Rhabdomyosarcoma

* Primary alveolar rhabdomyosarcoma (RMS) involving perineal skin is extremely rare, particularly in the infant age group. We report a case of an alveolar RMS in a newborn with abnormal symmetrical perineal overgrowth, causing ambiguous morphologic structure of the genitalia. Clinical and imaging studies were suggestive of Proteus syndrome with lymphatic malformation. Histologic examination of the mass showed cutaneous alveolar RMS with areas of embryonal and pleomorphic RMS features. Multiple superficially located, cystic-dilated spaces with loose edematous-mucoid hypocellular stroma gave a gross morphologic structure similar to that of lymphatic-type excrescences.

(Arch Pathol Lab Med. 2002;126:982-984)

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children, constituting 5% to 8% of all solid tumors in the pediatric population. It appears to have a bimodal distribution. In children between 2 and 6 years of age, the tumor has a propensity for the head and neck or the genitourinary region, whereas in adolescents between 14 and 18 years of age, it is predominately located in the paratesticular, trunk, and abdominal sites. Of the genitourinary region in younger girls, the tumor occurs in the vagina, cervix, and uterus, with occasional tumor extending into the urethra and labia. The most common RMS is the embryonal subtype, followed by the alveolar subtype. The latter subtype typically affects older children and young adults and frequently involves the extremities and perineal sites.1,2 There is, however, considerable overlap among the various subtypes, and a mixed form such as embryonal RMS with focal alveolar features is not uncommon. For staging and prognostic purposes, such mixed forms are always classified as the alveolar type. Nevertheless, to the best of our knowledge, RMS with mixed embryonal-alveolar features occurring in newborns with a dermal and subcutaneous involvement in the perineum has not been well documented. We report herein a case of cutaneous alveolar RMS, possibly congenital in nature, that presented in an unusual fashion and caused a clinical dilemma.

REPORT OF A CASE

The patient was a 7-month-old girl who was admitted for evaluation of painless abnormal bulky mass in the perineal region. The mass was first noted at 2 weeks of age on the pubic area, which slowly continued to grow in size. Multiple additional lymphatic-type excrescences became evident in the perineal and perianal area with some progression of the cutaneous changes in the pubic area (Figure 1).

She was a full-term neonate born to a 24-year-old mother. Her perinatal history was unremarkable. Except for 2 episodes of seizure with abnormal electroencephalographic findings during the first month of life, she was otherwise in good health. The findings of computed tomographic (CT) and magnetic resonance imaging (MRI) scans of the head were unremarkable.

Physical examination of the genitalia revealed marked symmetrical enlargement of the labia majora, labia minora, and clitoris with erythema, induration, and exaggerated regal folds (Figure 1). There was some skin breakage with evidence of Candida infection. The vaginal opening and anus appeared normal. Before this examination, vesicular lesions and papillary lymphatic-like lesions appeared in the perineal and perianal area. Because of the ambiguous morphologic features of the genitalia, she underwent urologic and endocrinologic workup, which showed normal female chromosome phenotype and normal serum testosterone, androstenedione, 17-hydroxycorticosteroid progesterone, and dehydroepiandrosterone levels. A CT scan of the pelvis indicated that the mass was mainly composed of fat, measuring approximately 12 X 7 X 3 cm, with numerous strands of density, possibly representing abnormal vessels. An MRI was also suggestive of lymphatic malformation with fatty infiltration into the pubic and suprapubic areas and toward the bladder. These clinical and imaging findings were thought to be suggestive of Proteus syndrome with perineal overgrowth.

The patient underwent extensive debulking, which included the entire mass on the clitoris and clitoral hood and a substantial portion of overgrowth of each labia with extensions into the supra pubic area. The findings at surgery were also consistent with lymphatic malformation. Tissues deep to the involvement of the pubic area appeared to be fatty infiltrate and lymphatic malformation.

PATHOLOGIC FINDINGS

The specimen consisted of several irregular fragments of soft tan tissues with rough, somewhat cerebroid-gyriform configuration of the overlying skin. Cut surface was pale tan, edematous, and homogenous with focal punctuated lesions in the superficial areas.

Histologic examination showed primarily sheets and cords of poorly differentiated small round and spindle cells with scanty cytoplasm, extending from the papillary to the deep reticular dermis and subcutaneous fat (Figure 2, A). Frequent mitosis and numerous vascular invasions were observed. Polypoid growth pattern containing cysticdilated spaces and loose edematous-mucoid hypocellular stroma was focally seen in periphery of the tumor, giving a "botryoid" morphologic appearance (Figure 2, B). In the center, there were more differentiated strap or ribbonlike cells with abundant eosinophilic cytoplasm and cross-striations consistent with rhabdomyoblasts (Figure 2, C, inset). Approximately 20% of tumor cells were arranged in an alveolar pattern with tumor cells lining the fibrous septa (Figure 2, C). They were intermingled with significantly pleomorphic, multinucleated giant cells with "wreathlike" nuclei. The myogenic nature of the tumor cells was supported by the positive reactions for vimentin, desmin, musclespecific actin, and myogenin. The Ki-67 labeling index was 37%.

COMMENT

The genitourinary tract is a common location for RMS in children. These tumors usually originate deep to the introitus, most commonly in the vagina and less commonly in the vulva and perineum.1 The most common histologic subtype is embryonal, which responds well to excision and chemotherapy with a survival rate of greater than 90%. The botryoid type, a gross, morphologic description meaning grapelike, is a variant of the embryonal form. Although most botryoid RMSs are found in mucosa-- lined hollow organs, a few of these may also be encountered in skin-covered surfaces such as the eyelid or the anal region. It is unusual to find the alveolar histologic subtype in the perineal region. To our knowledge, only 16 (14.5%) of 110 cases of this subtype involving the perineum, perianal, and perirectal region have been reported in the literature.3 Compared with the embryonal form, alveolar RMS carries a more aggressive clinical course and a poorer prognosis.4,5

Most RMS with pleomorphic tumor cells in the pediatric age group is not pleomorphic RMS but embryonal or alveolar RMS with pleomorphic cytologic features.6

Alveolar RMS should not be confused with the embryonal RMS or the botryoid variant. According to Schmidt et al,6 the diagnosis of alveolar RMS was entertained only in the presence of an alveolar growth pattern with loss of cellular cohesion and formation of the tumor giant cells, irrespective of the amount of alveolar tissue present in the specimen. Only by using this approach, Harms et al7 were able to demonstrate a statistically significant difference in survival between the embryonal and the alveolar subtypes, including the solid variant.

Alveolar RMS in the perineal location is predominantly seen in the adolescent age group. It characteristically presents as either a painless or mildly tender mass and is frequently misdiagnosed as a cyst of the Bartholin duct or a perirectal abscess.4 Our case was unusual not only in its presentation, but also in its cutaneous involvement. The polypoid areas containing dilated spaces in upper dermis mimicked lymphatic-type excrescences and were misinterpreted as lymphatic malformation in MRI and during surgery. Therefore, the presence of atypical granular or spongy tissue in the vulva or perineal area should remind one of RMS.

The fact that the lesion was initially noted in the second week of age suggests that the tumor may have occurred during prenatal life. Primary cutaneous alveolar RMS accounts for less than 1% of RMS and tends to rise in the skin of the face.6 Rare cases of congenital alveolar RMS either presenting with multiple rashes or multiple cutaneous metastases have been reported, most with dismal outcome.8-9 Our patient, with a multidisciplinary approach including wide resection and cyclic chemotherapy, has shown no evidence of active disease after a 6-month follow-up period. This is in keeping with the relatively better prognosis seen in congenital tumors, but also may be on account of the localized nature of this lesion, although a longer follow-up is necessary.

Proteus syndrome is a rare congenital disorder. It is characterized by a wide variety of deformities, namely malformations and overgrowth of soft tissue and bone. Verrucous epidermal nevi and characteristic cerebriform masses involving the plantar or palmer surfaces are not uncommon. Most subcutaneous masses are lipomatous, hamartomatous, and lymphangiomatous hamartomas.10-12 Congenital myopathies and maturational delay in muscle development have been seen in Proteus syndrome.10 However, RMS has never been reported to relate to the syndrome. Although CT and MRI scans of the lesion were suggestive Proteus syndrome and the ambiguous genitalia and seizure episodes have also been described in association with the syndrome, there is no clear evidence in our case to support that the perineal lesion is related to Proteus syndrome. Furthermore, lack of chromosome abnormality and the absence of other associated stigmata, such as macrodactyly, orthopedic deformity, and pigmented skin lesion, essentially preclude this diagnosis.

Clitoral enlargement is a symptom that deserves full attention and thorough evaluation. It may be the first indication of an endocrine or intersex disorder, but more importantly, it may indicate an underlying neoplastic process as well. Evaluation in such cases should include careful history and physical examination followed by steroid determinations and imaging studies. If indicated, histologic diagnosis should be performed since prompt assessment is essential for curative treatment.

References

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2. Maldonado A, Fradera J, Velez-Garcia E. Carcinocythemia in a patient with rhabdomyosarcoma. Bol Asoc Med P R. 1991;83:13-16.

3. Enzinger FM, Shiraki M. Alveolar rhabdomyosarcoma: an analysis of 110 cases. Cancer. 1969;24:18-31.

4. Copeland LJ, Sneige N, Stringer CA, Gershenson DM, Saul PB, Kavanagh Jj. Alveolar rhabdomyosarcoma of the female genitalia. Cancer. 1985;56:849855.

5. Imachi M, Tsukamoto N, Kamura T, Shigematsu T, Funakoshi K, Nakano H. Alveolar rhabdomyosarcoma of the vulva: report of two cases. Acta Cytol. 1991; 35:345-349.

6. Schmidt D, Fletcher CD, Harms D. Rhabdomyosarcomas with primary presentation in the skin. Pathol Res Pract. 1993; 189:422-427.

7. Harms D, Schmidt D, Treuner J. Soft-tissue sarcomas in childhood: a study of 262 cases including 169 cases of rhabdomyosarcoma. Z Kinderchir. 1985;40: 140-145.

8. Godambe SV, Rawal J. Blueberry muffin rash as a presentation of alveolar cell rhabdomyosarcoma in a neonate. Acta Paediatr. 2000;89:115-117.

9. Grundy R, Anderson J, Gaze M, et al. Congenital alveolar rhabdomyosarcoma: clinical and molecular distinction from alveolar rhabdomyosarcoma in older children. Cancer. 2001;91:606-612.

10. Sarnat HB. New insights into the pathogenesis of congenital myopathies. J Child Neurol. 1994;9:193-201.

11. Hachich N, Lopez E, Baunin C, Olives JP, Armelin I, Bonafe JL. Proteus syndrome tin French]. Ann Dermatol Venereol. 1993;120:445-447.

12. Samlaska CP, Levin SW, James WD, Benson PM, Walker JC, Perlik PC. Proteus syndrome. Arch Dermatol. 1989;125:1109-1114.

Yun Gong, MD; Jerome Chao, MD; Bruce Bauer, MD; Xiaoping Sun, MD; Pauline M. Chou, MD

Accepted for publication November 5, 2001.

From the Departments of Pathology (Drs Gong, Sun, and Chou) and Plastic Surgery (Drs Chao and Bauer), Children's Memorial Hospital, Northwestern University Medical Center, Chicago, Ill.

Reprints: Pauline M. Chou, MD, Department of Pathology, Children's Memorial Hospital, Box 17, 2300 Children's Plaza, Chicago, IL 60614 (e-mail: pmchou@northwestern.edu).

Copyright College of American Pathologists Aug 2002
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