Gynecologic Oncology 98 (2005) 498 – 501 www.elsevier.com/locate/ygyno
Case Report
Extraskeletal myxoid chondrosarcoma: A report of a gynecologic case Mildred R. SantaCruza,*, Lori Proctorb, David B. Thomasb, Paola A. Gehriga a
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of North Carolina, 4013-B Old Clinic Building, Chapel Hill, NC 27599, USA b Department of Pathology, University of North Carolina, Chapel Hill, NC 27599, USA Received 27 December 2004 Available online 1 July 2005
Abstract Background. Extraskeletal myxoid chondrosarcoma is a rare tumor that has been reported and discussed in neurosurgical, orthopedic, and otolaryngologic literature. We report a case of vulvar extraskeletal myxoid chondrosarcoma. Case. This is a case of a 46-year-old woman who presented with a soft tissue mass in the left vulva and underwent local excision. Grossly, the tumors appeared to be leiomyomas. Pathology revealed an extraskeletal myxoid chondrosarcoma. Conclusion. We report the first case of an extraskeletal myxoid chondrosarcoma arising in the vulva. D 2005 Elsevier Inc. All rights reserved. Keywords: Extraskeletal myxoid chondrosarcoma; Pelvic sarcoma; Vulvar cancer
Introduction Pelvic sarcomas in the female patient are rare tumors, comprising less than 5% of all uterine cancers, less than 3% of vulvar cancers, and less than 2% of vaginal malignancies. The worldwide incidence of these sarcomas is 1– 3.3 per 100,000 women. The most common pelvic sarcoma is uterine corpus carcinosarcoma, arising from the endometrium, followed by uterine leiomyosarcoma. Although these occur with less frequency than pelvic carcinomas, their behavior has been well studied. These uterine sarcomas are known to be locally aggressive and have a propensity for metastasis. They are associated with a poor prognosis, having a 5-year survival of less than 10%. Vulvar cancers comprise less than 5% of gynecologic malignancies. Vulvar sarcomas are extraordinarily rare with the histology typically consisting of leiomyosarcomas or rhabdomyosarcomas. The prognosis associated with vulvar sarcoma is poor. Long-term survival is rare but has been achieved with aggressive surgical resection. Adjuvant * Corresponding author. Fax: +1 919 966 5670. E-mail address:
[email protected] (M.R. SantaCruz). 0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2005.04.045
chemotherapy and radiation therapy are recommended, though of limited benefit. Other rare vulvar sarcomas have also been described; however, to our knowledge, a report of extraskeletal myxoid chondrosarcoma of the vulva has not been published. Extraskeletal myxoid chondrosarcoma is a rare tumor that is most commonly located in the deep soft tissues of the lower extremity and buttock [1]. Other locations such as the upper extremity, shoulder, neck, orbit, and intraabdominal wall have also been reported [1 –3]. We report here a case of vulvar and periclitoral extraskeletal myxoid chondrosarcoma.
Case report A 46-year-old African American woman presented to her primary gynecologist with complaints of vulvar pain and a bulging mass that had persisted over a 4-month period. She was referred to Gynecologic Oncology for consultation. On physical examination, three separate masses were palpable in the left vulva and periclitoral region and noted to be smooth, well circumscribed, and mobile. MRI revealed
M.R. SantaCruz et al. / Gynecologic Oncology 98 (2005) 498 – 501
three separate ‘‘cysts’’ in the left vulva and paravaginal tissue, the largest being 2 cm in size. A fine needle aspirate of the vulvar mass was performed and interpreted as a possible spindle neoplasm. The patient was taken to the operating room and underwent excision of three masses, ranging from 1.5 1.5 1.5 to 7.0 2.7 1.9 cm in size. They were located deep to the left labium majus in the ischial fossa extending to the pubic ramus laterally and deep to the clitoris superiorly and medially. The tumors were smooth and well circumscribed, grossly similar to uterine leiomyomas. They were excised in full, preserving the clitoris, vagina, and overlying vulvar tissue. The patient convalesced from surgery without postoperative complications. Staging bone scan and chest radiographs were negative immediately following surgery. She is currently 6 months out from her diagnosis and is without evidence of recurrent disease.
Pathology The left labial masses consisted of two soft tissue nodules, ranging in size from 2.0 cm up to 7.0 cm in greatest gross dimension. The periclitoral mass consisted of a round soft tissue nodule with a maximum diameter of 1.5 cm. The external surface of each nodule was glistening and smooth with dense fibrous encapsulation. The cut surface revealed a gelatinous tan tumor dissected by fibrous bands, dividing the tumor into distinct lobules. Areas of gross hemorrhage were present. Representative sections were submitted for routine histologic evaluation. The hematoxylin and eosin stained slides revealed a sharply circumscribed, lobulated tumor with a distinct fibrous pseudocapsule (Fig. 1). The tumor formed an expansile moderately cellular mass composed of delicate bland spindled cells growing in a fine lace-like pattern. The neoplastic cells showed round to elongate nuclei, vesicular chromatin, inconspicuous nucleoli, and delicate
Fig. 1. This low magnification image illustrates the well-circumscribed tumor and its fibrous pseudocapsule.
499
Fig. 2. Medium power view shows intratumoral hemorrhage and hematazoin deposition.
bipolar cytoplasmic processes with indistinct cellular borders. Hemorrhagic foci with hemosiderin deposition and hematazoin were present (Fig. 2). Prominent myxochondroid stroma separated individual cells (Fig. 3). Rare mitotic figures were identified (less than 2 mitotic figures per 10 high power fields). The myxoid stroma was strongly positive with mucicarmine, while the tumor was diffusely immunoreactive for vimentin. Both CD31 and CD34 immunostains highlighted interspersed blood vessels. An S-100 was negative within the neoplastic cells. The differential diagnosis for this tumor was quite varied, however, we favored an extraskeletal myxoid chondrosarcoma based on the morphology, histology, and immunohistochemical staining. Irrespective of anatomic location, extraskeletal myxoid chondrosarcoma (EMC) is characterized as a multinodular well circumscribed pseudoencapsulated lesion composed of malignant round to spindle cells in cords and clusters set within a prominent chondromyxoid matrix [4]. Occasionally, the malignant cells may take on a more epithelioid appearance. Despite the designation as a
Fig. 3. High power image of spindle cells in cords set within chondromyxoid matrix. The cells have vesicular chromatin with inconspicuous nucleoli and indistinct cellular borders.
500
M.R. SantaCruz et al. / Gynecologic Oncology 98 (2005) 498 – 501
chondrosarcoma, histogenetic derivation from cartilage has not been proven. Vimentin, an intermediate filament expressed in cells of mesenchymal origin, is the only marker consistently expressed in EMC [5] as seen in our case. Immunohistochemical studies for S-100 protein, a nerve sheath differentiation marker, yield variable immunoreactivity within the neoplastic cells, while neuroendocrine markers, synaptophysin and nonspecific enolase, have been reported in some tumors [6]. Additionally, more than half of all cases of EMC have been associated with the reciprocal translocation t(9;22)(q22;q12) [7]. A second translocation involving t(9;17)(q22;q11) has been identified and occurs with less frequency than t(9;22)(q22;q12) [6]. Other pathologic considerations in the differential diagnosis of soft tissue chondromyxoid and myxoid lesions include chondromyxoid fibroma, juxtacortical (paraosteal) chondrosarcomas, chordoma, mixed tumors of salivary gland origin (pleomorphic adenoma) and adnexal origin (chondroid syringoma), as well as predominantly myxoid lesions such as aggressive angiomyxoma, low-grade myxofibrosarcoma, and low-grade fibromyxoid sarcoma. Chondromyxoid fibroma is a benign cartilaginous primary neoplasm of bone, usually involving long bones around the knee joint or the flat bones of the pelvis or ribs. It rarely occurs in a periosteal or soft tissue location. The tumor shows multilobulation with peripheral hypercellularity. The cells are spindled, show greater pleomorphism, and may be multinucleated. The stroma is predominantly myxoid with areas of hyaline cartilage and foci of calcification or ossification [8]. Juxtacortical (paraosteal) chondrosarcomas show broad attachment to the perichondrium or periosteum of the involved bone with soft tissue extension present in large lesions. The tumors show abundant chondroid matrix but lack the myxoid component [5]. The cytologic atypia of the chondrocytes displays a range from mild to moderate to marked. Chordoma, particularly the chondroid variant, typically occurs in sites such as the sacrococcygeal region, sphenooccipital region, or cervical spine. Chordomas appear as lobulated tumors, with the neoplastic cells growing in cords or sheets set within abundant myxoid stroma. Cells often contain cytoplasmic vacuolation, yielding the classic ‘‘physaliferous cells.’’ Chordomas are immunoreactive for S-100 protein, cytokeratin, epithelial membrane antigen (EMA), and vimentin. Positive staining for nonspecific enolase (NSE) has been reported; however, the chondroid component was negative for NSE in all cases [9]. Deep soft tissue mixed tumors of salivary gland origin (pleomorphic adenoma) and adnexal origin (chondroid syringoma) are rare [10]. These tumors contain both epithelial and myoepithelial components, a feature reflected in their immunoprofile. Immunohistochemical stains for epithelial markers, such as cytokeratin, and myoepithelial markers, such as S-100 protein and calponin, are expressed by their respective lesional component [5].
Aggressive angiomyxoma has been well documented within the soft tissue tumor literature occurring in the genital region, perineum, and pelvis. The vulva of reproductive aged females is a favored site of occurrence where angiomyxoma may be clinically mistaken for a Bartholin’s cyst, periurethral cyst, or hernia [11]. Angiomyxomas are characterized by a lobulated, partially encapsulated gelatinous architecture composed of spindle to stellate cells within a collagen-rich myxoid stroma. Variably sized thickor thin-walled vessels are dispersed throughout the stroma [12]. Mast cells are conspicuous. Angiomyxomas display diffuse immunoreactivity for vimentin, as well as muscle markers smooth muscle actin and muscle-specific actin. The neoplastic cells are negative for S-100 protein and cytokeratins [11]. Angiomyxomas lack the chondroid appearance of the stroma seen in EMC. Additionally, neither the reciprocal t(9;22)(q22;q12) or t(9;17)(q22;q11) have been reported in angiomyxomas. Aggressive angiomyxomas have a tendency for local recurrence [12,13]. Low-grade myxofibrosarcoma (formerly termed myxoid variant of malignant fibrous histiocytoma) typically occurs in the extremities of elderly patients, forming a multinodular gelatinous mass. Lesions are hypocellular and composed of spindle cells within abundant myxoid matrix with curvilinear capillaries [14]. Vimentin shows diffuse strong immunoreactivity. Despite the multinodular architecture and myxoid matrix, myxofibrosarcoma lacks the chondroid stromal appearance, as well as the translocations previously described that are seen in EMC. Low-grade myxofibrosarcoma has a propensity for multiple local recurrences [15]. Low-grade fibromyxoid sarcoma occurs in young to middle-aged adults as a deep-seated soft tissue mass, usually arising in the lower extremity. Lesions appear grossly well circumscribed; however, at the microscopic level, extensive soft tissue infiltration is often present. The neoplastic cells are bland spindle-shaped and distributed throughout an alternating fibrous and myxoid stroma, lacking hemorrhage and necrosis. The neoplastic cells show diffuse strong immunoreactivity for vimentin. Focal staining for smooth muscle actin and muscle-specific actin may occur. Lowgrade fibromyxoid sarcoma has a high rate of local recurrence and pulmonary metastases [16]. In contradistinction to EMC, low-grade fibromyxoid sarcoma shows a characteristic alternating fibrous and myxoid stroma and lacks the chondroid appearance of EMC. Additionally, the genetic translocations of EMC are absent in low-grade fibromyxoid sarcomas.
Discussion Extraskeletal myxoid chondrosarcoma has most commonly been described in the fields of neurosurgery, otolaryngology, and orthopedics. Enzinger and Shiraki first reported extraskeletal myxoid chondrosarcoma in 1972, defining it as a separate pathologic entity [2]. These tumors
M.R. SantaCruz et al. / Gynecologic Oncology 98 (2005) 498 – 501
are more common in men and are most often found in the lower extremity or hip region [1]. Their tendency is to locally recur with occasional distant metastasis to the lungs. Antonescu et al., in their review of twenty patients with extraskeletal chondrosarcoma, state that only five patients were without evidence of disease at the time of their report. Two of these five had only been followed for a total of 4 months since their initial diagnosis. The other 75% of the patients had local recurrence, metastatic recurrence, or both. Eleven of the fifteen patients with metastatic disease had lung involvement [1]. Orbital and intra-cranial EMC have also been described in the literature with similar results in recurrence and metastasis [3]. One report revealed local recurrence to the orbit twice, initially after complete macroscopic resection and again after complete excision with adjuvant radiation therapy [3]. Prognosis is fair, with greater than 80% 5-year survival in some reports [17,18]. However, many suggest that EMC is aggressive, resulting in 35 –50% mortality within 5 years and an average diseasefree interval of 20 months [1]. Disease has been reported to recur up to 8 years out from diagnosis [1]; thus, long-term follow up is suggested. EMC has previously been reported to respond to high-dose radiation while being poorly responsive to adjuvant chemotherapy [3,19]. Although no report has been published noting a gynecologic case of extraskeletal myxoid chondrosarcoma, we suspect that this particular case would behave in a manner similar to the multiple other reports of deep soft tissue EMC. At the time of final diagnosis, re-excision of the tumor bed was recommended in order to obtain wider margins; however, the patient declined further surgery. Postoperative radiotherapy was not felt to be indicated secondary to the conflicting literature regarding efficacy. This patient is undergoing frequent surveillance with pelvic examinations and with pelvic MRI and chest radiographs to evaluate for possible recurrence.
References [1] Antonescu CR, Argani P, Erlandson R, Healey J, Ladanyi M, Huvos AG. Skeletal and extraskeletal myxoid chondrosarcoma: a comparative clinicopathologic, ultrastructural, and molecular study. Cancer 1998;83:1504 – 21. [2] Gaudier F, Khurana JS, Dewan S, Shen T. Fine-needle aspiration cytology of intrabdominal wall extraskeletal myxoid chondrosarcoma:
[3]
[4]
[5]
[6]
[7]
[8] [9]
[10] [11]
[12]
[13]
[14]
[15]
[16]
[17] [18] [19]
501
a case report and review of the literature. Arch Pathol Lab Med 2003;127:1211 – 3. Khouja N, Smor S, Jemel H, Kchir N, Boussen H, Khaldi M. Mesenchymal extraskeletal chondrosarcoma of the orbit: report of a case and review of the literature. Surg Neurol 1999;52:50 – 3. Lucas DR, Heim S. Extraskeletal myxoid chondrosarcoma. In: Fletcher C, Unni KK, Mertens F, editors. Tumours of Soft Tissue and Bone. Oxford University Press. p. 213 – 5. WHO Classification of Tumours, Pathology and Genetics. Weiss SW, Goldblum JR. Extraskeletal myxoid chondrosarcoma. In: Weiss SW, Goldblum JR, editors. Enzinger and Weiss’s soft tissue tumors, 4th ed, p. 1368 – 79. Harris M, Coyne J, Tariq M, Eyden BP, Atkinson M, Freemont AJ, et al. Extraskeltal myxoid chondrosarcoma with neuroendocrine differentiation: a pathologic, cytogenetic, and molecular study of a case with a novel translocation t(9;17)(q22:q11.2). Am J Surg Pathol 2000; 24:1020 – 6. Hirabayashi Y, Ishida T, Yoshida MA, Kojima T, Ebihara Y, Machinami R, et al. Translocation (9;22)(q22;q12). A recurrent chromosome abnormality in extraskeletal myxoid chondrosarcomas. Cancer Genet Cytogenet 1995;81:33 – 7. Macdonald D, Fornasier V, Holtby R. Chondromyxoid fibroma of the acromium with soft tissue extension. Skelet Radiol 2000;29:168 – 70. Sell M, Sampaolo S, Di Lorio G, Theallier A. Chordomas: a histological and immunohistochemical study of cases with and without recurrent tumors. Clin Neuropathol 2004;23:277 – 85. Adachi T, et al. Mixed tumor of deep soft tissue. Pathol Int 2003;53:35 – 9. Bigotti G, Coli A, Gasbarri A, et al. Angiomyofibroblastoma and aggressive angiomyxoma: two benign mesenchymal neoplasms of the female genital tract: an immunohistochemical study. Pathol Res Pract 1999;195:39 – 44. Granter SR, Nucci MR, Fletcher CDM. Aggressive angiomyxoma: reappraisal of its relationship with angiomyofibroblastoma in a series of 16 cases. Histopathology 1997;30:3 – 10. Steeper TA, Rosai J. Aggressive angiomyxoma of the female pelvis and perineum: report of nine cases of a distinctive type of gynecologic soft-tissue neoplasm. Am J Surg Pathol 1983;7:463 – 75. Weiss SW, Goldblum JR. Malignant fibrous histiocytoma: myxoid type. In: Weiss SW, Goldblum JR, editors. Enzinger and Weiss’s soft tissue tumors, 4th ed, p. 550 – 8. Huang HY, Lal P, Qin J, Brennan MF, Antonescu CR. Low-grade myxofibrosarcoma: a clinicopathologic analysis of 49 cases treated at a single institution with simultaneous assessment of the efficacy of 3tier and 4-tier grading systems. Hum Pathol 2004;35:612 – 21. Weiss SW, Goldblum JR. Fibrosarcoma: fibromyxoid type. In: Weiss SW, Goldblum JR, editors. Enzinger and Weiss’s soft tissue tumors, 4th ed, p. 425 – 31. Enzinger FM, Shiraki M. Extraskeletal myxoid chondrosarcoma: an analysis of 34 cases. Hum Pathol 1972;3:421 – 35. McGrory JE, Rock MG, Nascimento AG, Oliveira AM. Extraskeletal myxoid chondrosarcoma. Clin Orthop 2001;382:185 – 90. Hitchon H, Nobler MP, Wohl M. The radiotherapeutic management of chordoid sarcoma. Am J Clin Oncol 1990;13:208 – 13.
