Hemangiopericytoma

Myofibromas are benign mesenchymal neoplasms of myofibroblastic origin. Most present as solitary lesions at any age, but the presentation of multiple lesions in newborns and infants is known as infantile myofibromatosis. Multicentric lesions commonly involve soft tissues and bone and may involve internal organs, where they are associated with an unfavorable prognosis. Solitary lesions involving the viscera are rare. We report a case of a 3-month-old male infant with a left testicular mass detected during an evaluation for suspected torsion. The patient underwent orchiectomy, revealing a nodular mass with grossly evident foci of necrosis. Histologically, the lesion exhibited small fascicles of plump eosinophilic, smooth muscle actin-positive spindle cells, alternating with larger areas of primitive cells with vesicular nuclei and scant cytoplasm arranged around a hemangiopericytoma-like vasculature. To our knowledge, this is the first report of a myofibroma localized within the testis.

(Arch Pathol Lab Med. 2005;129:1322-1325)

Infantile myofibromatosis is the most common fibrous disorder of infancy,1 with solitary and multicentric forms described.2 Lesions involving multiple organs are more common in girls and are characterized by nodules in soft tissues, skeleton, and internal organs.2 In cases with visceral involvement, myofibromatosis is associated with an unfavorable prognosis, with a 73% death rate from disease-related complications in the largest series.1 Conversely, solitary lesions of the disease are more common in boys, generally manifesting as a swelling or mass in the soft tissues of the head and neck, trunk, and upper extremities.2 Solitary lesions involving viscera have been rarely reported and appear to have an excellent prognosis if completely excised.3 Furthermore, myofibromas in soft tissues and bone tend to spontaneously regress during follow-up,2,4 and few lesions recur locally following excision, even if the excision is incomplete.1,2 Although these lesions have been described in the lung, heart, gastrointestinal tract, pancreas, and central nervous system, to date there are no reports of testicular myofibromas as single lesions or as part of multicentric disease. We therefore describe the clinicopathologic features of a unique case of solitary testicular myofibroma involving a 3-month-old infant and distinguish it from other pediatrie and mesenchymal testicular neoplasms.

REPORT OF A case

A 49-day-old male infant with unremarkable birth history and a 12-hour history of testicular swelling and irritability was brought to the emergency department by his parents. Physical examination disclosed an edematous scrotal sac that transilluminated. A subsequent scrotal ultrasound revealed an enlarged left testis with a 2.0 × 1.9-cm area of heterogeneous echogenicity, a small hydrocele, and a thickened scrotal wall. Minimal blood flow was observed within the testicle. The radiologie differential diagnosis favored acute or subacute torsion, although a testicular mass was noted as a possible, but less likely, option. The left testis was explored and found to be swollen and firm but not twisted, while the spermatic cord was dusky but not swollen or twisted. Bilateral orchiopexy was performed, and at subsequent follow-up visits during the next 1 ½ months, physical examination and repeat ultrasounds showed resolution of the swelling and increased blood flow within the left testicle. However, the testicular enlargement noted in the original ultrasound persisted, and an afetoprotein level of 92 ng/mL was obtained. These findings prompted a left inguinal orchiectomy when the child was 3 months old. An intraoperative pathologic consultation suggested a sex cord-stromal tumor (SCST).

PATHOLOGIC FINDINGS

Gross examination revealed an 8-g testis with attached spermatic cord measuring 4.0 × 2.3 × 1.8 cm in overall dimensions. The tunica albuginea appeared tan-pink and smooth, with a 1.6-cm attached portion of unremarkable skin. sectioning revealed a firm, well-circumscribed, focally necrotic, tan-gray mass measuring 2.4 × 1.8 × 1.7 cm (Figure 1, A). A thin rim of normal-appearing testicular parenchyma was present at the periphery of the mass. Grossly, the mass appeared confined to the tunica.

At low power, the mass exhibited a nodular growth pattern, with alternating light and dark regions (Figure 1, B). Higher magnification revealed a dimorphic population of neoplastic cells along with foci of hemorrhage and necrosis. The lighter areas were generally located peripherally but were occasionally seen haphazardly distributed throughout the lesion. They were characterized by fascicles of plump, myoid-appearing, spindle cells with elongated nuclei and abundant eosinophilic cytoplasm (Figure 2, A). The darker staining, more central areas were typified by nodules of primitive-appearing cells, with vesicular nuclei, minimal eosinophilic cytoplasm, and indistinct cell borders (Figure 3, A). Within this component, mitotic figures (≤5/10 high-power fields) (Figure 3, A) and focal bands of coagulative necrosis were observed. The regions containing more primitive cells displayed a prominent vascular network ranging from delicate, slitlike to dilated, angulated blood vessels, thus conveying a hemangiopericytoma (HPC)-like appearance (Figure 3, B). The lesion was confined by the tunica albuginea. Immunohistochemically, smooth muscle actin stained the spindle cells with more abundant cytoplasm strongly (Figure 2, B) and the more primitive-appearing cells focally and weakly. Stains for desmin and SlOO protein were negative in neoplastic cells.

COMMENT

Infantile myofibromatosis is now the preferred term for the entity initially designated congenital fibrosarcoma by Williams and Schrum5 in 1951 and renamed congenital generalized fibromatosis by Stout6 in 1954. The term infantile myofibromatosis was coined by Chung and Enzinger2 in 1981 and reflects the typically young age at onset of this disease and the myofibroblastic nature of the neoplastic cells.4,7 Although the disease may manifest as solitary or multiple lesions, with varying sites of involvement and sex predilection,2 the gross and microscopic appearances of myofibromas are essentially the same in all locations. Smith et al8 later introduced the term myofibroma to note that such lesions were most commonly solitary and not exclusively pediatrie. Characteristically, myofibromas are circumscribed masses with a low-power nodular growth pattern and, in some examples, centrally necrotic areas. At higher magnification, they show a biphasic pattern, consisting of fascicles of myoid-appearing spindle cells without atypia, alternating with primitive cells with vesicular nuclei, indistinct cell borders, and occasional mitoses.1,2,7 Immunohistochemical expression of vimentin and smooth muscle actin and a lack of desmin and SlOO protein are typical.9 As in the present case, the primitive cell component may also be organized around variable HPC-like vasculature.2

Despite the uniformly bland cytologie appearance of the proliferating cells in these lesions, potentially worrisome histologie features (including fingerlike extension of spindle cells into surrounding tissue, growth of neoplastic cells into vascular spaces, hemorrhage, coagulative necrosis, and variable mitotic activity) may lead to the mistaken diagnosis of fibrosarcoma in a subset of myofibromatosis cases.2 These alarming features may be found in soft tissue and skeletal examples.2,10 However, the clinical behavior of these lesions is solely determined by the pattern of involvement and not by any combination of histopathologic factors. Specifically, solitary and multiple lesions confined to soft tissues and bone have an excellent prognosis and tend to regress spontaneously,2,4 with local recurrence rates of 9% to 11% for solitary lesions and spontaneous regression of up to 60% for multicentric lesions without visceral involvement. In contrast, up to 75% of newborns and infants with multiple visceral lesions die, with signs of respiratory distress or diarrhea soon after birth.1,2 To our knowledge, no associated metastatic disease has ever been reported.

Limited data are available on the clinical outcomes of solitary visceral lesions such as the present case. Of the reported cases, most have occurred in newborns presenting with intestinal obstruction, for which the patients underwent successful surgery without recurrence up to 10 years after surgery.3 The present case, while sharing many of the morphologic findings common to all myofibromas, is significant in that, to our knowledge, it represents the first gonadal myofibroma ever reported. The unusual location of this lesion introduces important clinical, but limited histologie, differential diagnoses that include a spectrum of pediatrie testicular and mesenchymal diseases.

Clinically, germ cell neoplasms are the most common primary tumors of the testis in the first 2 decades of life; 50% to 60% manifest in the first 2 years. Among the germ cell tumors in this age range, yolk sac tumors and pure teratomas predominate.11 Although the varied distinctive histologie patterns and infrequent necrosis of yolk sac tumors make the morphologic differentiation from myofibroma a simple one, the frequency of yolk sac tumors and its association with elevated serum α-fetoprotein likely prompted surgical intervention in the present case. However, normal α-fetoprotein ranges in infants, such as our patient, are significantly higher than those in older patients, irrespective of the presence or absence of testicular pathologic conditions.12 Teratomas may also be suspected clinically, as they are the second most common testicular tumor in this age group and typically present as a unilateral scrotal mass in infancy and childhood. Fortunately, and unlike their counterparts in the adolescent period and beyond, testicular teratomas diagnosed in the first decade of life carry an excellent prognosis, without regard for the mature or immature aspects of the tumor. Characteristic gross findings of keratinous debris, teeth, or bone, coupled with microscopically identified tissue derived from the 3 germ cell layers,11 should make these lesions easily distinguishable from the lesions of myofibromatosis. Other germ cell neoplasms, including seminoma, embryonal carcinoma, choriocarcinoma, and mixed germ cell tumors, almost never occur in the infancy period.

An intraoperative consultation suggested that the present case was "suspicious for a sex-cord stromal tumor." This group of varied neoplasms resembles the specialized supportive structures of the gonads and accounts for 7% to 12% of all prepubertal testicular neoplasms, with most being diagnosed in children younger than 2 years.11 Given the frequency of these tumors, it is reasonable that the pathologist in the present case, having noted a "stromal"appearing neoplasm on frozen section, raised the possibility of SCST, rather than a much rarer or unreported diagnosis of benign or malignant mesenchymal neoplasm. However, with rare exceptions, such as Sertoli cell tumors with sarcomatoid features," SCST lack spindle cells. Furthermore, their immunohistochemical positivity for inhibin and the absence of myoid-appearing cells make SCST easily discernible from myofibroma.

The differential diagnosis of mesenchymal lesions that may clinically or histologically mimic myofibroma in other sites includes, among others, entities such as nodular fasciitis, fibrous histiocytoma, neurofibroma, and infantile fibromatosis. However, with the exception of a single case report of myxoid neurofibroma of the testis reported almost 30 years ago,14 none of these lesions has been identified in the male gonads, to our knowledge. Furthermore, the myxoid matrix and lack of HPC-like vasculature in nodular fasciitis, SlOO positivity of neurofibromas, prominent storiform growth and factor XIIIa positivity of fibrous histiocytoma, and lack of circumscription and necrosis in infantile fibromatosis help differentiate them from myofibroma.9 Interestingly, infantile HPCs, although not previously reported in the testis (to our knowledge), may bear remarkable similarity to the primitive component of myofibromas histologically, to the point that many cases originally diagnosed as HPC have been found on review to have focal, mature, actin-positive spindle cells like the ones seen in the lighter areas in our case. This has led some to suggest that these lesions represent the spectrum of maturity of a single entity."

Fibrous hamartoma of infancy is more likely to present in this general testicular site. It is an uncommon benign fibroblastic and myofibroblastic proliferation that typically occurs in the axillary or shoulder region of boys in their first 2 years of life, usually presenting as a solitary small, rapidly growing, soft-to-firm mass. About 20% of cases are congenital. Grossly, this process is poorly circumscribed, with firm gray-white tissue admixed with fat. Histologically, the lesion consists of several cell types, including fibroblasts, myofibroblasts, primitive mesenchymal cells, and haphazardly distributed fat. The following 3 tissue components are seen in varying proportions: (1) fibrous trabeculae or septae composed of spindle cells separated by collagen, (2) myxoid foci containing primitive round or stellate mesenchymal cells, and (3) interspersed mature fat. The lesion has an organoid pattern. Therefore, in contrast to myofibroma, fibrous hamartoma of infancy is triphasic rather than biphasic. Occasionally, fibrous hamartoma of infancy can occur in the genital region,15 where it mimics embryonal rhabdomyosarcoma clinically, although the pathologic features are distinct if the pathologist is aware of this presentation. The characteristic "organoid" pattern helps distinguish fibrous hamartoma of infancy from rhabdomyosarcoma and from infantile fibrosarcomas. Embryonal rhabdomyosarcomas are readily distinguished from fibrous hamartoma of infancy and from myofibroma by their differentiation toward skeletal muscle; thus, immunohistochemistry for skeletal muscle markers (eg, desmin, MyoDl, or myogenin) resolves any doubtful case. Infantile fibrosarcomas are characterized by sweeping fascicular growth and have neither a biphasic nor a triphasic growth pattern.

Sarcomatous entities demonstrating an HPC-like vascular pattern, such as primitive neuroectodermal tumors, mesenchymal chondrosarcomas, and poorly differentiated synovial sarcomas, may resemble the central portions of myofibroma in biopsy specimens. In these instances, an immunohistochemical panel of cytokeratins, SlOO protein, and CD99 may help clarify the diagnosis.9 Finally, common paratesticular lesions that should be considered include adenomatoid tumors, which may rarely extend to the testis but have unique morphologic structure dissimilar to that of myofibroma, and leiomyomas, which tend to be well circumscribed, lack the less-differentiated component of myofibroma, and demonstrate desmin positivity.

In summary, although yolk sac tumors, teratomas, and SCST are the most common testicular neoplasms in infants, our case introduces myofibroma as a lesion that may present as a unilateral testicular mass in this age group. This case, like previously reported solitary myofibromas, presented symptomatically, having been detected following an episode of subacute testicular torsion likely precipitated by the intragonadal mass. Most important, the tendency of myofibromas to regress in other sites and their generally benign clinical behavior warrant their consideration in an infant with this clinical presentation. If diagnosed on an excisional biopsy, further surgical intervention may be avoided, sparing the infant the physical and potential biologic effects of orchiectomy.

References

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Samson W. Fine, MD; North J. Davis, MD; Lawrence E. Lykins, MD; Elizabeth Montgomery, MD

Accepted for publication June 15, 2005.

From the Department of Pathology, Johns Hopkins University Hospital, Baltimore, Md (Drs Fine and Montgomery); Department of Pathology, Gainesville Regional Pathology Associates, Gainesville, Ca (Dr Davis); and Gainesville Urology, Gainesville, Ga (Dr Lykins). Dr Fine is now with Memorial Sloan Kettering Cancer Center, New York, NY.

The authors have no relevant financial interest in the products or companies described in this article.

Corresponding author: Samson W. Fine, MD, Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave C 505, New York, NY 10021 (e-mail: fines@mskcc.org).

Reprints not available from the authors.

Copyright College of American Pathologists Oct 2005
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