Multicentric infantile myofibromatosis

International Journal of Pediatric Otorhinolaryngology 45 (1998) 249 – 254

Case report

Multicentric infantile myofibromatosis Philomena Mufalli Behar a,*, Ford D. Albritton a, Susan Muller a,c, N. Wendell Todd a,b a

Department of Otolaryngology-Head and Neck Surgery, Emory Uni6ersity, 1365 Clifton Road, NE Atlanta, GA 30322, USA b Department of Pediatrics, Emory Uni6ersity, 1365 Clifton Road, NE Atlanta, GA 30322, USA c Department of Pathology and Laboratory Medicine, Emory Uni6ersity, 1365 Clifton Road, NE Atlanta, GA 30322, USA Received 18 February 1998; received in revised form 19 July 1998; accepted 24 July 1998

Abstract Infantile myofibromatosis (IM) is a rare tumor of infancy and childhood, typically presenting as a firm, nodular mass involving soft tissue, bone or viscera. Approximately one-third of cases involve the head and neck. These tumors can be solitary or multicentric. Biopsy reveals tumor cells that resemble myofibroblasts. Spontaneous regression may occur. A high degree of suspicion is necessary to differentiate this entity from other more aggressive processes — histiocytosis, fibrosarcoma, rhabdomyosarcoma. We describe the case of a male infant with multicentric myofibromatosis, presenting with multiple thoraco-abdominal subcutaneous nodules and lytic mass lesions of the temporal bone and calvarium. The characteristic clinical, radiologic and histopathologic features of this process are reviewed along with diagnostic and therapeutic options. © 1998 Published by Elsevier Science Ireland Ltd. All rights reserved. Keywords: Myofibromatosis; Congenital; Temporal bone; Multicentric; Skull

1. Introduction Infantile myofibromatosis (IM) is a rare tumor of infancy and childhood, characterized by single or multiple firm, non-tender nodular masses of the skin, soft tissue, bone or viscera [1]. First * Corresponding author. Tel.: + 1 404 7785717; fax: +1 404 7784295.

described as ‘congenital fibrosarcoma’ in 1951 by Williams and Schrum [2], Stout [3] later used the term ‘congenital generalized fibromatosis’. In 1981, Chung and Enzinger [4] reviewed 61 cases and, based on histologic features, gave the disease its current name, infantile myofibromatosis. Three forms of the disease are currently recognized: solitary (most common), multicentric and multicentric with visceral involvement [1]. Approxi-

0165-5876/98/$ - see front matter © 1998 Published by Elsevier Science Ireland Ltd. All rights reserved. PII S0165-5876(98)00105-0

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Fig. 1. Lateral skull X-ray demonstrating the lytic, well circumscribed lesion with sclerotic margins in the parietal region (arrow).

Fig. 2. Non-contrast CT scan of skull (bone window, axial image) demonstrating an expansile mass in the left parietal region (arrow) causing widening of the inner and outer calvarial tables and cortical bone erosion.

P. Mufalli Behar et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 249–254

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Fig. 3. Non-contrast CT scan of temporal bone (bone window, axial image) demonstrating a lytic lesion in the right temporal bone with areas of central calcification (arrow).

Fig. 4. Low power hematoxylin and eosin stain of the parietal skull lesion showing a proliferation of spindle cells arranged in whorls and fascicles ( × 100 magnification).

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mately one-third of cases involve the head and neck region and therefore it is of importance to the otolaryngologist [4]. In addition, IM can mimic other conditions, such as histiocytosis X, fibrosarcoma and rhabdomyosarcoma and must be differentiated from these to avoid the morbidity of unnecessary treatment.

2. Case report A full term, male infant with tetralogy of Fallot, presented at birth with multiple subcuta-

neous mass lesions of the chest and abdomen. An additional subcutaneous mass was noted in the left parietal area. The patient’s cardiac disease was the major problem for a few months. At age 6 months, biopsy of an abdominal lesion was consistent with IM. The infant was referred for otolaryngic evaluation at 11 months of age. A firm, subcutaneous, non-mobile 3 cm nodule was palpable in the left parietal region of this otherwise healthy appearing infant. The overlying skin was normal. The head circumference was normal. There were no middle ear effusions. The remainder of the head and neck

Fig. 5. High power hematoxylin and eosin stain of the same lesion demonstrating two predominant cell types: plump spindle shaped cells resembling smooth muscle and polyhedral cells with scant cytoplasm ( ×400 magnification). Table 1 Summary of clinical features of various forms of IM Solitary

Relative frequency Gender predisposition Prognosis Spontaneous regression Etiology

\1/2 M\F Excellent Yes Unknown

Multicentric Without visceral

With visceral involvement

1/3 M =F Good Yes Unknown

B1/6 M =F \75% die as neonate Yes Unknown

P. Mufalli Behar et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 249–254 Table 2 Differential diagnosis of infantile myofibromatosis Radiographic

Histopathologic

Histiocytosis X Dermoid Epidermoid Osteoblastoma Hemangioma Lymphangioma Neurofibroma Fibrosarcoma Metastatic neuroblastoma Fibrous dysplasia

Fibrosarcoma Rhabdomyosarcoma Fibrous histiocytoma Peripheral nerve sheath tumor Myxoma

examination was normal. Multiple similar nodules were present in the subcutaneous tissue of the abdomen and chest. Developmental milestones were appropriate for age. The remainder of the physical examination was unremarkable. A lateral skull radiograph revealed a well circumscribed, lytic lesion with a sclerosing margin, in the parietal area at the junction of the squamosal and coronal sutures (Fig. 1). A noncontrast, computed tomography (CT) scan showed an erosive, hypodense lesion of the left parietal area and an additional similar lesion involving the right temporal bone, anterior to the middle ear. The parietal lesion caused widening of the inner and outer calvarial tables; the temporal bone lesion contained central calcifications (Figs. 2 and 3). At 11 months of age, the patient was taken to the operating room where excisional biopsy of the left parietal lesion was performed. It was enucleated without difficulty and was firm, white and rubbery in appearance. The lesion extended to the dura without invasion. Histologic examination of the abdominal and parietal lesions were identical and demonstrated spindle cells resembling myofibroblasts (Figs. 4 and 5). Immunohistochemical staining was positive for smooth muscle actin and vimentin and negative for desmin. This supports the diagnosis of IM. The temporal bone lesion was not biopsied, but remains asymptomatic. Serial ear examinations remain unremarkable. At age 16 months, the patient is doing well with no evidence of recurrence at the sites of previous excision.

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3. Discussion Although IM is the most common fibrous proliferation of infancy, it is a little known entity. A high index of suspicion is required to make the diagnosis. The solitary form accounts for more than half of cases [1,4]. It is twice as common as the multicentric varieties and is more prevalent in males. The multicentric varieties show no gender predisposition. Patients with multicentric disease with visceral involvement have a worse prognosis, with 75% of patients dying in the neonatal period [1,4–7] (Table 1). The etiology of this disorder is unknown. Intra-uterine estrogen exposure has been proposed as a possible contributing factor. Both autosomal dominant and recessive modes of inheritance have been postulated [7,8]. Clinically, the tumor presents as single or multiple painless, slow growing mass lesions occurring in the dermis, subcutis, muscle, bone or viscera, ranging in size from millimeters to several centimeters [6]. At birth, 50% of the lesions are present and enlarge during the first few months of life [7]. The rate of spontaneous resolution is unknown, however, in the absence of visceral involvement, spontaneous resolution is expected [4]. Recently, apoptotic cell death has been proposed as a possible mechanism for this regression [9]. Approximately one-third of the lesions present in the head and neck [4]. The majority of lesions occur in cutaneous or skeletal tissues. Calvarial bone involvement is common, although any bone may be affected [1,5,6]. Solitary lesions of the orbit, calvarium and temporal bone have been described [5–7,10,11]. Visceral involvement may occur in the lungs, heart, or gastrointestinal tract and may result in compromise of these organs [1,4]. Rarely, the central nervous system is affected [1,10]. Symptoms are few unless visceral involvement is present. Pain may occur and is related to compression of adjacent neural structures. Large lesions may become ulcerated [1,4]. Visceral involvement occurs in 37% of patients with multicentric disease and may result in death due to acute cardiopulmonary failure, hemorrhage and gastrointestinal obstruction [5].

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The histologic features of IM can be quite variable and therefore the differential diagnosis is broad (Table 2). Short bundles and fascicles of spindle shaped cells with myofibroblastic features characterize the lesion [5]. Round, less differentiated cells organized in a pericytoma-like pattern may also be present [9]. Variations in the microscopic appearance of this tumor occur and hinder the diagnosis. Although not seen in our patient, nuclear atypia, necrosis, or calcifications can be observed [1,4]. As a result, IM is occasionally misdiagnosed as a soft tissue malignancy, such as fibrosarcoma or rhabdomyosarcoma. Immunostaining for vimentin and actin can be helpful in separating IM from these entities. In addition, electron microscopy may be helpful in demonstrating cells with both fibroblastic and myofibroblastic features [10]. The characteristic roentgenographic features of IM involving bone are a well circumscribed, lytic lesion with sclerotic margins [8]. If a calvarial lesion is present, CT may reveal a lytic lesion causing expansion of the inner and outer tables [8,12]. Central areas of calcification may also be present [10]. Magnetic resonance imaging (MRI) has also been proposed for evaluation of the extent of visceral involvement. T1 weighted images reveal a mass with low signal intensity, while T2 weighted images show increased intensity [12]. The radiographic differential diagnosis includes benign and malignant processes that cause lytic bone lesions as well as other soft tissue tumors [12] (Table 2). Although radiographic findings are helpful, open biopsy is necessary to make the diagnosis of IM. Complete excision is often curative, with a reported recurrence rate of 7 – 10% [3]. In the absence of visceral involvement, prognosis is excellent and spontaneous regression is commonly reported [12,13]. Once the diagnosis is made, observation is the treatment of choice [8]. Interval CT or other imaging study is not necessary unless clinical progression of disease is suspected. Resec.

tion of multiple lesions is not indicated unless functional impairment ensues or if vital organs are affected [8,12]. Patients with multicentric visceral involvement have a poor prognosis and usually succumb to cardiopulmonary or gastrointestinal complications [8].

References [1] F.M. Enzinger, S.W. Weiss, Infantile myofibromatosis: Solitary and multicentric types, in: F.M. Enzinger, S.W. Weiss (Eds.), Soft Tissue Tumors, 2nd ed., Mosby, St. Louis, 1988, pp. 171 – 178. [2] J.D. Williams, D. Schrum, Congenital fibrosarcoma, report of a case in a newborn infant, Arch. Pathol. 51 (1951) 548 – 552. [3] A.P. Stout, Juvenile fibromatosis, Cancer 7 (1954) 953 – 978. [4] E.B. Chung, F.M. Enzinger, Infantile myofibromatosis, Cancer 48 (1981) 1807 – 1818. [5] M.J. Rutigliano, I.F. Pollack, M. Ahdab-Barmada, D. Pang, A.L. Albright, Intracranial infantile myofibromatosis, J. Neurosurg. 81 (1994) 539 – 543. [6] C.M. Coffin, L.P. Dehner, Fibroblastic – myofibroblastic tumors in children and adolescents: A clinicopathologic study of 108 examples in 103 patients, Ped. Path. 11 (1991) 569 – 588. [7] G. Hartig, C. Koopmann, R. Esclamado, Infantile myofibromatosis: A commonly misdiagnosed entity, Otolaryngol. Head Neck Surg. 109 (1993) 753 – 757. [8] R.S. Davies, H. Carty, A. Pierro, Infantile myofibromatosis — a review, Br. J. Rad. 67 (1994) 619 – 623. [9] Y. Fukasawa, H. Ishikura, A. Takeda, et al., Massive apoptosis in infantile myofibromatosis: A putative mechanism of tumor regression, Am. J. Path. 144 (1994) 480 – 485. [10] M. Hasegawa, S. Kida, T. Yamashima, J. Yamashita, S. Takakuwa, Multicentric infantile myofibromatosis in the cranium: Case report, Neurosurgery 36 (1995) 1200 – 1203. [11] L.P. Burgess, J.J. Quilligan, R.D. Moe, et al., Congenital multiple fibromatosis (Infantile myofibromatosis), Arch. Otolaryngol. Head Neck Surg. 114 (1988) 207 – 209. [12] J.A. Queralt, V.C. Poirier, Solitary infantile myofibromatosis of the skull, AJNR 16 (1995) 476 – 478. [13] T.E. Wiswell, J. Davis, B.E. Cunningham, et al., Infantile myofibromatosis: the most common fibrous tumor of infancy, J. Ped. Surg. 23 (1988) 314 – 318.