Mast Cell Sarcoma in an Infant: a Case Report and Review of the Literature
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CLINICAL AND LABORATORY OBSERVATIONS Mast Cell Sarcoma in an Infant: A Case Report and Review of the Literature Marnelli A. Bautista-Quach, MD,* Cassie L. Booth, MD,* Albert Kheradpour, MD,w Craig W. Zuppan, MD,* Edward H. Rowsell, MD, PhD,* Lawrence Weiss, MD,z and Jun Wang, MD* CASE REPORT Summary: Mast cell diseases comprise a spectrum of disorders This male infant first presented with foul-smelling, purulent including cutaneous mastocytosis, indolent or aggressive systemic otorrhea of the right ear beginning at about 4 months of age. He variants including leukemia, and unifocal tumor formations such was treated with antibiotics and ear drops for otitis and the otor- as benign extracutaneous mastocytoma or aggressive mast cell rhea resolved, but he continued to behave as if the ear irritated him. sarcoma (MCS). Many mast cell diseases are associated with Imaging performed at that time, from an outside institution, aberrancy of c-KIT proto-oncogene resulting in tyrosine kinase showed a 5-mm soft tissue mass involving the right distal auditory activity, typically exhibiting point mutation in codon 816. MCS is canal adjacent to the tympanic membrane. No evidence of soft an exceedingly rare clinicopathologic entity characterized by a tissue invasion or bone erosion was seen. Follow-up physical unifocal accumulation of neoplastic mast cells that grow in a examination at 8 months of age showed a large, polypoid, soft locally destructive manner. We report a case in a 2-year-old boy tissue mass causing near complete obstruction of the right external who was initially diagnosed at 8 months of age with atypical auditory canal. A biopsy of this mass revealed a subcutaneous cutaneous mastocytoma of the right ear with subsequent aggres- infiltrate of mildly atypical monocytic-like or histiocytic-like cells sive, destructive growth pattern; features that were most consistent with folded or polylobated nuclei admixed with significant numbers with MCS. So far, MCS has been documented in the literature in at of eosinophils (Figs. 1A, B). No Touton-type giant cells were least 6 human cases. To the best of our knowledge, our case rep- identified. At that time, this was interpreted as an “atypical” CM resents the first MCS in an infant. Thorough multimodal approach based on the clinically localized growth without definite evidence of with strict follow-up is relevant in appropriately diagnosing this destructive growth pattern as per outside imaging impression, rare entity, particularly in differentiating this lesion from other positive staining for tryptase (Fig. 1C), CD68, and CD117 neoplasms that are more likely to occur in infancy. (Fig. 1D), and expression of CD43. Of additional concern was the lack of classic metachromatic granules on Giemsa stain. Immu- Key Words: mast cell sarcoma, mastocytosis, temporal bone nohistochemical (IHC) stains for CD2 and CD25 from the initial (J Pediatr Hematol Oncol 2013;35:315–320) biopsy were both negative. Langerhans cell histiocytosis (LCH), granulocytic sarcoma, and histiocytic sarcoma were considered, but were excluded or considered highly unlikely based on negative staining for CD1a protein (Fig. 1E), S100 (Fig. 1F), myeloperox- ast cell disease (MCD) is a group of lesions that idase (MPO), CD34, CD45, and CD163, respectively. Mencompasses cutaneous mastocytosis (CM), systemic At the age of 11 months, 3 months after initial diagnosis, fol- variants, and unifocal tumor formation including extrac- low-up imaging (Fig. 2) revealed rapid disease progression manifested utaneous mastocytoma and mast cell sarcoma (MCS).1,2 by a destructive, 3.3Â3.8Â3.6 cm, lesion arising from the right pet- MCS is an extremely rare entity with only 6 documented rous temporal bone and extending through the skull base, involving human cases in the literature.3–8 We report a case in a now the carotid sheath, and effacing or occluding the right jugular vein. The initial mass had been biopsied but not resected, and no treatment 2-year-old boy who, at 8 months of age, was found to have had been given during this interval. Serum tryptase level was elevated a unifocal right ear mass that was initially diagnosed as at 34.1 ng/mL (reference range, <11.5 ng/mL). atypical CM, and subsequently was demonstrated to Subsequent biopsies showed a lesion histologically identical to actually be MCS due to the aggressive and destructive the initial biopsy with the exception of a small, previously unsampled tumor growth pattern. This represents the first case of MCS population of cells (2% to 5%) showing mild to moderate atypia documented in an infant. (Fig. 3A). The tumor cells had a low Ki-67 proliferation index (1% to 2% overall; Fig. 3B) and were positive for CD33, CD68, CD117, and focally reactive for CD25. IHC stains for CD2, CD34, CD45, and S100 were again negative. Flow cytometry analysis of the tumor (Fig. 4) showed a population of cells (B40% of total events) Received for publication December 16, 2011; accepted July 25, 2012. expressing myeloid markers CD11b (Fig. 4B), CD13 (Fig. 4C), and in From the Departments of *Pathology and Laboratory Medicine; particular, CD9, CD33 (Fig. 4D), and CD117 (Fig. 4E), but not w Pediatric Hematology and Oncology, Loma Linda University expressing CD15 (Fig. 4C), CD36 (Fig. 4B), CD56 (Fig. 4F), and z Medical Center, Loma Linda, CA; and Clarient Inc., Aliso Viejo, CD25 (Fig. 4E), similar to the CD25 IHC result from the initial CA. M.B.Q., C.L.B., A.K., C.W.Z., E.H.R., L.W., and J.W.: participated in biopsy but was in contrast to the focal CD25 reactivity noted on the the composition of this case report. M.B.Q., C.L.B., C.W.Z., concurrent IHC analysis. This discrepancy was likely secondary to E.H.R., L.W., and J.W.: interpreted the morphologic, special stains sampling variation. Flow cytometry for CD2 yielded an equivocal and IHC findings, performed literature search and review, and result (Fig. 4). A stain for langerin was negative. Electron microscopy procured photomicrographs. C.W.Z.: interpreted the EM findings. showed nonspecific cytoplasmic features, with neither typical mast E.H.R.: interpreted the flow cytometry data and provided the scat- cell nor Birbeck granules. Chromosomal studies of the tumor cells tergrams. A.K.: presented additional relevant clinical information. showed a normal 46, XY karyotype. Polymerase chain reaction The authors declare no conflict of interest. analysis on fresh tumor tissue was performed at Stanford University Reprints: Jun Wang, MD, Department of Pathology and Laboratory Medicine, Room 2516, 11234 Anderson Street, Loma Linda, CA Medical Center (Palo Alto, CA). This polymerase chain reaction test 92354 (e-mail: [email protected]). included specific evaluation of c-KIT exons 8 and 17, and no muta- Copyright r 2012 by Lippincott Williams & Wilkins tions were detected. J Pediatr Hematol Oncol Volume 35, Number 4, May 2013 www.jpho-online.com | 315 Bautista-Quach et al J Pediatr Hematol Oncol Volume 35, Number 4, May 2013 FIGURE 2. Magnetic resonance imaging of the head showing a destructive 3.3Â3.8 cm lesion arising from the right petrous temporal bone and extending through the skull base (sagittal view). FIGURE 1. A and B, Hematoxylin and eosin stain of the initial biopsy of the auditory canal mass showing a subcutaneous infil- trate of monocytoid or histiocytoid cells with folded or poly- lobated nuclei admixed with significant numbers of eosinophils (A: Â100, B: Â400). Immunohistochemistry showing expression of tryptase (C, Â200) and CD117 (D, Â400). CD1a (E, Â400) FIGURE 3. A, Hematoxylin and eosin stain of the second biopsy and S100 (F, Â400) were negative, essentially ruling out Lan- of the destructive mass showing mild to moderate nuclear atypia gerhans cell histiocytosis. (Â400). B, The neoplastic cells demonstrate a low proliferation index, with Ki-67 nuclear positivity in only about 1% to 2% of tumor cells (Â200). 316 | www.jpho-online.com r 2012 Lippincott Williams & Wilkins J Pediatr Hematol Oncol Volume 35, Number 4, May 2013 Mast Cell Sarcoma in an Infant FIGURE 4. Gating is applied on the granulocyte region as depicted on the flow cytometry scattergram of side scatter versus CD45 (A). A population of cells (B40% of the total events) expresses CD11b and CD13 (B and C, respectively), CD9, CD33 and CD117 (D and E, respectively), but the population of interest do not express CD15, CD36, CD25, and 56 (C, B, E, and F, respectively). CD2 expression was equivocal (F). Despite a milder degree of cellular atypia than described in cell lineage disease, aggressive systemic mastocytosis, and previous cases,3–8 and the absence of the most common c-KIT mast cell leukemia (MCL) are more commonly observed in mutations in MCD, the clinical, radiologic, histologic, and immu- adults. Other variants consist of a unifocal infiltrate of nophenotypic characteristics were most consistent with MCS. neoplastic mast cells without evidence of systemic involve- Complete staging work-up showed no evidence of bone marrow or ment. Examples of the latter include MCS and extracuta- peripheral blood involvement. He underwent tumor debulking surgery followed by a month-long trial of imatinib (150 mg/d) with neous mastocytoma (ECM), with the former characterized no clinical or radiographic evidence of tumor response. He was by a destructive pattern of growth, typically showing high- subsequently placed on an investigational oral regimen, protein grade cytomorphology, whereas ECM demonstrates a kinase C-412 (PKC412; 40 mg, tid) and has recently completed 12 nondestructive growth pattern and low-grade cytology.1,2 months of therapy with no significant adverse effects. Minimal Mutations of c-KIT oncogene in the tyrosine kinase decrease in residual tumor size, evident from subsequent radio- domain, expressing substitution from aspartate to valine at graphic impressions, from 2.1Â2.7 to 2.1Â2.4 cm was noted after codon 816 (D816V) have been detected in most cases of the first 6 months of treatment with the aforementioned agent.