Endocrine DOI 10.1007/s12020-014-0253-7
ENDOCRINE IMAGING
Systemic mastocytosis mimicking carcinoid syndrome D. Iacovazzo • F. Lugli • S. Piacentini • A. Bianchi • F. Inzani • L. M. Larocca • L. Pagano • L. De Marinis
Received: 4 February 2014 / Accepted: 25 March 2014 Ó Springer Science+Business Media New York 2014
Introduction We report the case of a 70-year-old woman who came to our attention in January 2013 complaining of recurrent episodes of severe flushing, diarrhea, dyspnea, and hypotension, that had started in 2011 and were considerably worsening over time, and were partially responsive to steroid and antihistamine drugs. In 2012, suspecting carcinoid syndrome, the patient underwent dosing of chromogranin A (56 ng/ml, n.v.\90), urinary 5-HIAA (6 mg/24 h, n.v. 2–6), and urinary serotonin ? 5-OH tryptophan, which came mildly elevated (11 mg/24 h, n.v. 0–5). A CT scan did not show any liver lesions or other malignancies, and an Octreoscan scintigraphy was negative as well. Nonetheless, the patient was put on octreotide LAR treatment and, in the following weeks, she presented a slight symptomatic improvement. In January 2013, however, the frequency of these crises increased, and the patient was hospitalized at our Institution. Considering the recurring crises and suspecting carcinoid syndrome, short-acting octreotide treatment was
D. Iacovazzo (&) F. Lugli S. Piacentini A. Bianchi L. De Marinis Endocrinology, Catholic University, Policlinico ‘‘A. Gemelli’’, Largo A. Gemelli, 8, 00168 Rome, Italy e-mail: [email protected] F. Inzani L. M. Larocca Anatomic Pathology, Catholic University, Policlinico ‘‘A. Gemelli’’, Rome, Italy L. Pagano Hematology, Catholic University, Policlinico ‘‘A. Gemelli’’, Rome, Italy
started with some improvement. Chromogranin A came normal (33.5 ng/ml, n.v. 19.4–98.1) and urinary 5-HIAA was mildly elevated (19.2 mg/24 h, n.v. 1–10). A new CT scan did not show focal lesions, and a 68Ga-DOTANOC PET-CT did not reveal any pathologic hyperuptake of the tracer. Suspecting systemic mastocytosis, we measured serum tryptase, a serine proteinase contained in mast cells: the levels were markedly elevated (200 mcg/l, n.v. \9.4). Her blood count was unremarkable, and no skin involvement was seen. Bone marrow biopsy was done, and it confirmed the diagnosis of systemic mastocytosis (Fig. 1). Moreover, the KIT D816V mutation was revealed in the bone marrow aspirate. Somatostatin analogue treatment was withdrawn and treatment with dasatinib, a second generation tyrosine kinase inhibitor, was started at the dosage of 100 mg/day. After more than 12 months of treatment, the patient is doing well, without any crises relapse. According to the WHO 2008 classification, major criterion for the diagnosis of systemic mastocytosis is the presence of multifocal dense mast cell (MC) infiltrates in the bone marrow or in another extracutaneous organ; minor criteria are (1) [25 % spindle-shaped cells in MC-infiltrates or [25 % of all MC being atypical MC in bone marrow smears, (2) expression of CD2 and/or CD25 in bone marrow MC, (3) serum tryptase level [20 ng/ml, and (4) KIT point mutation at codon 816 (mostly D816V) in bone marrow or in another extracutaneous organ. The diagnosis can be established if at least 1 major and 1 minor or 3 minor criteria are fulfilled. Indeed our patient presented 1 major and 2 minor criteria for the diagnosis of systemic mastocytosis. We report a case of systemic mastocytosis mimicking carcinoid syndrome. The clinical and biochemical features of these conditions can be highly overlapping [1] and
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Endocrine
somatostatin analogue treatment seems to provide some improvement in these patients. However, negative imaging, bone marrow biopsy, and raised levels of serum tryptase can facilitate the differential diagnosis.
Declaration of interest and funding The authors have nothing to disclose and did not receive any grant supporting the writing of this paper.
Reference 1. L. Izikson, J.C. English, M.J. Zirwas, The flushing patient: differential diagnosis, workup, and treatment. J. Am. Acad. Dermatol. 55, 193–208 (2006) Fig. 1 Bone marrow biopsy showing paratrabecular fibrotic areas with spindled mast cells (arrow) and eosinophils suggestive for systemic mastocytosis (H.E. 940)
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ENDOCRINE IMAGING
Systemic mastocytosis mimicking carcinoid syndrome D. Iacovazzo • F. Lugli • S. Piacentini • A. Bianchi • F. Inzani • L. M. Larocca • L. Pagano • L. De Marinis
Received: 4 February 2014 / Accepted: 25 March 2014 Ó Springer Science+Business Media New York 2014
Introduction We report the case of a 70-year-old woman who came to our attention in January 2013 complaining of recurrent episodes of severe flushing, diarrhea, dyspnea, and hypotension, that had started in 2011 and were considerably worsening over time, and were partially responsive to steroid and antihistamine drugs. In 2012, suspecting carcinoid syndrome, the patient underwent dosing of chromogranin A (56 ng/ml, n.v.\90), urinary 5-HIAA (6 mg/24 h, n.v. 2–6), and urinary serotonin ? 5-OH tryptophan, which came mildly elevated (11 mg/24 h, n.v. 0–5). A CT scan did not show any liver lesions or other malignancies, and an Octreoscan scintigraphy was negative as well. Nonetheless, the patient was put on octreotide LAR treatment and, in the following weeks, she presented a slight symptomatic improvement. In January 2013, however, the frequency of these crises increased, and the patient was hospitalized at our Institution. Considering the recurring crises and suspecting carcinoid syndrome, short-acting octreotide treatment was
D. Iacovazzo (&) F. Lugli S. Piacentini A. Bianchi L. De Marinis Endocrinology, Catholic University, Policlinico ‘‘A. Gemelli’’, Largo A. Gemelli, 8, 00168 Rome, Italy e-mail: [email protected] F. Inzani L. M. Larocca Anatomic Pathology, Catholic University, Policlinico ‘‘A. Gemelli’’, Rome, Italy L. Pagano Hematology, Catholic University, Policlinico ‘‘A. Gemelli’’, Rome, Italy
started with some improvement. Chromogranin A came normal (33.5 ng/ml, n.v. 19.4–98.1) and urinary 5-HIAA was mildly elevated (19.2 mg/24 h, n.v. 1–10). A new CT scan did not show focal lesions, and a 68Ga-DOTANOC PET-CT did not reveal any pathologic hyperuptake of the tracer. Suspecting systemic mastocytosis, we measured serum tryptase, a serine proteinase contained in mast cells: the levels were markedly elevated (200 mcg/l, n.v. \9.4). Her blood count was unremarkable, and no skin involvement was seen. Bone marrow biopsy was done, and it confirmed the diagnosis of systemic mastocytosis (Fig. 1). Moreover, the KIT D816V mutation was revealed in the bone marrow aspirate. Somatostatin analogue treatment was withdrawn and treatment with dasatinib, a second generation tyrosine kinase inhibitor, was started at the dosage of 100 mg/day. After more than 12 months of treatment, the patient is doing well, without any crises relapse. According to the WHO 2008 classification, major criterion for the diagnosis of systemic mastocytosis is the presence of multifocal dense mast cell (MC) infiltrates in the bone marrow or in another extracutaneous organ; minor criteria are (1) [25 % spindle-shaped cells in MC-infiltrates or [25 % of all MC being atypical MC in bone marrow smears, (2) expression of CD2 and/or CD25 in bone marrow MC, (3) serum tryptase level [20 ng/ml, and (4) KIT point mutation at codon 816 (mostly D816V) in bone marrow or in another extracutaneous organ. The diagnosis can be established if at least 1 major and 1 minor or 3 minor criteria are fulfilled. Indeed our patient presented 1 major and 2 minor criteria for the diagnosis of systemic mastocytosis. We report a case of systemic mastocytosis mimicking carcinoid syndrome. The clinical and biochemical features of these conditions can be highly overlapping [1] and
123
Endocrine
somatostatin analogue treatment seems to provide some improvement in these patients. However, negative imaging, bone marrow biopsy, and raised levels of serum tryptase can facilitate the differential diagnosis.
Declaration of interest and funding The authors have nothing to disclose and did not receive any grant supporting the writing of this paper.
Reference 1. L. Izikson, J.C. English, M.J. Zirwas, The flushing patient: differential diagnosis, workup, and treatment. J. Am. Acad. Dermatol. 55, 193–208 (2006) Fig. 1 Bone marrow biopsy showing paratrabecular fibrotic areas with spindled mast cells (arrow) and eosinophils suggestive for systemic mastocytosis (H.E. 940)
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