Plexiform neurofibroma of the uterine cervix: a case report and review of the literature.

The female genital system is rarely affected in von Recklinghausen neurofibromatosis. The vulva is the most frequent genital location, but vaginal, cervical, uterine, and ovarian neurofibromas have rarely been reported. We describe a case of plexiform neurofibroma affecting the uterine cervix in a patient with chronic pelvic pain and menorrhagia who had multiple cutaneous neurofibromas and 1 large paraspinal neurofibroma. A small plexiform neurofibroma, which was not grossly visible, was confined to the uterine cervix and coexisted with a uterine leiomyoma and adenomyosis. There were no neurofibromas in the myometrium, fallopian tubes, or ovaries. Plexiform neurofibroma is a neoplasm that should be considered in the differential diagnosis of spindle cell neoplasms of the uterine cervix, especially in specimens from patients with neurofibromatosis. Neurofibromatosis involving the female genital tract is uncommon. The vulva is the most frequent genital organ affected, whereas involvement of the uterine cervix has been reported only rarely.12 We describe a case of localized plexiform neurofibroma of the uterine cervix in a patient with multiple cutaneous neurofibromas, 1 paraspinal neurofibroma, and a family history of neurofibromatosis, type 1 (NF1). Although neurofibromatosis can involve various gynecologic organs, to our knowledge, localized plexiform neurofibroma in the uterine cervix without involvement of other parts of the female genital tract has not been described. Pathologic findings showed the combination of adenomyosis, uterine leiomyoma, and uterine cervical neurofibromatosis, which probably led to the patient's uncontrollable pelvic pain and heavy menstruation. REPORT OF A CASE A 39-year-old black woman, gravida 6, para 4, with a 2-year history of heavy menstrual cycles and chronic pelvic pain, was admitted in 2004 to the obstetric and gynecologic service for definitive surgical treatment. The clinical diagnosis was symptomatic uterine leiomyomas and menorrhagia. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. She had multiple cutaneous scars from previously excised neurofibromas. Also, a large, 14 × 4 × 2-cm thoracic paraspinal neurofibroma from T4 to T9 extending into the neural foramina at T6–T7 had previously been neurosurgically resected. The patient had a family history of neurofibromatosis, and her last child had been born with ambiguous genitalia. Formal genetic testing had not been performed on the patient or her family members. PATHOLOGIC FINDINGS The specimen consisted of a uterus with attached cervix and both fallopian tubes and ovaries. The uterus measured 8 × 4.5 × 3.5 cm. The cervix measured 3 × 2.5 × 1.5 cm. The ectocervix was smooth. The cervical os was slit-shaped and measured 0.6 cm in greatest diameter. There were no gross deformities of the uterine cervix on the external surfaces. The endometrium measured 0.3 cm in maximum thickness. The myometrium measured 2.2 cm in maximum thickness and contained 1 white, firm, circumscribed nodule close to the serosal surface measuring 1 cm in greatest diameter. The fallopian tubes and ovaries were grossly unremarkable. Multiple sections of cervix, endocervix, endomyometrium, and both fallopian tubes and ovaries were submitted for histologic analysis. Microscopically, within the cervical stroma, there was a poorly demarcated nodule composed of numerous anastomosing fascicles of Schwann cells that separated smooth muscle bundles and extended among endocervical glands (Figure 1). Small nodules of Schwann cells were seen adjacent to endocervical glands (Figure 2). Structures resembling pacinian corpuscles were also present. Some of the anastomosing fascicles of Schwann cells showed myxoid areas, whereas others exhibited fibrosis. An S100 protein immunostain highlighted the fascicles of Schwann cells (Figure 3) as well as the small corpuscles (Figure 4). The myometrium showed adenomyosis and a leiomyoma. The leiomyoma was positive for smooth muscle actin and desmin and negative for S100 protein. Both fallopian tubes and ovaries were unremarkable. There were no neurofibromas in the myometrium, fallopian tubes, or ovaries. COMMENT The peripheral, or classical, type of neurofibromatosis (NF1) is inherited in an autosomal dominant pattern, affects 1 in 3000 live births, and is characterized by different types of mutations in the NF1 gene.23 Neurofibromas, the hallmark of NF1, may be found in essentially any site, including the gastrointestinal tract, blood vessels, heart, and larynx.3 Genitourinary involvement is very uncommon. Localized neurofibromas are the most common type of lesions in patients with NF1, and, histologically, they are no different from the solitary forms seen in patients without neurofibromatosis. Plexiform neurofibromas may be large, grossly distorting the nerve, and microscopically appear tortuous with expanded nerve branches. Diffuse neurofibromas are poorly circumscribed, infiltrate along connective tissue septae, and envelop normal structures with uniform fibrillary collagen bundles. The NF1 gene, a tumor suppressor gene residing on chromosome 17, spans 300 kilobases (kb) and is one of the largest known human genes.3 It encodes a protein called neurofibromin, which is widely expressed in various tissues, and may function as a negative regulator of intracellular ras signaling.34 The NF1 gene mutations, with a mutation rate among the highest in autosomal dominant diseases, encompass insertions, deletions, and point mutations. The less common, central type of neurofibromatosis (type 2, or NF2) is also autosomal dominant. It is characterized by bilateral acoustic schwannomas. The gene is located on chromosome 22.23 Patients with NF1 almost never develop acoustic schwannomas, the hallmark of NF2.3 Neurofibromatosis, type 1, may also present as such variants as segmental, gastrointestinal, familial spinal neurofibromatosis, or familial café au lait spots.23 These variants have incomplete or atypical features of NF1. The frequently negative family history, unaffected children, and confined locations suggest a somatic mutation instead of an inherited condition in these variants. Neurofibromatosis/Noonan syndrome, Watson syndrome, whole-gene-deletion phenotype NF1, mixed neurofibromatosis, and pigmented neurofibromas have also been reported.3 Extracutaneous neurofibromatosis occurs in less than 1% of patients with NF1.1 The gastrointestinal tract and urinary bladder are the organs most frequently involved in visceral presentations.1 The female genital system is rarely affected in neurofibromatosis. The vulva is the most common part of the female genital system to be involved.12 Clitoral neurofibromatosis may create ambiguous genitalia,35–7 and this may have been the cause of the ambiguous genitalia seen in the patient's last child. Vagina,128 myometrium,9 and ovary10 have occasionally been reported as sites of neurofibromas. We found only 5 cases of uterine cervical neurofibromas in the English literature (Table 1). In our case, the plexiform neurofibroma was confined to the uterine cervix and was not grossly visible. The patient has classic NF1 with multiple cutaneous and paraspinal nerve neurofibromas and a family history of neurofibromatosis, although she does not have café au lait spots. The neurofibroma of her uterine cervix, as well as adenomyosis and uterine leiomyoma, probably contributed to her chronic, unrelenting pelvic pain. The histologic differential diagnosis of neurofibroma of the uterine cervix is listed in Table 2. Despite its rarity, physicians should consider the possibility of genitourinary involvement in patients who have neurofibromatosis and unexplained chronic pain, bleeding, and distress symptoms. Copyright: College of American Pathologists 2005 Figure 1. Anastomosing fascicles of Schwann cells separate smooth muscle bundles of the uterine cervix (hematoxylin-eosin, original magnification ×150). Figure 2. A small nodule of Schwann cells is seen adjacent to an endocervical gland (hematoxylin-eosin, original magnification ×200). Figure 3. An S100 protein immunostain highlights the fascicles of Schwann cells within the cervical stroma (original magnification ×100). Figure 4. The S100 protein immunostain demonstrates small tactile corpuscles within the tumor (original magnification ×200) Contributor Notes Reprints: Marjorie R. Fowler, MD, Department of Pathology, Louisiana State University Health Sciences Center, PO Box 33932, Shreveport, LA 71130 ([email protected])