| Abstract|| |
Systemic mastocytosis is a rare clonal disorder characterized by mast cell infiltration of one or more organs, with or without skin involvement. Leonine facies is a rare presentation and corresponds to the morphologic manifestation of diffuse dermal infiltration of the face as a result of long standing disease. Bone marrow aspiration and biopsy findings in a 60-year-old woman, who had extensive cutaneous infiltration due to systemic mastocytosis, resulting in 'leonine facies,' are described, and causes of leonine facies are discussed.
Keywords: Bone marrow aspiration, leonine facies, systemic mastocytosis
|How to cite this article:|
Mutreja D, Purohit A, Singh PK, Pati H P. A 60-year-old lady with leonine facies: A rare diagnosis. Indian J Pathol Microbiol 2012;55:566-8
| Introduction|| |
Mastocytosis is a clonal disease derived from hematopoietic bone marrow progenitor cells that manifests with an unusually broad-spectrum of clinical and morphologic appearances. Systemic mastocytosis is a rare disease characterized by proliferation and accumulation of mast cells within various organs, most commonly the skin. The clinical course is variable; indolent or smoldering, and aggressive forms have been described. , Leonine facies is rare and corresponds to the morphologic manifestation of diffuse dermal infiltration of the face. It can occur in a variety of conditions, although it is more frequent in association with lepromatous leprosy and cutaneous T-cell lymphomas. ,,,, Leonine facies is an atypical presentation of mastocytosis and has been reported in only one earlier report so far. 
| Case Report|| |
A 60-year-old lady presented to the clinic for evaluation of skin-colored nodular eruptions over entire body of 8 years duration. The lesions were initially limited in distribution to trunk and abdomen, which had progressed gradually to involve face and extremities. There was no history of tingling numbness or weakness or associated hair loss. Patient had been treated with anti-histaminics in the past and subsequently had been lost to follow-up. Examination revealed an averagely-built elderly woman with normal vitals. Skin examination showed 80% involvement with symmetrical, discrete to confluent, soft, skin-colored papulo-nodular lesions over extremities and trunk, with slight flexural sparing. Face showed large coalescent papules, nodules, and plaques resulting in leonine appearance [Figure 1]. Darrier's sign was positive. Oral cavity, palms, soles, and scalp were normal. There was no evidence of peripheral nerve thickening.
|Figure 1: Coarse nodular appearance with deep creases on face resulting in characteristic 'leonine facies'|
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Investigations showed raised serum bilirubin and transaminases; (Serum bilirubin: 3.2 mg/dL, AST: 1659 IU/L, ALT: 1729 IU/L, and ALP: 1729 IU/L). Routine hemogram and renal parameters were normal. Slit skin smears stained by the Ziehl-Neelsen technique for acid-fast lepra bacilli were repeatedly negative. Serum tryptase levels were 204 ng/ml and 168 ng/ml on repeated testing 10 days apart (reference range, <11.5 ng/ml). Ultrasound abdomen showed hepatomegaly. A bone scan showed osteopenia. Bone marrow aspirate smears were normocellular and showed clusters of mast cells, each comprising of 10-15 mast cells, with round to spindled morphology and dense cytoplasmic granulation [Figure 2]a and b. Bone marrow biopsy sections showed confluent, dense paratrabecular infiltrates of mast cells (accounting for more than 30% of the section) and interstitial infiltrates in clusters of more than 15 cells [Figure 3]a and b. Mast cells were monomorphic, evenly spaced with abundant clear to pale pink cytoplasm. There were no associated features of myelodysplasia or other hematological malignancy in the smears and sections studied. Skin biopsy sections also showed CD117-positive mast cells infiltrating the dermis. No granulomas or acid-fast bacilli were seen. In view of the findings above and elevated serum tryptase levels, a diagnosis of systemic mastocytosis was confirmed.
|Figure 2: (a) Bone marrow aspirate smear showing clusters of mast cells; inset shows spindled morphology of mast cell (Jenner Giemsa, × 400). (b) Toluidine blue highlighting mast cell clusters in bone marrow aspirate smear with metachromatically staining cytoplasmic granulation; inset shows spindle-shaped mast cell, (Toluidine blue, × 400)|
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|Figure 3: (a) BM biopsy section showing mast cells in sheets with prominent paratrabecular infiltration (H and E, × 100). (b) Mast cells with voluminous clear to pale pink cytoplasm in clusters in bone marrow biopsy section (H and E, × 400)|
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| Discussion|| |
Mastocytosis is a disorder of mast cell proliferation in body tissues. It usually presents in the skin, but may affect other tissues, especially the bone marrow and gastrointestinal tract. Disease involvement may be primarily cutaneous, as seen most commonly in the pediatric population, or systemic, as is more typical of adult-onset disease. 
Leonine facies is rare and corresponds to the morphologic manifestation of diffuse dermal infiltration of the face. Papules fusing together into plaques resulting in grooves and fissures on the face create this appearance.  It has been classically described for lepromatous leprosy. Apart from leprosy, leonine facies has been reported associated with granulomatous lesions like cutaneous sarcoidosis, leishmaniasis, chronic dermatologic disorders, namely actinic reticuloid, scleromyxedema, and hematological malignancies, mainly mycosis fungoides and leukemia cutis. ,,, Most of the time, it occurs as the diseases progress without therapy, like in this case.
The major diagnostic criterion for mastocytosis is focal compact tissue infiltrate predominantly composed of mast cells. The minor diagnostic criteria are as follows: (1) prominent spindling of mast cells (>25%), (2) atypical immunophenotype of mast cells with expression of CD25, (3) activating point mutation of c-kit in codon 816 (usually KITD816V), and (4) chronically elevated serum tryptase level (>20 ng/mL). Diagnosis of mastocytosis can be established if the major and at least 1 minor criterion or at least 3 minor criteria (when the major criterion is not fulfilled) are present. To be able to separate the different forms of systemic mastocytosis, clinical symptoms, especially the so-called B findings, referring to an organomegaly (hepatosplenomegaly and/or lymphadenopathy), and even C findings, indicating organ dysfunction due to widespread mast cell infiltration (e.g., cytopenia and/or ascites in aggressive systemic mastocytosis with strong infiltration of bone marrow and liver) are taken into account.  The presence of multiple large mast-cell aggregates in the bone marrow of this patient constituted a major criterion for the diagnosis of systemic mastocytosis. In addition, an elevated serum tryptase levels fulfilled the diagnostic criteria for systemic mastocytosis. Our patient also had B findings in form of hepatomegaly, and thus can be placed in the diagnostic category of smoldering systemic mastocytosis.
Systemic mastocytosis may be associated with a clonal non-mast-cell hematologic neoplasm (e.g., a myelodysplastic syndrome or chronic myelomonocytic leukemia) or acute myeloid leukemia in 30% to 40% of cases. In these cases, the prognosis is typically determined by that of the associated non-mast-cell neoplasm. Many of these myeloid neoplasms have been shown to share KIT mutation and cytogenetic abnormalities with the mast-cell proliferation, indicating an origin from a common precursor cell.  In this patient, there was no morphologic evidence of an associated hematologic neoplasm.
The management of mastocytosis depends on the clinicopathological subtype. Reduction of the mast-cell burden is indicated in cases of aggressive mastocytosis and mast-cell leukemia, and treatment of the non-mast-cell hematologic disorder is indicated in cases of mastocytosis with such a disorder.  At present, there is no curative treatment of mastocytosis. The patients with indolent mastocytosis typically have a slow progression over time. According to current recommendations, these patients should be monitored closely. Treatment in these patients is aimed at avoiding triggers, limiting release of mediators, and blocking their actions.  Our patient is being managed with H1 and H2 anti-histaminics (cetrizine and ranitidine), cromolyn sodium, and oral cyclophosphamide and is on close follow-up.
In conclusion, with its variable clinical phenotypes, systemic mastocytosis is a great masquerader.  As in this patient, the onset of symptoms can precede the diagnosis by many years.
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Department of Haematology, All India Institute of Medical Sciences, New Delhi
[Figure 1], [Figure 2], [Figure 3]