Highly Aggressive CD4-Positive Mast Cell Leukaemia (Leukaemic Variant) Associated with Isolated Trisomy 19 and Hemophagocytosis by Neoplastic Mast Cells: A Case Report with Challenging Experience and Review

Background. Mast cell leukaemia is a unique disease among hematopoietic neoplasms, being one of the rarest leukaemia subtypes. In addition, its prompt diagnosis is usually challenging. This is due to its heterogeneity in clinical presentations and cytomorphological and immunophenotypical features together with potential associations with other hematologic neoplasms which can complicate the condition and delay accurate diagnosis. To the best of our knowledge, this is the first case report of CD4-positive mast cell leukaemia. Case Presentation. A 39-year-old male presented with acute onset of fever, abdominal pain, and generalized body aches of two-week duration. Peripheral blood smear showed circulating blasts (13%) with coarsely basophilic granulation. Bone marrow (BM) aspirate showed extensive infiltration with immature mast cells of blast-like morphology with trilineage dysplasia and evident hemophagocytic activity exhibited by histiocytes and neoplastic mast cells. BM biopsy was diffusely infiltrated with many atypical mast cells positive for CD45, CD117, mast cell tryptase, CD25, and CD4 with partial positivity for CD7 and CD30. Cytogenetics showed an abnormal karyotype: 47, XY, +1947, XY, +19[13]/46, XY[9]. Molecular analysis revealed a KIT D816V mutation consistent with a diagnosis of systemic mastocytosis, mast cell leukaemia. Conclusion. The expression of T-cell associated markers by abnormal mast cells is well documented; however, CD4 and CD7 expression have not previously been described in association with mast cell leukaemia. Coexpression of CD2, CD4, CD7, and CD30 by the mast cells particularly in skin lesions may provoke misinterpretation as a cutaneous T-cell neoplasm. To the best of our knowledge, this is the first report of CD4-positive mast cell leukaemia. Moreover, hemophagocytic mast cell leukaemia is a very rare morphologic variant, and possible correlation between this finding and expression of CD4 by neoplastic mast cells is a topic for further investigation.

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Imatinib Mesylate in the Treatment of Systemic Mastocytosis, a Phase I/II Trial.

Blood ◽

10.1182/blood.v104.11.1516.1516 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1516-1516 ◽

Cited By ~ 7

Author(s):

H.J. Droogendijk ◽

J.C. Kluin-Nelemans ◽

P.L.A van Daele

Keyword(s):

Bone Marrow ◽

Cell Proliferation ◽

Mast Cell ◽

Mast Cells ◽

Imatinib Mesylate ◽

Systemic Mastocytosis ◽

Skin Lesions ◽

Tissue Response ◽

Serum Tryptase ◽

Kit Receptor

Abstract Introduction: mastocytosis comprimes a group of diseases characterized by abnormal proliferation and accumulation of mast cells in one or more organs. A cutaneous and systemic form of mastocytosis is distinguished. Systemic mastocytosis defines the disease process in which mast cell proliferation exceeds the skin. The clinical manifestations of systemic mastocytosis depend on the tissues involved and the tissue response to the accumulation of mast cells. Although in general the disease progresses slowly, it may develop into a malignant disease. Currently there is no cure for systemic mastocytosis. Mast cells develop from pluripotent bone marrow progenitor cells that express CD34 antigen and are dispersed as precursors which undergo proliferation and maturation in different tissues. Normal mast cell development involves the action of stam cell growth factor and c-kit receptors, which are expressed by mast cells at their different developmental stages. Deregulation and/or abnormalities of the c-kit receptor are assumed to play a causal role in disordered mast-cell proliferation. In most patients a mutation in the gene for c-kit exists. One of the mutations is the D816V mutation. Aim of the study:imatinib mesylate, formerly called ST1571, is a potent inhibitor of c-kit receptor tyrosine kinase activity. In this study, we evaluate whether imatinib mesylate is safe and effective in the treatment of patients with systemic mastocytosis. Primary end-points of study are reduction in urinary N-methylhistamine excretion, serum tryptase activity, skin lesions, number of mast cells in sections of bone marrow, hepato-and/or splenomegaly and symptoms.Adverse effects on therapy are also considered. Results: up to now, 10 patients with systemic mastocytosis are treated with 400 mg of imatinib mesylate orally once daily. During the first 2 weeks of the study the patients also received 30 mg of prednisolone daily. In general imatinib mesylate is well tolerated. The first results show a 38–80% reduction in urinary N-methylhistamine excretion and 30–66% reduction in serum tryptase activity. Skin lesions diminish in two of the six patients with cutaneous mastocytosis,. Number of mast cells in sections of bone marrow are reduced in 63% (5/8) of the patients. Hepato-and/or splenomegaly is slightly decreased in two of the three patients with organomegaly. Finally 60 % of all patients experiences relief of symptoms. In eight patients the D816V mutation was found. In contrast with former studies imatinib mesylate is also effective in these patients. Further results are to be awaited. Conclusion: imatinib mesylate is safe and seems effective in the treatment of patients with systemic mastocytosis (including patients with the D816V mutation).

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Clinical, Biological, and Molecular Characteristics of Well-Differentiated Systemic Mastocytosis: a study in 18 Patients by Spanish Network on Mastocytosis (REMA)

Blood ◽

10.1182/blood.v112.11.5246.5246 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5246-5246

Author(s):

Iván Alvarez-Twose ◽

Laura Sánchez-Muñoz ◽

María Jara-Acevedo ◽

Cristina Teodosio ◽

Andrés García-Montero ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Systemic Mastocytosis ◽

Skin Lesions ◽

Categorical Variables ◽

Molecular Characteristics ◽

Skin Involvement ◽

Serum Tryptase ◽

Kit Mutation ◽

Well Differentiated

Abstract BACKGROUND: Well-differentiated systemic mastocytosis (WDSM) has recently been described as a novel form of mast cell disease. WDSM is characterized by a marked increase of bone marrow (BM) mast cells, usually with compact aggregates, with normal phenotype and morphology as well as the absence of the typical D816V somatic KIT mutation. OBJECTIVE: To describe and compare clinical, morphological, biological and molecular characteristics in a group of 18 patients who fullfilled criteria for WDSM with a group of 32 patients with indolent systemic mastocytosis (ISM). PATIENTS AND METHODS: All the patients were diagnosed on the basis of BM aspirate and biopsy findings after they were thought to have a systemic mastocytosis. A rigorous skin examination together with a clinical work-up and a complete laboratory analysis including peripheral blood count, routine biochemistry and serum tryptase levels were performed. The Mann-Whitney U and the chi-square tests were used to assess the statistical differences of continuous and categorical variables, respectively. RESULTS: WDSM patients were 4 males and 14 females with a median (range) age of 24 years (2–72) at diagnosis. Median (range) age at the time of the first observation of skin lesions was 2 years (0–41). In 16 of the 18 patients (89%), skin lesions appeared under the age of 14, five of them being younger than 1 year old. All the WDSM patients had skin involvement but the typical maculo-papular lesions were found only in 18% of patients while in the remaining 82% of cases, cutaneous lesions were plaques or nodules. Interestingly, 78% of WDSM patients had cutaneous neck involvement in contrast with only 13% in the ISM group (p<0.001). There were no significant differences in mast cell mediators-related symptoms such as pruritus, flushing, abdominal pain or diahrrea between the two groups while anaphylactic reactions were significantly more frequent in the WDSM group than in the ISM group (59% vs 19%, p=0.004). Overall, bone loss was found in 38% and 37% of WDSM and ISM patients, respectively. Among all the biochemical parameters analyzed, only median serum cholesterol (mg/dL), ferritin (ng/mL) and tryptase levels (ng/mL) were significantly lower in patients with WDSM when compared to ISM patients (150 vs 168.5, p=0.043; 31.3 vs 56.6, p=0.004; 11 vs 31.6, p<0.001; respectively). There were no significant differences in the median percentage of mast cells in the BM study as assesed by flow cytometry between both groups (0.055% in WDSM group and 0.08% in ISM group). In contrast, the presence of both fibrosis and lymphoid aggregates in the BM biopsy were more frequent in patients with ISM than in patients with WDSM (52% vs 0%, p<0.001; 55% vs 14%, p=0.01; respectively). Somatic KIT mutation at codon 816 was found in 31 of the 32 ISM patients (97%) while only in one (6%) WDSM patient (p<0.001). Additionally, 2 WDSM patients were found to carry variant mutations at codons other than at codon 816 (N819Y and I817V, respectively). From the remaining 15 WDSM patients, clonality of mast cell population was demonstrated by human androgen receptor (HUMARA) assay in the 5 female patients in whom the assay was made. CONCLUSIONS: WDSM is a variant of systemic mastocytosis with several characteristics that are distinguishable from ISM, such as: early onset of skin lesions, atypical skin involvement (plaques or nodules and cutaneous neck involvement), frequent anaphylactic episodes, lower serum tryptase levels than ISM despite no differences in BM mast cell infiltration, and infrequent detection of typical activating D816V KIT mutation.

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Serum Total Tryptase Level Confirms Itself as a More Reliable Marker of Mast Cells Burden in Mast Cell Leukaemia (Aleukaemic Variant)

Case Reports in Hematology ◽

10.1155/2015/737302 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4

Author(s):

P. Savini ◽

M. Rondoni ◽

G. Poletti ◽

A. Lanzi ◽

O. Quercia ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Systemic Mastocytosis ◽

Organ Damage ◽

High Serum ◽

Cell Leukaemia ◽

Cell Leukemia ◽

Tryptase Level ◽

Mast Cell Leukemia ◽

Reliable Marker

Mast cell leukemia (MCL) is a very rare form of systemic mastocytosis (SM) with a short median survival of 6 months. We describe a case of a 65-year-old woman with aleukaemic variant of MCL with a very high serum total tryptase level of 2255 μg/L at diagnosis, which occurred following an episode of hypotensive shock. She fulfilled the diagnostic criteria of SM, with a bone marrow smear infiltration of 50–60% of atypical mast cells (MCs). She tested negative for the KIT D816V mutation, without any sign of organ damage (no B- or C-findings) and only few mediator-related symptoms. She was treated with antihistamine alone and then with imatinib for the appearance of anemia. She maintained stable tryptase level and a very indolent clinical course for twenty-two months; then, she suddenly progressed to acute MCL with a serum tryptase level up to 12960 μg/L. The patient died due to haemorrhagic diathesis twenty-four months after diagnosis. This clinical case maybe represents an example of the chronic form of mast cell leukemia, described as unpredictable disease, in which the serum total tryptase level has confirmed itself as a reliable marker of mast cells burden regardless of the presence of other signs or symptoms.

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Successful extracorporeal membrane oxygenation resuscitation of patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism: A case report

Open Life Sciences ◽

10.1515/biol-2021-0073 ◽

2021 ◽

Vol 16 (1) ◽

pp. 746-751

Author(s):

Tao Wang ◽

Qiancheng Xu ◽

Xiaogan Jiang

Keyword(s):

Case Report ◽

Extracorporeal Membrane Oxygenation ◽

Cardiogenic Shock ◽

Tumour Size ◽

Acute Onset ◽

Left Ventricular ◽

Vanillylmandelic Acid ◽

Membrane Oxygenation ◽

First Case ◽

Va Ecmo

Abstract A 29-year-old woman presented to the emergency department with the acute onset of palpitations, shortness of breath, and haemoptysis. She reported having an abortion (56 days of pregnancy) 1 week before admission because of hyperthyroidism diagnosis during pregnancy. The first diagnoses considered were cardiomyopathy associated with hyperthyroidism, acute left ventricular failure, and hyperthyroidism crisis. The young woman’s cardiocirculatory system collapsed within several hours. Hence, venoarterial extracorporeal membrane oxygenation (VA ECMO) was performed for this patient. Over the next 3 days after ECMO was established, repeat transthoracic echocardiography showed gradual improvements in biventricular function, and later the patient recovered almost completely. The patient’s blood pressure increased to 230/130 mm Hg when the ECMO catheter was removed, and then the diagnosis of phaeochromocytoma was suspected. Computed tomography showed a left suprarenal tumour. The tumour size was 5.8 cm × 5.7 cm with central necrosis. The vanillylmandelic acid concentration was 63.15 mg/24 h. Post-operation, pathology confirmed phaeochromocytoma. To our knowledge, this is the first case report of a patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism which was successfully resuscitated by VA ECMO.

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Scabies superimposed on skin lesions of adult T-cell leukemia/lymphoma: case report and literature review

International Journal of Dermatology ◽

10.1111/j.1365-4632.2008.03707.x ◽

2008 ◽

Vol 47 (11) ◽

pp. 1168-1171 ◽

Cited By ~ 5

Author(s):

Rieko Kabashima ◽

Kenji Kabashima ◽

Ryosuke Hino ◽

Takatoshi Shimauchi ◽

Yoshiki Tokura

Keyword(s):

Case Report ◽

T Cell ◽

Literature Review ◽

Skin Lesions ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia

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The Mote in thy Brother’s Eyes - Fusarium Solani in Leukemia Host

10.21203/rs.3.rs-787465/v1 ◽

2021 ◽

Author(s):

Rawan AlAgha ◽

Wee Lee Chan ◽

Thong Edwin Wei Sheng ◽

Joanne Lee ◽

Jen Wei Ying ◽

...

Keyword(s):

Case Report ◽

Early Diagnosis ◽

High Mortality ◽

Combination Chemotherapy ◽

Fusarium Solani ◽

Immunocompromised Host ◽

Skin Lesions ◽

Acute Onset ◽

Source Control ◽

Anti Fungal

Abstract Fusariosis is increasingly seen among immunocompromised host. The organism is known for its virulence and spectrum of infections. Presenting here a case of relapse acute myeloblastic leukemia on chemotherapy with acute onset of red painful eye followed by widespread painful skin lesions. Microbiological and radiological investigations diagnosed her with disseminated fusariosis. Treatment was challenging in view its inherent resistance to multiple anti-fungal agents and the need for early aggressive source control. The case report reflects the importance of early diagnosis and combination chemotherapy to salvage the patient from high mortality.

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MDS with 5q deletion and rare cKIT positive mastocytosis: a diagnostic and therapeutic challenge

BMJ Case Reports ◽

10.1136/bcr-2018-227768 ◽

2019 ◽

Vol 12 (4) ◽

pp. e227768

Author(s):

Daniel Steven Sanders ◽

Thomas Fennell ◽

Mohammad Muhsin Chisti

Keyword(s):

Bone Marrow ◽

Mast Cell ◽

Case Report ◽

Systemic Mastocytosis ◽

Molecular Testing ◽

Bone Marrow Biopsies ◽

Haematological Response ◽

Clonal Origin ◽

Mast Cell Population ◽

5Q Deletion

A patient with a diagnosis of myelodysplastic syndrome (MDS) with isolated 5q deletion underwent repeat bone marrow biopsy to assess haematological response after 6 months of initial lenalidomide therapy. Subsequent bone marrow biopsies revealed persistent MDS with del(5q) in addition to a small atypical mast cell population with >25% of mast cells with spindle-shaped morphology and immunohistochemistry characteristics consistent with mastocytosis. Molecular testing on the bone marrow was positive for cKIT D816V and the patient was diagnosed with systemic mastocytosis (SM) with an associated haematological neoplasm. MDS with SM is well known to be associated; however, to the best of our knowledge, only one prior case report identifies MDS with del(5q) and associated cKIT D816V positive mastocytosis. While the exact clonal origin of both chromosomal aberrations is unclear, this case illustrates the therapeutic efficacy of lenalidomide in a patient with MDS with del(5q) and rarely associated cKIT positive SM.

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Systemic mastocytosis with subcutaneous hemorrhage and edema in a Greyhound dog: case report and review of diagnostic criteria

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638720972500 ◽

2020 ◽

Vol 33 (1) ◽

pp. 95-100

Author(s):

Alexander Aceino ◽

Unity Jeffery ◽

Julie Piccione ◽

Carolyn L. Hodo

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Diagnostic Criteria ◽

Complete Blood Count ◽

Systemic Mastocytosis ◽

Mast Cell Tumors ◽

Multiple Organs ◽

Subcutaneous Edema ◽

Diagnostic Framework ◽

Criteria For Diagnosis

Systemic mastocytosis, characterized by infiltration of multiple organs by neoplastic mast cells, is a well-described entity in human medicine with specific criteria for diagnosis, but is ill defined in veterinary literature. Hemostatic disorders are reported in humans affected by systemic mastocytosis but have not been well described in veterinary literature. A 5-y-old, spayed female Greyhound dog had a 1-mo history of progressive ventral cutaneous edema, hemorrhage, and pain. Cytology of an antemortem aspirate from the subcutis of the ventral abdomen was suggestive of mast cell neoplasia, but no discrete mass was present. The dog was euthanized and submitted for autopsy; marked subcutaneous edema and hemorrhage were confirmed. The ventral abdominal panniculus and dermis superficial to the panniculus carnosus were infiltrated by a dense sheet of neoplastic mast cells. The neoplastic cells contained toluidine blue–positive granules and formed aggregates within the bone marrow and several visceral organs, including the liver, spleen, heart, and kidney. Diffuse edema and hemorrhage is an unusual presentation of mast cell tumors in dogs. Antemortem tests, including complete blood count, coagulation profile, and viscoelastic coagulation testing, were suggestive of a primary hemostatic defect. We discuss here the diagnostic criteria used in humans, how these can be applied to veterinary patients, and the limitations of the current diagnostic framework.

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