Recurrence in skeletal muscle from squamous cell carcinoma of the uterine cervix: a case report and review of the literature
© Ferrandina et al; licensee BioMed Central Ltd. 2006
Received: 25 April 2006
Accepted: 27 June 2006
Published: 27 June 2006
The occurrence of skeletal muscle metastases is a very rare event. Only two cases of late skeletal muscle recurrence from cervical cancer have been documented until now.
A 38-year old patient, submitted to radical hysterectomy and pelvic lymphadenectomy for a squamous FIGO stage IB1 cervical carcinoma, presented after 76 months with a palpable, and painless swelling on the left hemithorax. MRI showed a nodule located in the context of the intercostal muscles. Pathology revealed the presence of metastasis of squamous cell carcinoma of similar morphology as the primary. On the basis of FDG-PET findings, which excluded other sites of disease, surgical excision of the lesion was performed. The patient was triaged to chemotherapy plus external radiotherapy.
A case of skeletal muscle recurrence from cervical cancer after a very long interval from primary diagnosis is reported. Muscular pain or weakness, or just a palpable mass in a patient with a history of cancer has always to raise the suspicion of muscle metastasis.
The incidence of skeletal muscle metastases is reported to be less than 1% of metastases of haematogenous origin, despite the fact that skeletal muscle accounts for nearly 50% of the total body weight and is characterized by a rich blood supply . The reasons for the rarity of metastatic involvement of skeletal muscle are still unclear, but several hypotheses have been made including: a) the constant movement of skeletal muscles, which may represent a difficult condition for the implantation and growth of metastatic cells under the high tissue pressure related to the exercise associated increase of blood flow; b) the local production of lactic acid, which would create an unfavourable environment for metastatic cell growth; c) the inhibition of cell invasion by protease inhibitors located in the basement membrane; d) the antitumor activity of lymphocytes and/or natural killer cells within the skeletal muscle; e) in vivo evidences that skeletal muscle-delivered peptidic factors may influence the metastatization process . Psoas, iliopsoas and paraspinal muscles, and proximal musculature of the upper and lower limbs, represent the most frequently involved sites. Malignancies known to frequently metastasize to the muscle are melanoma, kidney, lung, thyroid cancer; moreover skeletal muscle metastases have been also reported in lymphoma, leukaemia and colon cancer patients .
To our knowledge, five cases of skeletal muscle metastasis and two cases of skeletal muscle recurrence after 24 and 60 months fro initial diagnosis of cervical cancer have been documented until now [2–9].
We report an unusual case of isolated intercostal muscle recurrence after a very long interval from primary diagnosis of squamous cervical cancer. A review of the literature with particular emphasis on the diagnostic and therapeutic issues is also presented.
A 38-year old patient was admitted to the Gynaecologic Oncology Unit of the Catholic University of Rome in June 1998 for irregular vaginal bleeding. Gynaecological examination revealed an ulcerated lesion (maximum diameter = 3 cm) of the uterine cervix The histopathologic diagnosis of colposcopy-guided biopsy revealed the presence of moderately differentiated squamous cell cervical carcinoma. The patient was clinically staged as having FIGO stage IB1 cervical cancer and was submitted to radical hysterectomy and pelvic lymphadenectomy. Final staging was pT1bN0M0 according to TNM classification.
After extensive counselling, the patient was triaged to combined chemotherapy with carboplatin (5AUC) and paclitaxel (175 mg/m2), plus external radiotherapy (total dose = 4,000 cGy in 20 fractions) on the left hemi thorax. After two months from the completion of treatment, the patient shows no evidence of disease and does not complain of any symptom related to radiation treatment.
Characteristics of cervical cancer patients with skeletal muscle involvement, as reported in the literature
Primary tumor histotype
Interval from primary tumor (months)
Clinical outcome (after diagnosis of metastasis)
Chemotherapy followed by radiotherapy
DOD after 3 months
Chemotherapy + radiotherapy
Bar Dayan 
Intralesional chemotherapy followed by radiotherapy
DOD after 4 months
ED at time of publication
Lost to follow up
NED after 30 months
Metastasectomy followed by chemotherapy + radiotherapy
NED after 8 months
Establishing the diagnosis of skeletal muscle metastasis sometimes can be difficult: indeed, although skeletal muscle metastases can be painful or palpable or cause deformity according to location, sometimes they can be asymptomatic. Indeed, our patient only complained of a mobile, painless swelling, which could have been easily underestimated given the long interval from initial diagnosis, the favourable clinical pathological characteristics of disease (squamous histotype, FIGO stage IB1), and, above all, the unusual and unexpected recurrence presentation. Although the histopathological evaluation represents a more straight forward diagnostic approach, diagnostic imaging techniques are useful tools in order to define the site and extension of disease , and exclude diffuse metastases. However, the differential diagnosis between primary intramuscular tumor and metastasis, which is a very important issue for patient prognosis and clinical management, is not easy: in our case MRI showed an intermediate signal area intensity on T1 and T2-weighted scans, very similar to the muscle tissue but with an important enhancement after the contrast injection. None of the diagnostic tools used documented any signs of the presence of necrosis or haemorrhage. which would have been suggestive of a pattern of rapid growth. In this context, much attention has been focused on the usefulness of FDG-PET not only for staging, but also for the detection of recurrence in cervical carcinoma: in our case FDG-PET findings showed to be critical in order to plan patient management since a diffuse metastatic disease was excluded, and surgical removal of the intercostal muscle recurrence could be planned. Given the very rare occurrence of skeletal muscle metastasis, there are no specific guidelines on the therapeutic options, which include radiotherapy, chemotherapy and surgery according to the clinical setting: indeed, the real benefit of these approaches remains questionable given the very poor prognosis of these patients. As shown in Table 1, in case of a solitary and surgically resectable skeletal muscle metastasis, metastasectomy has been performed, followed by radiotherapy . In our case the choice of a multimodal approach was sustained by i)the young age of the patient and her good performance status; i) the documentation of a single and surgically amenable recurrence; ii) the general consideration of skeletal muscle metastasis as a marker of systemic disease, which would require chemotherapy: in particular the platinum-taxane combination was chosen on the basis of the high response rate documented with this regimen with respect to cisplatin alone ; the choice of using carboplatin instead of cisplatin was motivated by the documentation of a better patient convenience and tolerance together with the encouraging results obtained with carboplatin/paclitaxel regimen in advanced/recurrent pre-irradiated cervical cancer patients . In addition, radiotherapy was planned in order to achieve a better local control of disease, after balancing and discussing with the patient the overall risk of pulmonary fibrosis related to the specific site of irradiation.
In conclusion, we reported a case of a solitary distant skeletal muscle recurrence from early stage cervical cancer after a very long interval from primary diagnosis. Late recurrence (i.e. after a disease-free interval of more than 5 years) in cervical cancer patients is considered a very rare event occurring in approximately 4% of cases with a frequency increasing from 1.8% in stage I, to 5.2% and 8.5% in stage II and III disease, respectively . These figures suggest that cervical cancer patients, especially those bearing stage II-III disease warrant long follow up care, because of the long period of tumor cell dormancy. In particular, muscular pain or weakness, or just a palpable mass in a patient with a history of cervical cancer has always to raise the suspicion of metastatic muscular disease.
This work was financially supported by grants from Associazione Italiana per la Ricerca sul Cancro (A.I.R.C) and I.R.I.S-PCR-OG-ONLUS http://www.iris-og.com.
Written consent was obtained from the patient for publication of the study.
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