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Journal of Cancer Research and Therapeutics, Vol. 7, No. 1, January-March, 2011, pp. 78-80 Case Report "Very Late" isolated para-aortic nodal recurrence of carcinoma cervix mimicking radiation-induced sarcoma Sumeet G Dua1, Nilendu C Purandare1, Siddhartha Laskar2, Sneha Shah1, Kedar K Deodhar3, V Rangarajan1 1 Bioimaging Unit, Tata Memorial Hospital, Parel, Mumbai- 400 012, India Correspondence Address: V Rangarajan, Bio-Imaging Unit, Tata Memorial Hospital, Parel, Mumbai - 400 012, India, drvrangarajan@gmail.com Code Number: cr11017 PMID: 21546749 DOI: 10.4103/0973-1482.80470 Abstract Only a minority of the patients who develop recurrence after definitive treatment for cervical cancer are detected after 5 years (late recurrence); the numbers are lesser still after 10 years (very late recurrence). Among the infrequent cases that do develop "late" and "very late" recurrence, the commonest site is the pelvis. We report an unusually rare recurrence of treated cervical cancer confined to the para-aortic nodal group after a protracted disease-free interval of 13 years. On the basis of the long disease-free interval, location of the mass at the periphery of the radiation field, and aggressive imaging appearance, a diagnosis of radiation-induced sarcoma was considered. However, the final diagnosis of isolated para-aortic nodal recurrence of cervical cancer was rendered based on the histopathological and immunohistochemistry findings, supported by the absence of disease elsewhere on whole-body imaging.Keywords: Carcinoma cervix, isolated para-aortic nodal recurrence, para-aortic nodal recurrence, PET/CT, radiation induced sarcoma, recurrent carcinoma cervix, ′very late′ recurrence Introduction The commonest site of recurrence in patients treated for primary cervical cancer is the pelvis. However, in about 1.7% cases, the recurrence may be isolated and confined to the para-aortic nodal group with absence of disease in the pelvis and distant metastases. [1],[2],[3] In both the cases, most of the patients present within the first 2 years after treatment. Isolated para-aortic nodal recurrence occurring after 10 years has been scantily described in literature. On the other hand, second malignancies after receiving definitive treatment tend to occur after a prolonged disease-free interval. We present a "very late" recurrence of cervical cancer in a woman with an antecedent history of receiving definitive radiation therapy (RT) 13 years back. The unusually aggressive radiologic picture with destruction of lumbar vertebrae led us to think of radiation-induced second malignancy, a clinicoradiologic claim that was refuted by the histopathological findings. Case Report A 40-year-old woman (P2L2) presented to the gynecology clinic in the summer of 1997 with vaginal bleeding of 3-month duration. Clinical examination revealed an exophytic ulceroproliferative cervical mass with associated left parametrial induration. There was no underlying morbidity or medical disease. She had no history of receiving hormonal therapy. A punch biopsy was consistent with squamous carcinoma of the cervix. Computed tomography (CT) scan confirmed the clinical findings. There was no retroperitoneal adenopathy or liver metastasis. Infiltration of the left parametrium with mild left-sided hydronephrosis was noted. The clinicoradiologic diagnosis was stage IIIb carcinoma cervix. She received external beam radiotherapy (EBRT) to the dose of 50 Gy in 25 fractions over 5 weeks, followed by intracavitatory radiotherapy delivering a dose of 25 Gy at point A. The EBRT portal comprised of a standard anteroposterior-posteroanterior field using 60-cobalt gamma rays. The superoinferior extent of the portal was from the L4-L5 junction to the lower border of obturator foramen and the lateral borders extended 1.5 cm beyond the pelvic brim. At the first follow-up after completion of therapy, there was complete regression of the cervical mass on per vaginal examination and the parametria were supple. There was no clinicoradiological evidence of disease, confirmed also on vaginal cytology. The patient was followed up 3 monthly for the first year, 6 monthly for the next two years, and yearly thereafter till 5 years with clinicoradiological and cytological examination. In early 2010, she presented with backache and burning micturation for 3 weeks. A per-vaginal examination at this time revealed an unremarkable cervix which was flush with the vagina. Bilateral parametria were supple and the rectal mucosa was free. Pap smear cytology was normal. Ultrasonogram of the abdomen and pelvis revealed a heterogeneously hypoechoic retroperitoneal mass with left-sided hydronephrosis. A positron emission tomorgraphy (PET)/CT study revealed a hypermetabolic lobulated soft tissue mass in the retroperitoneum encasing the aorta and extending from L1 to L5 vertebral level with a satellite nodule at the level of T12 vertebra. The mass encased the left ureter with resultant ipsilateral hydronephrosis. Noteworthy was the erosion of the vertebral bodies of L3 and L2 by the retroperitoneal mass [Figure - 1]. There was no other focus of increased tracer uptake. The uterus and cervix were normal. No pelvic mass was identified. In keeping with aggressive radiologic appearance of the mass and a history of receiving RT about 13 years back, the foremost clinic-radiologic differential was a radiation-induced sarcoma (RIS), the commonest imaging appearance of which is a soft tissue mass with associated bone destruction occurring after a mean duration of 15.5 years. [4] The fact that the mass was located at the border of the field of radiation also supported the provisional diagnosis of RIS. A CT-guided biopsy of the mass was performed. Histopathological examination of the biopsied tissue however showed features of squamous cell carcinoma (SCC) [Figure - 2]a. Immunohistochemistry with cytokeratin showed positive staining, confirming the histopathological diagnosis [Figure - 2]b. Also, the PET/CT did not reveal any abnormality in the head and neck, urogenital tract, lungs and gastrointestinal tract, and other potential sites that could metastasize to the retroperitoneum. Accordingly, a diagnosis of "very late" metastatic isolated para-aortic nodal recurrence of cervical cancer was rendered. The patient was advised definitive RT to the recurrent para-aortic nodal mass and associated L1 to L5 vertebral bodies to the dose of 50 Gy/25 fractions using a 3-dimensional conformal radiotherapy technique in order to reduce dose to the normal structures. She is currently due for follow-up. Discussion Carcinoma of the cervix is one of the most common gynecological malignancies worldwide and the leading cause of cancer-related death in women in developing countries. [5] Radical hysterectomy or RT is the standard of care in treatment of early cervical cancer. In recent years, cisplatin-based chemotherapy has been added to RT in the treatment of advanced disease. Despite improved survival following addition of chemotherapeutic agents, recurrence rates continue to be high, particularly in advanced stages, and the prognosis of patients with recurrent cervical cancer remains dismal. [6] Recurrence is defined as tumor regrowth at the primary site or development of metastatic disease 6 months or more after completion of therapy. [7] Following initial treatment, about three-fourths of the recurrences are expected to occur within 2 years and more than 90% of the recurrences within 5 years. [6] A handful of studies have discussed "late" recurrence of carcinoma of the cervix, which is defined as recurrence after 5 years, and is seen only in about 0.4 to 7.5% cases. [1] Recurrence after 10 years ("very late" recurrence) is rarer still and was reported in less than 0.4% cervical cancer patients in two large recent studies [1],[8] which analyzed more than 2 500 patients. Among those who developed "late" and "very late" recurrence, the commonest site is the pelvis. [1],[8] Isolated recurrence of cervical cancer in the para-aortic nodal group, with no concomitant locoregional relapse or distant metastases, is infrequently seen. In the largest multi-institution study done so far to assess isolated para-aortic nodal recurrence, Niibe et al. [3] analyzed the details of more than 5 000 treated patients with cervical cancer and reported an incidence of less than 1.7%. Also noteworthy was that the maximum interval between treatment and recurrence was 109 months, with not a single case of recurrence seen after 10 years. Chou et al. [9] and Grigsby et al. [10] documented similar findings in smaller studies done earlier, with not a single case of isolated para-aortic recurrence occurring after 7 and 8 years, respectively. Recurrence of cervical cancer confined to the para-aortic nodes after a quiescence of 13 years, as seen in our case, is exceedingly uncommon and has not been reported earlier. Unique to the case was the erosion of the lumbar vertebrae by the nodal mass and the time elapsed since RT for the primary cervical cancer, which made the diagnosis of RIS more likely. Conventionally, Cahan′s criteria [11] have been used for defining radiation-induced second malignancies. The features of radiation-induced second malignancy as per Cahan′s criteria include the following: (1) malignancy at the periphery or outside the primary RT portal, (2) sufficiently long interval (7-10 years) between primary radiation and development of malignancy, and (3) histological type that is different from that of the primary lesion. Our current patient clearly fit into the category of RIS, but for the histopathology that revealed a "very late" nodal recurrence. Only about a third of the patients with isolated para-aortic nodal recurrence are symptomatic at presentation, low back ache being the commonest symptom. Also, the presence of symptoms at the time of recurrence correlates with poor overall survival. [9] This highlights the importance of early detection of recurrence, and the role of inclusion of tumor marker levels and cross-sectional imaging studies, in the follow-up, vis-à-vis conventional clinical examination with Pap smear cytology. Niibe et al. [3] showed a statistically significant correlation between SCC-antigen (SCC-Ag) level at the time of initial treatment and at the time of isolated para-aortic nodal recurrence; and between high serum SCC-Ag level at the time of isolated para-aortic nodal recurrence and coexisting symptoms. In recent years, the clinical and therapeutic impact of combined PET/CT has been investigated in patients with suspicion of recurrent cervical cancer and is being increasingly used in this setting. PET/CT is better than conventional cross-sectional imaging with CT or MRI and has shown to significantly impact clinical management and alter treatment strategies. [12] There are no set guidelines for the treatment of isolated para-aortic recurrence and studies have shown conflicting results with respect to the benefit of chemoradiotherapy vs radiotherapy alone in this setting. [3],[9] Our case thus highlights the importance of long-term follow-up of patients with treated cervical cancer, which as shown can recur after prolonged disease-free intervals, thereby confounding clinicoradiological interpretation. References
Copyright 2011 - Journal of Cancer Research and Therapeutics The following images related to this document are available:Photo images[cr11017f2.jpg] [cr11017f1.jpg] |
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