeloid leukemia if other antibodies are not used; (2) tryptase is the most specific mast cell marker among the antibodies studied; and, (3) the detection of tryptase, together with CD68, CD117, and usually CD43, is unique to MCD among hematopoietic tumors.

 

Am J Surg Pathol 2000 Jan;24(1):81-91

Utility of paraffin section immunohistochemistry for C-KIT (CD117) in the differential diagnosis of systemic mast cell disease involving the bone marrow.

Natkunam Y, Rouse RV.

Department of Pathology, Stanford University Medical Center, CA 94305, USA.

Systemic mast cell disease is characterized by an abnormal infiltration of mast cells involving several parenchymal organs and the bone marrow. Its spectrum of clinical and histologic presentation is highly variable and is not necessarily correlated with prognosis. Mast cell disorders presenting as atypical infiltrates in the bone marrow may simulate or be associated with other hematolymphoid malignancies, from which they must be distinguished. The paucity of reliable histochemical and immunohistochemical markers for the detection of mast cells in paraffin sections further confounds this diagnosis. The authors have employed immunohistochemistry for the C-KIT encoded tyrosine kinase receptor protein, CD117, for detection of mast cells on paraffin sections of 89 bone marrow specimens including systemic mast cell disease and other disorders. CD117 staining was found in all cases of mast cell disorders (seven of seven), and in one case of chronic myelogenous leukemia in blast crisis. None of the other myeloid disorders tested (0 of 16), or any of the cases of Hodgkin's disease (0 of 12), B-cell lymphomas (0 of 32), T-cell lymphomas (0 of 3), or histiocytic proliferations (0 of 3) showed staining for CD117. CD117 expression is effective in the separation of mast cell disease from disorders that may simulate it histologically.

 

Leuk Res 2001 Jul;25(7):603-25

Diagnostic criteria and classification of mastocytosis: a consensus proposal.

Valent P, Horny HP, Escribano L, Longley BJ, Li CY, Schwartz LB, Marone G, Nunez R, Akin C, Sotlar K, Sperr WR, Wolff K, Brunning RD, Parwaresch RM, Austen KF, Lennert K, Metcalfe DD, Vardiman JW, Bennett JM.

Department of Internal Medicine I, Division of Hematology, University of Vienna, Wahringer Gurtel 18-20 Vienna, Austria. peter.valent@akh-wien.ac.at

The term 'mastocytosis' denotes a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MC) in one or more organ systems. Over the last 20 years, there has been an evolution in accepted classification systems for this disease. In light of such developments and novel useful markers, it seems appropriate now to re-evaluate and update the classification of mastocytosis. Here, we propose criteria to delineate categories of mastocytosis together with an updated consensus classification system. In this proposal, the diagnosis cutaneous mastocytosis (CM) is based on typical clinical and histological skin lesions and absence of definitive signs (criteria) of systemic involvement. Most patients with CM are children and present with maculopapular cutaneous mastocytosis (=urticaria pigmentosa, UP). Other less frequent forms of CM are diffuse cutaneous mastocytosis (DCM) and mastocytoma of skin. Systemic mastocytosis (SM) is commonly seen in adults and defined by multifocal histological lesions in the bone marrow (affected almost invariably) or other extracutaneous organs (major criteria) together with cytological and biochemical signs (minor criteria) of systemic disease (SM-criteria). SM is further divided into the following categories: indolent systemic mastocytosis (ISM), SM with an associated clonal hematologic non-mast cell lineage disease (AHNMD), aggressive systemic mastocytosis (ASM), and mast cell leukemia (MCL). Patients with ISM usually have maculopapular skin lesions and a good prognosis. In the group with associated hematologic disease, the AHNMD should be classified according to FAB/WHO criteria. ASM is characterized by impaired organ-function due to infiltration of the bone marrow, liver, spleen, GI-tract, or skeletal system, by pathologic MC. MCL is a 'high-grade' leukemic disease defined by increased numbers of MC in bone marrow smears (>or=20%) and peripheral blood, absence of skin lesions, multiorgan failure, and a short survival. In typical cases, circulating MC amount to >or=10% of leukocytes (classical form of MCL). Mast cell sarcoma is a unifocal tumor that consists of atypical MC and shows a destructive growth without (primary) systemic involvement. This high-grade malignant MC disease has to be distinguished from a localized benign mastocytoma in either extracutaneous organs (=extracutaneous mastocytoma) or skin. Depending on the clinical course of mastocytosis and development of an AHNMD, patients can shift from one category of MC disease into another. In all categories, mediator-related symptoms may occur and may represent a serious clinical problem. All categories of mastocytosis should be distinctively separated from reactive MC hyperplasia, MC activation syndromes, and a more or less pronounced increase in MC in myelogenous malignancies other than mastocytosis. Criteria proposed in this article should be helpful in this regard.