Photomicrograph of a solitary myofibroma of the hard palate. A suture marks a previous incisional biopsy site (patient 12).
Computed tomographic scan of a nasopharyngeal myofibroma demonstrating the lesion's heterogeneity, with evidence of calcification (patient 4).
Photomicrograph of a solitary myofibroma. Hematoxylin-eosin section shows proliferation of benign spindle cells arranged in interlacing fascicles with normal overlying epithelium (patient 12) (original magnification ×80).
Beck JC, Devaney KO, Weatherly RA, Koopmann CF, Lesperance MM. Pediatric Myofibromatosis of the Head and Neck. Arch Otolaryngol Head Neck Surg. 1999;125(1):39-44. doi:10.1001/archotol.125.1.39
To examine the clinical and pathological features of pediatric myofibroma of the head and neck and to discuss the challenges in diagnosis and treatment.
A retrospective search of pathology department and clinical records to identify patients with myofibroma and a retrospective review of English-language medical publications.
Academic medical center.
Thirteen pediatric patients (aged from birth to 8 years old) diagnosed as having myofibroma of the head and neck.
Nine of 13 patients were cured with conservative surgical excision. Four patients (31%) had recurrence, requiring multiple surgical procedures. One third showed spontaneous regression clinically or by histological examination. The clinical course did not parallel the histological appearance, as high cellularity and mitotic figures were commonplace among the specimens. A misdiagnosis of malignancy was not unusual in this series, as 3 patients had an initial diagnosis of fibrosarcoma, which on review was revised to myofibroma.
Myofibromatosis is a distinct disorder among the great number of fibrous proliferations occurring in infants and children, with a particular predilection for the head and neck region. These lesions should be clearly distinguished from conventional adult-type fibromatoses (desmoid tumors), which are more aggressive. Most patients have solitary lesions that respond well to conservative surgical excision, whereas a few of these lesions behave more aggressively, requiring several surgical procedures for the management of recurrent or persistent tumor. Many of these lesions show spontaneous regression, suggesting that lesions not affecting vital functions, resulting in growth anomalies, or demonstrating rapid aggressive growth may be managed conservatively.
THE FIBROMATOSES of childhood are a heterogeneous group of disorders characterized by the proliferation of fibroblasts, myofibroblasts, or both. Infantile myofibromatosis is a distinct clinical disorder characterized by solitary, multicentric, or generalized neoplasms of myofibroblastic origin. Myofibromas present as firm nodules of spindle-shaped cells involving the dermis, subcutaneous tissue, or soft tissues. Although previously considered rare, recent clarification of pathological criteria for the diagnosis of myofibroma has led to an increase in the frequency of this diagnosis. Many affected patients will present for care to an otolaryngologist–head and neck surgeon because about one third of tumors arise in the head and neck.
Of the several classifications of pediatric fibromatoses described in the literature, that of Enzinger and Weiss1 is most widely accepted. The desmoid fibromatoses are locally aggressive, recurring lesions, similar to the fibromatoses found in adults, and typically occur in the extremities or the trunk. In contrast, myofibromas are, in general, peculiar to infancy and childhood, having little or no clinical or morphologic counterparts in adult life.
Myofibromatosis was first described in 1954 by Stout2 as "congenital generalized fibromatosis," a term he chose to designate a disseminated disease of multiple nodular lesions in newborns. Stout3 is also credited with recognizing that the fibromatoses, although locally invasive, multicentric, and often aggressive, could be distinguished from fibrosarcoma, a malignant neoplasm with metastatic potential. For many years, the standard treatment of fibromatoses of all types was aggressive, wide local resection, based on a review by Conley et al4 of 40 cases of fibromatosis, including 10 children younger than 15 years. Subsequently, Chung and Enzinger5 argued for the classification of infantile myofibromatosis as a distinct lesion, based on its unique clinical and staining characteristics consistent with myofibroblastic origin.
The solitary form is now recognized as the most common presentation, typically as a rapidly growing, locally invasive mass. The tumor's histological features in patients with multicentric myofibromatosis are similar to those of solitary lesions, with both forms demonstrating necrosis and regression.1,5 Some authors report1,4,6 that these lesions tend to be locally aggressive, with infiltrative growth and a strong tendency to recur after excision, whereas other reports suggest a benign character with spontaneous regression. The overall prognosis is excellent, with the exception of generalized forms involving the viscera. The generalized form is most often seen in neonates and may be fatal due to the involvement of vital structures.
The microscopic appearance of these tumors often does not reflect the generally benign clinical characteristics. Histological features consistent with malignancy, such as local invasion, increased cellularity, rich vascularity, and extensive necrosis, are not uncommon. Neither metastasis nor malignant degeneration of myofibromas, however, has been reported. Enzinger7 postulated that highly cellular lesions in infants are more aggressive and more resistant to therapy, as opposed to the less cellular or fibrotic lesions, which were more differentiated and clinically more benign. Other reports1,8 suggest that the interpretation of biopsy specimens varies widely, depending on which portion of the tumor was sampled. Indeed, the pathological distinction between myofibromatosis, aggressive fibromatosis, and fibrosarcoma can be challenging, even for experienced pathologists.
The clinical management of these lesions has yet to be well defined, perhaps because of the variability of clinical presentation, the lack of extensive experience at any one medical center, and the histological difficulties with diagnosis. Case reports constitute a large portion of the available literature. Reviews of histopathological findings have been published, but consulting pathologists often do not know the clinical outcomes of patients discussed in the reviews. Treatment outcomes detailed in older clinical reviews combine those of myofibromatosis with other fibrous tumors. Herein we describe the clinical and pathological findings in 13 patients with myofibroma treated during 30 years and discuss the challenges in diagnosis and treatment.
The medical records of 130 pediatric patients (from birth to 18 years) admitted to the University of Michigan Hospitals, Ann Arbor, between 1975 and 1997 with a diagnosis of benign head and neck neoplasm were examined. Additional cases of myofibroma were sought through the pathology department archives. By these methods, 13 patients were identified as having a diagnosis of myofibroma. The ages of the patients in this series ranged from birth to 8 years, but 10 patients (77%) were younger than 2 years (Table 1). Two patients (patients 6 and 7 from Table 1) were described in detail in a previous report.9 Of the 13 patients, 8 were female.
The clinical data examined on each patient included the site and size of tumor at presentation and the presence or absence of multiple lesions. Additional studies comprising a patient's workup were evaluated, including laboratory data, radiographic studies, and further pathological studies such as special immunostaining. All patients were treated at our institution, and the specimens were reviewed by experienced head and neck pathologists. Additional consultations among pathologists resulting in a revised interpretation or the same diagnosis were examined. The modalities of treatment were reviewed, including observation, surgical management, radiotherapy, and chemotherapy. Documentation of tumor recurrence, the length of patient follow-up, and evidence of tumor regression as described by a gross shrinkage of the tumor or pathological evidence of massive cellular death and necrosis were also examined. Follow-up data were obtained from referring physicians when available. Approval for this project was obtained from the Institutional Review Board for Human Subject Research–Medical School at the University of Michigan.
To ascertain patients diagnosed as having myofibroma whose tumors may have initially been misdiagnosed as fibrosarcoma, the archival search was extended to include patients treated for fibrosarcoma. All medical records of pediatric patients identified by the University of Michigan Hospital Cancer Registry from 1954 to 1997 with the diagnosis of fibrosarcoma were reviewed. Of these 26 patients, most had primary tumors of the abdomen or extremities. Six of these patients had fibrosarcoma of the head and neck, and the youngest patient was 10 years old.
Nearly half of patients (6 of 13) in this series presented with a single dermal or subcutaneous nodule (Table 1). The remaining patients (7 of 13) exhibited a mass in the aerodigestive tract, including the oral cavity (Figure 1), oropharynx, or nasopharynx. No patients were identified with visceral involvement, and none of the patients had a family history of myofibroma.
In general, examination revealed a nontender, well-circumscribed mass. The presence of other symptoms correlated with the size and location of the mass. Patient 2 exhibited upper extremity weakness as a result of extension of tumor into the spinal canal, and a neonate (patient 4) exhibited symptoms of obstructive sleep apnea due to nasopharyngeal obstruction (Figure 2). One patient (patient 3) was initially thought to have a facial hemangioma because the central portion of the mass had begun to involute. The lesion was excised because of the cosmetic deformity, and pathological examination revealed myofibroma.
The most common presentation was a solitary lesion (10 of 13 patients). Three patients in this series had other lesions that probably represented secondary foci. Two patients (patients 3 and 6) had undergone skeletal surveys and were found to have small lucent extremity lesions that did not become symptomatic or require treatment. Patient 4, who initially presented with obstructive sleep apnea due to a nasopharyngeal myofibroma, was noted to have a 1×1-cm subcutaneous lesion of the right thigh. Local excision of the mass revealed the pathological diagnosis of "probable fibroma," with no evidence of recurrence after 3 years of follow-up.
Imaging studies were not routinely done on patients with dermal or subcutaneous lesions. Computed tomographic (CT) scans were obtained in 5 of 13 patients, including 4 patients with bony lesions and 1 with a large lesion of the left temple (patient 7). A CT scan of this patient revealed erosion through both inner and outer tables of the skull. The typical CT appearance of myofibromatosis was a heterogeneous mass with both multicystic and solid areas and occasional areas of bony remodeling or calcification (Figure 2). Skeletal surveys were obtained in 2 patients younger than 6 months (discussed earlier). Four patients (patients 4-7) underwent thoracic, abdominal, and pelvic CT scans to rule out visceral involvement, and the results of all studies were normal.
Laboratory evaluation was not routinely done, with the exception of preoperative electrolyte levels and complete blood cell counts.
Most nodules appeared grossly as distinct, circumscribed nodules with staining characteristics between fibroblasts and smooth muscle (Figure 3). Histopathological sections were examined by hematoxylin-eosin staining, and 3 specimens underwent immunostaining. All 3 specimens displayed the characteristic immunoprofile of myofibroma, consisting of positive immunoreactivity for vimentin and actin and negative immunoreactivity for desmin or S-100 protein.1 The specimens demonstrated characteristic spindle-shaped cells arranged in bundles or fascicles. There was great variability from low to high cellularity within each specimen. A few specimens demonstrated central areas of massive cell death and necrosis, consistent with regression. There were no pathological features consistent among the lesions that were predictive of recurrence.
Of 13 patients, 12 were treated with surgical excision, and 8 of those 12 patients underwent simple excision without recurrence. Four patients required several surgical procedures for the management of recurrent or persistent tumor. Patient 12 presented with a hard palate lesion displacing a maxillary molar that was initially managed at an outside institution by extraction of the tooth and incisional biopsy. According to the family, the remaining lesion continued to grow (Figure 1). The pathology slides were interpreted at the University of Michigan as myofibroma. Because of possible problems with malocclusion and the disturbance of erupting teeth, the persistent mass was excised 8 weeks after the original biopsy, and the patient has been without recurrence for 18 months.
Patient 8 presented with a large tumor of the infratemporal fossa with extension into the pterygomaxillary fissure, and patient 5 had a large nasal mass extending into the maxillary and ethmoid sinuses, including involvement of the cribriform plate. Because complete excision with wide margins in these patients would have led to substantial morbidity, subtotal resections were performed, with serial excisions of persistent disease. Despite the aggressive nature of both these tumors early in the course, both eventually resolved, and the patients are currently free of disease. Patient 8 had histological evidence of persistent myofibroma but was treated expectantly because of the presence of pathological features of tumor regression. In the opinion of the surgeon and pathologist, the lesion eventually involuted, and the patient has remained disease free for more than 4 years (C.F.K. and Kenneth D. McClatchey, DDS, MD, oral communication, April 1998).
Patient 10 exhibited an unusual clinical course, presenting at 8 months of age with a large lesion of the base of the tongue. She underwent excision but suffered recurrences at the primary site nearly yearly during the next 10 years, undergoing local reexcision each time. The last surgical specimen had features of high-grade malignancy, including increased cellularity and the presence of mitotic figures, differing significantly from the appearance of the previous tumor specimens. After a subsequent recurrence, she underwent 9 cycles of chemotherapy consisting of dactinomycin, vincristine sulfate, and cyclophosphamide. The tumor volume was dramatically reduced and then stabilized. A small persistent lesion was still present, but spontaneous regression ensued during the next year, and the patient is disease free after 3 years. A second patient (patient 2) was treated with the same chemotherapy regimen. Surgery was believed to be contraindicated for this patient, who presented at age 8 days with a large neck lesion extending into the spinal canal. This patient responded well to 3 cycles of chemotherapy and is free of disease.
Patient 4 underwent excision of a nasopharyngeal myofibroma at 1 month of age. The histological examination in this case demonstrated that nearly all margins had microscopic tumor, with significant necrosis in the central portion. This patient has been observed closely for 3 years by nasopharyngoscopy, biopsies, and serial CT scans, and the tumor has never recurred.
The average length of follow-up in this series was 39 months. Four patients (patients 1, 7, 8, and 9) were lost to follow-up but, when last seen, were without disease (as indicated in Table 1). The remaining 9 patients are currently without disease. None of the primary lesions were simply observed, but some clinical or histological evidence of regression was present in about a third of the patients.
Infantile myofibromatosis of the head and neck is reported as rare, but as pathologists become more familiar with its histological features, this disorder may be increasingly seen by otolaryngologist–head and neck surgeons. Both multicentric and solitary lesions may be inherited as an autosomal recessive or autosomal dominant disorder with variable penetrance, and a thorough family history should be obtained.10,11 Computed tomographic scans of the thorax and abdomen may be reserved for those patients suspected of having disseminated lesions. In the present series, skeletal surveys were obtained in 2 patients, both revealing suspicious lesions, but this finding did not change the clinical management in these patients.
The morbidity of myofibromatosis depends chiefly on the site of the lesion. Lesions in certain locations may never be diagnosed if they regress without causing symptoms. Conservative surgical excision is recommended for tumors that affect vital functions or cause growth anomalies, with the morbidity of the lesion weighed against the potential morbidity of resection. Of 13 patients, 9 (69%) were cured with conservative surgical excision alone, and 1 patient with a lesion extending into the spinal canal was cured with chemotherapy alone. In our series, none of the patients were managed by observation alone, with the exception of those having secondary lesions in the extremities. As a minimum, biopsy is necessary for diagnosis, and an incisional biopsy is likely to be inadequate if the persistent mass causes functional or cosmetic morbidity. The recurrence rate of 31% (4 patients) in this series reflects the unfavorable location of 3 tumors (infratemporal fossa, skull base, and tongue base), for which multiple subtotal resections were performed to avoid the morbidity of complete resection.
Both patients in whom chemotherapy was used for treatment in the present series had a substantial reduction in tumor bulk. The benefit of chemotherapy is difficult to evaluate because of the lack of large randomized trials and the tendency for the condition to regress spontaneously.12,13 Chemotherapy may be a viable option for patients with myofibroma that is causing significant morbidity.
Because of rapid proliferation and features of increased cellularity, rich vascularity, and extensive necrosis, these tumors can easily be misdiagnosed as malignant neoplasms. Even aggressive intravascular growth, a commonly seen feature, does not seem to carry adverse prognostic importance. Fibrosarcoma represents the most common misdiagnosis that could lead to unnecessary therapy with substantial morbidity. Fibrosarcoma of the head and neck has been reported to occur rarely in infants and children.8,14 The present study did not reveal a single case of this tumor in infants treated at our institution, and the youngest patient identified with fibrosarcoma in this series was 10 years old. Three patients in the present series were initially diagnosed as having fibrosarcoma, with subsequent revision of the diagnosis on reexamination by a second pathologist. Although fibrosarcomas and myofibrosarcomas have been described in the pediatric group, malignant lesions can be differentiated microscopically by invasive borders, a greater cellularity, and a pronounced degree of nuclear pleomorphism.15- 17 The diagnosis of fibrosarcoma in infants and young children should be evaluated with some skepticism and reviewed carefully, particularly if a large surgical resection is contemplated.
Conley et al4 reported on the aggressive nature of myofibroma among 40 patients and advised against conservative management. Most of their patients were adults and probably had desmoid fibromatoses as defined by Enzinger and Weiss.1 In contrast, the present series shows the infant and childhood type of myofibroma in which regression appears commonplace. In several case reports,12,18,19 tumors were described that underwent complete spontaneous regression. Fukasawa et al20 provided evidence for greatly increased cell apoptosis in 2 patients with myofibroma and proposed that spontaneous regression may be mediated by massive cell death.
Our data substantiate that myofibroma is usually a solitary lesion with relatively benign features that occasionally can become aggressive. Conservative surgical excision is recommended as primary management. Despite the early growth phase of rapid proliferation, tumor growth usually slows, and most lesions eventually demonstrate involution. Watchful waiting may be appropriate if the lesion does not affect the function or growth of neighboring vital structures. Factors triggering apoptosis and tumor regression in these lesions are unknown.
Accepted for publication September 9, 1998.
Presented at the 13th Annual Meeting of the American Society of Pediatric Otolaryngology, Palm Beach, Fla, May 13, 1998, and the Seventh International Congress of Pediatric Otorhinolaryngology, Helsinki, Finland, June 8, 1998.
We thank Brian Gastman, MD, University of Pittsburgh Medical Center, Pittsburgh, Pa, for his assistance with the initial chart review, and Kenneth D. McClatchey, DDS, MD, Loyola University Medical Center, Maywood, Ill, for his helpful suggestions and comments.
Reprints: Marci M. Lesperance, MD, Division of Pediatric Otolaryngology, Department of Otolaryngology/Head and Neck Surgery, University of Michigan Hospitals, F6905 Mott, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0241 (e-mail: firstname.lastname@example.org).