Mast cell tumor differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2] Zahir Ali Shaikh, MD[3] Suveenkrishna Pothuru, M.B,B.S. [4]

Overview

Mast cell tumor must be differentiated from other diseases that cause flushing,such as: phaeochromocytoma and carcinoid syndrome.[1] Mast cell tumor must be differentiated from other diseases that cause elevated serum tryptase levels and cytopenia, such as: myelodysplastic syndrome, primary myelofibrosis, essential thrombocythemia, and chronic eosinophilic leukemia.

Differential Diagnosis

Mast cell tumor must be differentiated from other diseases that cause flushing:[1]

Mast cell tumor must be differentiated from other diseases that cause abdominal pain and discomfort:

Mast cell tumor must be differentiated from other diseases that cause elevated serum tryptase levels and cytopenia, such as:

Differentiating Myeloproliferative Disorders

ABBREVIATIONS

N/A: Not available, NL: Normal, FISH: Fluorescence in situ hybridization, PCR: Polymerase chain reaction, LDH: Lactate dehydrogenase, PUD: Peptic ulcer disease, EPO: Erythropoietin, LFTs: Liver function tests, RFTs: Renal function tests, LAP: Leukocyte alkaline phosphatase, LAD: Leukocyte alkaline dehydrgenase, WBCs: White blood cells.

Myeloproliferative neoplasms (MPN) Clinical manifestations Diagnosis Other features
Symptoms Physical examination CBC & Peripheral smear Bone marrow biopsy Other investigations
WBCs Hb Plat-
elets
Leuko-cytes Blasts Left
shift
Baso-
phils
Eosino-
phils
Mono-
cytes
Others
Chronic myeloid leukemia
(CML), BCR-ABL1+[2][3]
<2% + N/A NL
Chronic neutrophilic leukemia (CNL)[4][5][6] Minimal + NL NL NL
Polycythemia vera
(PV)[7][8][9][10]
  • Constitutional
NL or ↑ None - ↑ or ↓ NL or ↑ NL ↑↑ NL
  • Hypercellularity for age with tri-lineage growth
Primary myelofibrosis (PMF)[11][12][13][14] Erythroblasts - Absent NL NL
  • Variable with fibrosis or hypercellularity
Essential thrombocythemia (ET)[15][16][17]

NL or ↑

None

-

↓ or absent

NL

NL

  • N/A

↑↑

  • Normal/Hypercellular
Chronic eosinophilic leukemia,
not otherwise specified
(NOS)[18][19][20][21]
Present + ↑↑
MPN,
unclassifiable
Variable ± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • N/A
Mastocytosis[22][23][24][25]
  • Constitutional
None - NL NL ↓ or ↑
Myeloid/lymphoid neoplasms
with eosinophilia and rearrangement
of PDGFRA, PDGFRB, or FGFR1,
or with PCM1-JAK2[26][27][28][29]
NL - NL
  • None
NL
  • FISH shows t(8;13) and t(8;22)
B-lymphoblastic leukemia/lymphoma[30][31] NL or ↑ >25% N/A ↑ or ↓ ↑ or ↓ ↑ or ↓
Myelodysplastic syndromes
(MDS)[32][33]
Variable -
  • Leukemia transformation
  • Acquired pseudo-Pelger-Huët anomaly
Acute myeloid leukemia (AML)
and related neoplasms[34][35]
NL or ↑ N/A ↑ or ↓ ↑ or ↓ ↑ or ↓

with dysplasia

Blastic plasmacytoid
dendritic cell neoplasm
[36][37][38][39]
NL NL NL NL
Myelodysplastic
/myeloproliferative
neoplasms
(MDS/MPN)
Chronic myelomonocytic leukemia (CMML)[40]
[41][42]
< 20% NL ↑↑
  • Overlapping of both, MDS and MPN
  • Absolute monocytosis > 1 × 109/L (defining feature)
  • MD-CMML:WBC ≤ 13 × 109/L (FAB)
  •  MP-CMML:WBC > 13 × 109/L (FAB)
Atypical chronic myeloid leukemia (aCML), BCR-ABL1-[43][44] <20% + <2% of WBCs N/A N/A
  • N/A
Juvenile myelomonocytic leukemia (JMML)[45][46] N/A N/A N/A
MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)[47][48][49]
  • Variable
NL or ↑ NL - NL N/A N/A
T-lymphoblastic leukemia/
lymphoma
T-lymphoblastic leukemia/
lymphoma
[50][51][52]
>25% blasts (Leukemia)

<25% blasts (Lymphoma)

± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • LDH
  • Positive for TdT
  • Hypercelluarity with increased T cells precursors
Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymph[53] ± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • N/A
Provisional entity: Early T-cell precursor lymphoblastic leukemia[54][55] ± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • Hypercelluarity with increased T cells precursors

Differentiating mast cell tumor from other causes of abdominal pain and diarrhea

Mast cell tumor must be differentiated from other causes of abdominal pain and diarrhea.

Diseases Clinical manifestations Para-clinical findings Gold standard Additional findings
Symptoms Physical examination
Lab Findings Imaging Histopathology
Abdominal pain Diarrhea Flushing Dyspnea Palpitations Other symptoms Wheezing Telangiectasia Hypotension Tachycardia Systolic murmur of tricuspid regurgitation Other physical findings Urinary 5-hydroxyindoleacetic acid (5-HIAA) Serum Chromogranin A (CgA) Other markers Abdominal computed tomography (CT) Abdominal MRI Somatostatin receptor scintigraphy [SRS], or Octreoscan Metaiodobenzylguanidine (MIBG) scintigraphy Other diagnostic studies Transthoracic echocardiography
Carcinoid Syndrome[56][57][58][59][60][61][62][63][64] Neuroendocrine tumor of midgut [65][66][67][68] +

Mild

+ + + +

Dermatitis

Diarrhea

Dementia

Metastatic tumors in the liver: Right upper quadrant pain, hepatomegaly, and early satiety

+ +/- +/- + + - + + + +
  • Valve thickening with retraction and reduction in the mobility of the tricuspid valve

Pathognomonic radiological sign of midgut NET.

Neuroendocrine tumor of lung[69][70][71][72] + + + + +
+ +/- +/- + + - + + Sensitive for detection of liver metastases if present + + - Typical low-grade:bland cells containing regular round nuclei with finely dispersed chromatin and inconspicuous small nucleoli.Mitotic figures are scarce and necrosis is absent.

Intermediate-grade atypical: presence of Neuroendocrine morphology and either necrosis or 2 to 10 mitoses per 10 HPF

Irritable Bowel Syndrome[73][74][75][76] +

Perioidic

- - - - - - - - - - - - - - - - Rome IV criteria
  • Recurrent abdominal pain, at least 1day/week in the last 3 months, a/s with 2 or more of the following criteria:

•Related to defecation

•Associated with a change in stool frequency

•Associated with a change in stool form (appearance)

Malignant neoplasms of small intestine[77][78][79] +/- +/- - - +/- - - +/- - * Abdominal mass - + Abdominal CT scan may be diagnostic of small intestine cancer. Findings on CT scan suggestive of small intestine cancer include intrinsic mass with a short segment of bowel wall thickening MRI and MRI enteroscopy are other advance modalities to diagnose and stage small intestinal cancers - - Enteroscopy, capsule endoscopy and double balloon enteroscopy Biopsy and histopathology
Crohn disease[80][81][82][83] +/- - - - - - - - - - - - - -
  • Focal ulcerations and acute and chronic inflammation
Benign cutaneous flushing[84] - - + - - - - - - - - - - - - - - - - - - -
Systemic mastocytosis[85][86][87][88][89] + + + + - +/- +/- + - - - - - -
Asthma exacerbation[90][91][92][93] - - - + + + - - + -
  • Tachypnea
  • Prolonged expiratory phase of respiration (decreased I:E ratio)
  • Seated position with use of extended arms to support the upper chest (tripod position)
  • +/- Pulsus paradoxus
- - - -- - - - Chest X ray -
  • Loss of the normal pseudostratified structure of airway epithelium
  • Increase in the proportion of goblet cells
  • Fibrotic thickening of the sub-epithelial reticular basement membrane
  • Increased numbers of myofibroblasts
  • Increased vascularity
  • Increased airway smooth muscle mass
  • Increased extracellular matrix
Anaphylaxis[94][95][96][97][98] + -/+ + + + +/- - + + - - - - - - - - - - History of exposure to insect stings,food alllergy,rubber latex,food additives,,allergy to medications,physical factors such s excercise and cold
Histaminergic Angioedema[99][100][101][102][103] +/- +/- + + + + - + + - - - - - - - - - -
  • Take proper clinical history of previous similar episodes
  • Medication history
  • Any allergy to insects stings , foods or any ingestion within previous 24 hours
Medullary Thyroid Carcinoma[104][105][106][107] - +/- +/- +/- - - - - - - - - - - - -

For metastasis

-

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