Scholarly article on topic 'Diffuse large B cell lymphoma coexistence with systemic mastocytosis'

Diffuse large B cell lymphoma coexistence with systemic mastocytosis Academic research paper on "Clinical medicine"

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{"Diffuse large B cell lymphoma" / "Systemic mastocytosis" / "Systemic mastocytosis associated with a clonal non-mast cell lineage" / Tryptase / "KIT mutation"}

Abstract of research paper on Clinical medicine, author of scientific article — Sheng-Hsuan Chien, Yao-Chung Liu, Ying-Chung Hong, Ching-Fen Yang, Chun-Yu Liu, et al.

Abstract Systemic mastocytosis is a rare disease and characterized by excessive mast cell accumulation in one or multiple organs. One subtype of systemic mastocytosis is systemic mastocytosis-associated clonal hematological non-mast cell lineage disease (SM-AHMND), which indicates concurrent evolution of two separate clonal entities, one consisting of mast cells and one as a second hematological as well as non-mast cell origin disease. When SM-AHMND is diagnosed, bone marrow examination is essential for the initial approach, because marrow is almost universally involved in adult mastocytosis and it facilitates detection of a second hematological neoplasm. Myeloid neoplasm is reported to be the most prevalent associated clonal hematological non-mast cell disease. Treatment strategy and outcome for SM-AHMND is dependent on hematological non-mast cell lineage disease. Herein, we have presented a case report of diffuse large B cell lymphoma coexisting with systemic mastocytosis where the patient underwent successful chemotherapy leading to extended survival duration.

Academic research paper on topic "Diffuse large B cell lymphoma coexistence with systemic mastocytosis"

Journal of Cancer Research and Practice xxx (2016) 1—4

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Journal of Cancer Research and Practice

journal homepage: http://www.journals.elsevier.com/journal-of-cancer-

research-and-practice

Case report

Diffuse large B cell lymphoma coexistence with systemic mastocytosis

Sheng-Hsuan Chien a'b'c'd, Yao-Chung Liu b'd, Ying-Chung Hong b'e, Ching-Fen Yang f, Chun-Yu Liu b'g, Tzeon-Jye Chiou b'h Jyh-Pyng Gau b,d *

Cheng-Hwai Tzeng b'd, Jin-Hwang Liu b'd,

a Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taitung Branch, Taitung City, Taitung County, Taiwan

b Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan

c Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

d Division of Hematology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

e Division of Hematology and Oncology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

f Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

g Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan

h Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

ARTICLE INFO

Article history: Received 15 July 2015 Accepted 21 September 2015 Available online xxx

Keywords:

Diffuse large B cell lymphoma

Systemic mastocytosis

Systemic mastocytosis associated with a

clonal non-mast cell lineage

Tryptase

KIT mutation

ABSTRACT

Systemic mastocytosis is a rare disease and characterized by excessive mast cell accumulation in one or multiple organs. One subtype of systemic mastocytosis is systemic mastocytosis-associated clonal hematological non-mast cell lineage disease (SM-AHMND), which indicates concurrent evolution of two separate clonal entities, one consisting of mast cells and one as a second hematological as well as nonmast cell origin disease. When SM-AHMND is diagnosed, bone marrow examination is essential for the initial approach, because marrow is almost universally involved in adult mastocytosis and it facilitates detection of a second hematological neoplasm. Myeloid neoplasm is reported to be the most prevalent associated clonal hematological non-mast cell disease. Treatment strategy and outcome for SM-AHMND is dependent on hematological non-mast cell lineage disease. Herein, we have presented a case report of diffuse large B cell lymphoma coexisting with systemic mastocytosis where the patient underwent successful chemotherapy leading to extended survival duration.

Copyright © 2016, The Chinese Oncology Society. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction

Mastocytosis indicates a group of disorders characterized by excessive mast cell accumulation in one or multiple organs and is a type of myeloproliferative neoplasm disorder, according to the 2008 World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues Non-Hodgkin lymphoma.1 Mastocytosis is heterogeneous and can involve multiple sites, ranging from skin lesions, which may spontaneously resolve to highly aggressive mast cell leukemia associated with multiple organ failure. It is a rare disease and its exact incidence is unknown. Subtypes of mastocytosis are recognized primarily through clinical

* Corresponding author. Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.

E-mail address: jpgau@vghtpe.gov.tw (J.-P. Gau).

Peer review under responsibility of The Chinese Oncology Society.

presentation and distribution of disease. Mast cell infiltration confined to the skin is cutaneous mastocytosis, whereas systemic mastocytosis (SM) is regarded as involvement of at least one extra-cutaneous organ with or without the presence of skin lesions.2 Clinically, SM is classified as indolent SM (ISM), aggressive SM (ASA), SM with associated clonal hematological non-mast cell lineage disease (SM-AHMND), and mast cell leukemia (MCL).1 ISM, the most common subgroup among SM, usually refers to symptoms resulting from mast cell degranulation, mediator release, allergies or anaphylaxis and no evidence of extra-cutaneous organ dysfunction or failure,3 while ASM indicates the presence of extra-cutaneous organ dysfunction or failure caused by mast cell infil-tration.4 On the other hand, SM-AHNMD is the second most common SM subgroup and myeloid neoplasm is reported most frequently as hematological non-mast cell lineage disease.3 Bone marrow (BM) examination is suggested as part of the initial diagnostic work-up for SM, because BM is almost universally involved in adult mastocytosis. Furthermore, BM examination also allows for

http://dx.doi.org/10.1016/j.jcrpr.2015.09.001

2311-3006/Copyright © 2016, The Chinese Oncology Society. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

S.-H. Chien et al. / Journal of Cancer Research and Practice xxx (2016) 1—4

the detection of a second hematological neoplasm. Since SM is an uncommon disease, SM coexistent with lymphoid neoplasm is extremely rare. Here, we present an interesting case of SM coexistent with diffuse large B cell lymphoma (DLBCL).

2. Case report

A 51-years-old man visited our hospital presenting with a palpable mass over the right inguinal area which had persisted for 3 months. This lesion was approximately 3—4 cm, firm and had progressively enlarged. Laboratory data showed no remarkable anomaly except elevated lactate dehydrogenase (265 U/L). The patient denied experiencing any significant weight loss, poor appetite, night sweats, or sustained fever. After discussing his circumstances with the hematologist in our outpatient department, the patient agreed to undergo surgical excision biopsy. Subsequent histological analysis revealed DLBCL and he underwent further computed tomography with contrast, and BM examination for complete staging. The computed tomography showed right lumbar, iliac and right inguinal lymphoadenopathies, and his clinical Ann Arbor staging was designated as stage II. Further BM examination disclosed diffuse proliferation of large atypical CD20-positive lymphoid cells using hematoxylin and eosin staining (Fig. 1) and immune-histochemical stain (Fig. 2). This is compatible with diffuse large B cell lymphoma, and the patient's staging was upgraded to stage IV. However, at the low power field of 40X, multiple well-circumscribed aggregates of polygonal cells with pale cytoplasm were observed in the bone marrow. At the high power field designation of 200X, these cells were oval to spindle-shaped and contained a moderate amount of pale cytoplasm (Fig. 3), which showed positive for tryptase (Fig. 4) and CD25 (Fig. 5) through immune-histochemical evaluation. The picture was compatible with systemic mastocytosis with associated clonal he-matological non-mast cell lineage disease. Thus, the final diagnosis for this male patient was DLBCL, with right lumbar, iliac and right inguinal lymphoadenopathies and BM involvement, Ann Arbor stage IVA, International Prognostic Index 3, coexisting with SM. In March 2013 he began a course of immune chemotherapy with rituximab, cyclophosphamide, vincristine and prednisolone (R—CHOP), which was the standard treatment for DLBCL. The treatment consisting of 6 courses of R—CHOP was completed in September 2013, and a follow-up integrated Positron emission tomography and computerized tomography (PET-CT) scan revealed

Fig. 2. CD-20 immuno-histochemical stain demonstration on diffuse large B cell lymphoma.

Fig. 3. Mast cell aggregation and infiltration, these cells were oval to spindle-shaped and containing moderate amount of pale cytoplasm.

Fig. 1. Diffuse large B cell lymphoma with bone marrow involvement in hematoxylin and eosin stain.

Fig. 4. Tryptase stain demonstration on mast cell.

nearly complete remission of DLBCL. The port-A was removed in April 2015, as scheduled, and the patient was followed-up regularly in the outpatient department presenting in routine stable condition.

S.-H. Chien et al. / Journal of Cancer Research and Practice xxx (2016) 1—4 3

Fig. 5. CD-25 immuno-histochemical stain demonstration on mast cell.

3. Discussion

Although mastocytosis is a rare disease, it may occur in any age and its presentation is can vary with age. Cutaneous mastocytosis is most common in children, while SM is usually diagnosed in patients > 20 years of age.5 According to the WHO classification, the major criterion for SM diagnosis is that multifocal, dense infiltrates of mast cells (>15 mast cells in aggregates) are detected in sections of bone marrow and/or other extra-cutaneous organs. The other minor criteria for diagnosis are based on either mast cell morphology, genetic mutation at codon 816 of KIT, detection of surface markers of CD2 and/or CD25 or serum total tryptase. Successfully documented diagnosis for SM needs to meet the major criterion and one of minor criteria, or three of minor criteria (Table 1). Recent study revealed mastocytosis was associated with somatic gain-of-function point mutation within KIT tyrosine kinase domain, particularly the D816V mutation6,7 and it has been regard as minor criterion for diagnosis, irrespective of WHO SM subtype. Another important approach tool is tryptase, which can be detected in both mast cell or serum, and elevated serum tryptase level > 20 ng/ml; however, this is also regarded as a minor criterion for SM diagnosis in WHO framework. One earlier study disclosed that ASM and SM-AHNMD patients exhibited a higher level of serum tryptase (usually > 200 ng/ml) than those with ISM.3 Of note, serum tryptase levels are also elevated in certain hematological diseases, such as acute myeloid leukemia, chronic myeloid leukemia and myelodysplastic syndrome.8 BM examination is undoubtedly most essential for the study of both SM and lymphoma for staging, because BM is almost universally involved in adult mas-tocytosis. Berezowska et al had reviewed 59 adults with initial presentation of skin mastocytosis and 57 (96%) of whom were eventually diagnosed with SM by further bone marrow examination. In that study, 42 (71%) subjects met the major criterion and

one minor criterion, while the other 15 (25%) met three of the minor criteria.9ln addition, BM examination also allows for detection of a second hematological neoplasm. In this case presentation, diagnosis of SM was obtained from BM examination for DLBCL staging and involving SM-AHMND.

Chronic myelomonocytic leukemia has been reported as the most prevalent concomitant hematological neoplasm, followed by myelodysplastic, myeloproliferative syndrome, and acute myeloid leu-kemia10; on the other hand, Lymphoproliferative neoplasms were less frequency associated with SM-AHMND.7 In another retrospective study of 342 consecutive patients with SM at the Mayo Clinic extending from 1976 to 2007, their investigation demonstrated that the proportion of SM in lSM, SM-AHMND, ASM, and mast cell leukemia is 46%, 40%, 12% and 1%, respectively.3 Regarding SM-AHMND, 123 (89%) were associated with myeloid neoplasm, while the remainder were lymphoma (n = 7), myeloma (n = 5), chronic lymphocytic leukemia (n = 2), or primary amyloidosis (n = 1). The subclassification of SM-AHMND associated with myeloid neoplasm was as follows: 55 (45%) myeloproliferative neoplasm, 36 (29%) chronic myelomonocytic leukemia, 28 (23%) myelodysplastic syndrome and 4 (3%) acute leukemia. Although lymphoid neoplasms were less frequently associated with SM-AHMND, in the case of lymphoid malignancies, almost all B cell neoplasms may develop currently with SM.10 This phenomenon may be attributed to interactions between the B cell neoplasms and mast cells. One study based on patient pathological findings suggested that angiogenesis and mast cell density with tryptase activity would increase simultaneously pathological progression in B cell non-Hodgkin's lymphomas.11 For ISM treatment, managing histamine symptoms such as anaphylaxis, pruritus, malabsorption, and flashing could be achieved by interferon-alpha, corticosteroids, and cytoreductive therapies, such as cladribine.4 The small-molecule kinase inhibitors, such as imati-nib, have yielded only modest clinical benefit, because of unrecognized complexities in their molecular pathogenesis.12,13 The survival duration of lSM was not significantly different from the normal population.14 On the other hand, treatment and outcome for SM-AHMND is dependent on hematological non-mast cell lineage disease. The clinical course and prognosis are strongly correlated with hematological non-mast cell lineage, and the standard regimen for this non-mast cell disease should be administration together with SM management.4 An earlier study reported the overall median survival rate for patients with SM-AHMND was 24 months, but this survival time varied by subgroup. For example, SM-myeloproliferative neoplasm patients had a significant longer survival time (31 months) than those with SM-chronic myelomonocytic leukemia (15 months), those with SM-myelodysplastic syndrome (13 months), and those with SM-acute leukemia (11 months).15,16 Lim et al identified weight loss, advanced age, thrombocytopenia, anemia, hypoalbuminemia, and excess BM blast as adverse prognostic factors for SM.3 Schipper et al reported a 74-year-old male patient with SM coexisting with DLBCL, and the survival time of this patient was merely seven months owing to lymphoma progression despite immune-chemotherapy administration.17 ln our case, the patient

Table 1

Criteria for systemic mastocytosis diagnosis by World Health Organization.3 Major

Multifocal, dense aggregates of mast cells (15 or more) detected in sections of bone marrow and confirmed by tryptase immunohistochemistry or other special stains Minor

1. In biopsy section, more than 25% of the masts cells in the infiltrate have atypical morphology, or, of all the mast cells in the aspirate smear, more than 25% are immature or atypical

2. Mast cells co-express CD117 with CD2 and/or CD25

3. Detection of KlT point mutation at codon 816 in bone marrow, blood, or other extra-cutaneous organs

4. Serum total tryptase persistently > 20 ng/ml (not a valid criteria in cases of systemic mastocytosis with associated clonal hematologic non-mast cell lineage disease) a Diagnosis may be rendered if one major plus one minor or three minor criteria are fulfilled.

S.-H. Chien et al. / Journal of Cancer Research and Practice xxx (2016) 1—4

responded well to standard regimen for lymphoma and thereafter experienced long-term survival time.

In conclusion, mastocytosis refers to a group of disorders characterized by excessive mast cell accumulation in one or multiple organs, while SM-AHMND is a distinct form of SM characterized by concurrent evolution of two separate clonal entities. BM examination is essential for initial approach which allows for the possibility of detecting both hematological non-mast cell as well as lymphoma staging. Proper course of treatment is guided by the standard regimen for hematological non-mast cell disease. Careful and comprehensive work-up for tumor study or staging is usually the key to disclose coexistent rare disease, and detailed and precise diagnosis may improve patient's outcome.

Conflict of interest

The authors declare no competing interests. References

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