Mast cells in cutaneous mastocytosis (Toluidine blue stain)
Histopathology: (Toluidine blue stain)
- Low power images highlight the dense band like infiltrate of mast cells in papillary and reticular dermis.
- Perivascular mast cells aggregates are seen.
- Subcutaneous tissues and deep dermal adnexal structures are spared.
- High power images show ovoid epithelioid mast cells with abundant basophilic-purplish granular cytoplasm, due to the presence of metachromatic granules.
- Spindle cell morphology is not seen.
Practical points of Pathoclinics:
- Mast cell disease is very rare. It is a neoplastic mast cell proliferation involving one or more organs. Two categories of mast cell disease are CUTANEOUS MASTOCYTOSIS (most common, 80% of mast cell disease cases) and SYSTEMIC MASTOCYTOSIS (less common, only 20% of cases).
- CUTANEOUS MASTOCYTOSIS (Diagnostic criteria: Mast cell infiltrates confined to the skin, in the absence of systemic involvement) includes urticaria pigmentosa/maculopapular cutaneous mastocytosis (most common of all cutaneous mast cell disease), telangiectasia macularis eruptiva perstans (TMEP), diffuse cutaneous mastocytosis and mastocytoma of skin.
- SYSTEMIC MASTOCYTOSIS includes indolent systemic mastocytosis (most common of all systemic mastocytosis), smoldering systemic mastocytosis, systemic mastocytosis with associated clonal hematological non-mast cell lineage disease, aggressive systemic mastocytosis, mast cell leukemia (MCL), mast cell sarcoma (MCS) and extracutaneous mastocytoma. Bone marrow is almost always involved. Spleen, lymph nodes, liver, and gastrointestinal tract mucosa can be involved in systemic cases. Blood involvement is very rare.
- Diagnostic criteria for systemic mastocytosis: Major criterion + 1 minor criterion /or/ at least 3 minor criteria should be present. Major criterion: Multifocal aggregates of mast cells (≥ 15 mast cells in aggregates) in bone marrow &/or other extracutaneous organs. Minor criteria: 1. > 25% atypical/spindle mast cells in biopsy of bone marrow or extracutaneous organs; 2. Activating point mutation at codon 816 of KIT; 3. Express CD2 &/or CD25 in addition to normal mast cell markers; 4. Serum total tryptase persistently exceeds 20 ng/mL (not valid in cases with associated clonal myeloid disorder).
- Mast cell disease commonly occurs in the pediatric age group, especially in infants and children up to 2 years of age. Cutaneous mast cell disease is much more common in children than in adults. Systemic mast cell disease is generally seen in young and middle-aged adults. Common clinical presentations are skin flushing, blistering and pruritus, headache, acid reflux disease, peptic ulcer disease, diarrhea, shortness of breath, asthma exacerbations, tachycardia, hypotension, syncope, or rarely, even shock in systemic manifestations.
- Important issue in routine histopathology is to distinguish the neoplastic mast cells from reactive normal mast cells. Normal mast cells in tissue sections appear loosely scattered mast cells (not form any aggregates or diffuse or sheets pattern), but may appear as a diffuse interstitial pattern. Morphologically polygonal cells with round to oval nuclei, low nuclear: cytoplasmic ratio, clumped chromatin, inconspicuous nucleoli and abundant dense eosinophilic cytoplasm with basophilic granules. Reactive mast cells have no atypical cytology. Normal mast cells express tryptase, chymase, CD9, CD33, CD45, CD68, and CD117 (KIT), while negative for myelomonocytic markers myeloperoxidase (MPO), CD14, CD15, and CD16 and most T and B cell markers. Mast cells are positive for naphthol-ASD-chloroacetate esterase (CAE). CD2 and CD25 are negative in the majority of reactive mast cells. A reactive population of mast cells are seen in any toxic or chronic inflammatory condition, cutaneous lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia, potent myeloablative chemotherapy.
- Neoplastic mast cells in tissue sections commonly forms multifocal compact aggregates, diffuse sheets, band like infiltrate or diffuse interstitial infiltration or mix pattern. Perivascular collections of mast cells seen in telangiectasia macularis eruptiva perstans (TMEP). Spindle shape with hypogranularity is common in neoplastic mast cells. Frequent bi- or multilobated nuclei are suggestive of aggressive and high-grade disease. Multifocal compact aggregates of mast cells in bone marrow appears as a para-trabecular, perivascular, parafollicular location. Mast cells are intermingled with lymphocytes, eosinophils, histiocytes, and fibroblasts. Bone marrow may show diffuse reticulin fibrosis and thickening of bony trabeculae. Metachromatic blast cells are seen in mast cell leukemia. Mitotic figures are not common even in aggressive or leukemic variants. Neoplastic mast cells have a similar antigen profile to normal mast cells; however, neoplastic cells co-express CD2 &/or CD25. Here the cell of interest should not be mistaken as CD2 positive T cells. Also, CD25 expression may be negative or weak in well-differentiated mast cell disease. CD117 strongly highlights the increased numbers of perivascular spindle-shaped mast cells in TMEP.
- The most common mutation is D816V in exon 17 within KIT protooncogene. Rare familial cases with germline mutations of KIT have been reported. About 1/3 of systemic mastocytosis cases are associated with TET2 mutations.
- The majority of pediatric cases have improvement of symptoms over time (complete regression by adolescence seen in > 50% of cases) and in general no specific treatment required except antihistamines, mast cell degranulators and topical steroids. Transformation to systemic mastocytosis is more likely in diffuse cutaneous mastocytosis than urticaria pigmentosa. In adults, cutaneous lesions generally do not regress and are often associated with systemic mastocytosis. Usually, adults have normal life expectancy, but some have aggressive course with survival of a few months. No curative therapy for systemic mast cell disease, however, PKC412 tyrosine kinase inhibitor may be effective in treating systemic mastocytosis with mutated KIT.
- Percentage of mast cells along with abnormal morphology in bone marrow is an independent predictor of survival in systemic mastocytosis.