Lower extremity pain as initial presentation of cervical cancer

IntroductionThe diagnosis of bone metastases in cervical cancer deﬁnes ad-vanced disease with a median overall survival of b1year(Matsuyamaetal.,1989;Abdul-Karimetal.,1990).Themostcommonbonesaffectedare the lumbar spine and pelvis; distal extremity metastases are rare,accounting for b5% of bone metastases (Ratanatharathorn et al., 1994;Rangarajanetal.,2010).High-dosepalliativeradiotherapyprovidessig-niﬁcant symptomatic relief in approximately 67% of cervical cancer pa-tients(Matsuyamaetal.,1989).Theoverallclinicalandpersonalimpactofosseousfracturesforpatientshighlightstheimportanceofclearlyde-ﬁning the management plan for osseous metastases in gynecologicalcancers.We report a woman who presented with back and lower ex-tremity pain, ultimately found to have cervical cancer. Despite mul-timodal therapy, the patient passed away 3 months after her initialpresentation. This case report also reviews the biology of bone me-tastases and presents some emerging therapeutic options for thesescenarios.Case reportThe patient was a previously healthy 36-year-old nulligravidawoman who presented with isolated back and right leg pain (RLE)fortwoweeks.ImagingworkupincludedX-rayandmagneticresonanceimaging (MRI) of the spine, which demonstrated multiple vertebralbody lesions with spinal canal extension at the T6 level (Fig. 1A);Tc99m bone scan redemonstrated the multiple spine and RLE lesions,including a large, distal right femoral lesion (Fig. 1B). Distal right ex-tremity X-rays and MRI were obtained to exclude pathologic fractureat this site (Fig. 1C). An anterior cortex, lytic lesion with associatedsoft tissue component was seen, without associated fracture. A subse-quent FDG-PET/CT (Fig. 1D) of the abdomen and pelvis demonstratedmultiple organ lesions and lymphadenopathy. Because the etiology ofthepresumeddiffusemetastaticdiseasewasunclear,thepatientsubse-quently underwent a CT-guided, core biopsy of the femur. Pathologyrevealed sheets of undifferentiated pleomorphic neoplastic cells withhigh nuclear/cytoplasmic (N:C) ratio, prominent nucleoli and nu-merous mitotic ﬁgures (Figs. 2A–C). The tumor cells stainedstrongly for cytokeratin (AE1/3) (Fig. 2D) and negative for CK7/CK20, S100, HMB45, synaptophysin, chromogranin, estrogen re-ceptor (ER), progesterone receptor (PR), thyroid transcriptionfactor-1 TTF1, CA125, renal cell marker, and calretinin. Becausethe primary site was still unidentiﬁable, excisional biopsy of thefemur lesion was performed. Pathology showed rare areas ofsquamous differentiation among nestsoftumorcellsimmunore-active for p63 (Fig. 2E) and CK5/6 (Fig. 2 F), consistent with apoorly-differentiated squamous cell carcinoma from either thelung, head and neck or uterine cervix. A pelvic examination re-vealed a single 2-cm erosive lesion on her anterior cervix, and acervical biopsy demonstrated a moderately-to-poorly differentiat-ed squamous cell carcinoma.Zoledronic acid was administered to slow the progression of thebone metastases, and surgical excision and internal ﬁxation wereperformed to the femur. She also received palliative radiation therapy(20 Gy over 5 fractions to T4–T7 and 8 Gy in a single fraction toL5-sacrum). The patient received one cycle of systemic gemcitabine(1600 mg/m