|Ahead of print publication
Nodal metastasis of cervix carcinoma- As a probable cause of bone erosion
Sonal Sethi, Vidyasagar Ramalingam, Mukesh Yadav, Sanjay Thulkar
Department of Radiology, IRCH, AIIMS Hospital, New Delhi, India
Department of Radiology, IRCH, AIIMS Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Introduction: Carcinoma of cervix is a common gynaecological malignancy and remains the third most common cancer in developing countries. While nodal metastases are common in cervical cancer, major sites of the less common haematogenous metastases include lung, liver and bones. Bone involvement in cases of carcinoma of cervix is low and the estimates range from 0.8-16 % according to various series.Several patterns of bone involvement are observed in cases of carcinoma of cervix including, (1) direct extension into bone, either from the parametrial extensions of the primary or recurrent pelvic tumor, (2) direct extension into adjacent bone from the pelvic or distant lymph node metastasis (3) regional or systemic haematogenous metastasis to bones.
Aims: To evaluate the pattern of metastases in patients of carcinoma of uterine cervix, with particular emphasis on the pattern of bone involvement on contrast enhanced CT.
Settings and Design: Retrospective study.
Methods and Material: This was a retrospective study, where we reviewed the hospital records and data of patients of cervical cancer who underwent contrast enhanced CT (CECT) of the chest and abdomen over a period of one year between January and December 2016. A total of 100 patients of carcinoma cervix were included. CT images were reviewed by two experienced radiologists. The bony erosion due to pelvic mass or lymphadenopathy was classified as subtle or gross.
Results: Bone involvement was seen in 11 out of 100 cases (11% cases). Among 13 cases direct bone involvement by the pelvic mass/recurrence and metastatic lymph nodes (8/11; 72.7%) was slightly more common than thehematogenous bone metastasis (5/11; 45.4% cases). Among the direct bone involvement direct erosion of the underlying bone by the nodal metastasis (6/8; 75%) was twice more common than the direct bone involvement by the pelvic mass/recurrence(2/8; 25%)
Conclusions: Direct bone involvement by erosion of adjacent bone by nodal metastasis is the most common mechanism of bone involvement in cases of carcinoma of cervix signifying the high propensity of lymph nodal deposits to erode the underlying bone. This finding of direct bone erosion is not seen in any other gynaecological malignancy and should be promptly looked for in all cases of carcinoma of cervix.
Keywords: Bone erosion, cervix carcinoma, lymph nodes, metastases
| > Introduction|| |
Carcinoma of the uterine cervix is a leading cause of morbidity and mortality in women, particularly of the developing nation. The improvements in cervical cancer management techniques including advanced imaging modalities, newer surgical techniques, individualized radiotherapy, and chemotherapy have led to an increase in the survival of patients with cervical cancer. The longer survival has led to a parallel increase in patients presenting with metastases and recurrence. While nodal metastases are common in cervical cancer, the major sites of the less common hematogenous metastases include lung, liver, and bones.
Bone involvement in cases of cervix carcinoma is low, and the estimates range from 0.8% to 16% according to various series. Bone involvement depends on the initial stage of the cancer, with higher stages showing greater degree of involvement and bone involvement is also more evident in cases of recurrent carcinoma cervix compared to patients presenting with primary pelvic tumor., Several patterns of bone involvement are observed in cases of carcinoma of cervix including direct extension into bone, either from the parametrial extensions of the primary or recurrent pelvic tumor, direct extension into adjacent bone from the pelvic or distant lymph node metastasis, and regional or systemic hematogenous metastasis to bones. Although pelvic bone involvement is described in advanced cases of rectal carcinoma, bladder carcinoma, and other gynecological malignancies, the peculiar predilection for nodal metastasis causing underlying bone erosion is described only in cases of cervical cancer. Although there are autopsy and imaging studies emphasizing this predilection, there are no studies based on cross-sectional imaging such as computed tomography (CT). This study was undertaken to evaluate the pattern of metastases in cervix carcinoma patients, with particular emphasis on the pattern of bone involvement on contrast-enhanced CT.
| > Materials and Methods|| |
This is a retrospective analysis of the cervical cancer patients who underwent contrast-enhanced CT of the chest and abdomen over a period of 1 year between January and December 2016. This retrospective study was approved by the Institutional Ethics Committee, and written informed consent was obtained from all patients for performing the CT scan.
CT scan was done on the Siemens Somatom Definition AS 128 slice CT scanner, using standard protocol helical scanning after intravenous injection of 1 ml/kg nonionic iodinated contrast material (Iohexol). All patients also were given positive oral contrast before scanning. Positive rectal contrast was given in patients with suspected rectal involvement.
The CT images were reviewed by two experienced radiologists (5 years and 13 years of experience) who arrived at a consensus opinion. The CT images were evaluated on the Siemens syngo workstation using axial images and coronal, sagittal, or oblique-reformatted images as required for the primary tumor, site of recurrence, pelvic and retroperitoneal lymphadenopathy, site of distant metastasis, and bone involvement (underlying bone erosion from primary/recurrent pelvic mass, underlying bone erosion from retroperitoneal lymphadenopathy, and hematogenous distant bony metastases). The bony erosion due to pelvic mass or lymphadenopathy was classified as subtle or gross. Subtle erosion was defined when the cortical break was evident only on bone whereas gross erosion was defined when the cortical break was evident even on soft tissue. The data related with the age at initial diagnosis, primary presentation/recurrence, FIGO stage, and management of patients with primary tumor/recurrence and metastasis were obtained from hospital records.
| > Results|| |
A total of 100 patients with cervix carcinoma were included in this study. Forty-seven patients (47%) presented with recurrence which was suspected based on either clinical examination or ultrasonography findings during their follow-up visits, and 53 patients (53%) were newly diagnosed with cervix carcinoma and underwent contrast-enhanced CT for investigating the distant metastasis. Bone involvement was observed in 11 patients (11%). Direct bone involvement by the pelvic mass/recurrence and metastatic lymph nodes (8/11; 72.7%) was slightly more common than the hematogenous bone metastasis (5/11; 45.4% cases). Direct erosion of the underlying bone by the nodal metastasis (6/8; 75%) [Figure 1], [Figure 2], [Figure 3], [Figure 4] was twice more common than the direct bone involvement by pelvic mass/recurrence (2/8; 25%) [Figure 5]. One patient showed hematogenous bony metastasis and erosion by pelvic mass [Figure 6], and one patient showed bony erosion by nodal metastasis and hematogenous bony metastasis. [Table 1] and [Table 2] show the distribution of cases among different groups.
|Figure 1: (a and b) Postchemoradiotheraphy case of carcinoma of the cervix shows the left common iliac lymph nodal deposit causing underlying sacral bone erosion|
Click here to view
|Figure 2: (a-d) Case of carcinoma of cervix shows primary mass involving uterus, upper two-third of vagina, parametrium, and extending up to the left lateral pelvic wall. Large deposit in the right external iliac lymph node erodes the underlying pelvic bone. Liver metastasis is seen in segment 6 and diffuse peritoneal spread of carcinoma in the form of peritoneal thickening, deposits in paracolic gutter and ascites is seen|
Click here to view
|Figure 3: (a and b) Postradical hysterectomy case of carcinoma of cervix shows nodal recurrence in the left internal iliac lymph nodes with subtle erosion of underlying iliac bone|
Click here to view
|Figure 4: (a and b) Para-aortic nodal deposits in case of carcinoma of cervix encasing the aorta, infiltrating ipsilateral psoas muscle, and causing subtle underlying vertebral erosion|
Click here to view
|Figure 5: (a and b) Postradical hysterectomy case of carcinoma of the cervix shows vault recurrence infiltrating the rectum and extending up to the lateral pelvic wall eroding right inferior pubic ramus|
Click here to view
|Figure 6: (a-c) Postchemoradiotheraphy case of carcinoma of cervix showing soft tissue in parametrium with extension along mesorectal fascia and presacral space. Subtle erosion of sacral bone is seen beneath the soft tissue in presacral space. Metastatic collapse of L2 vertebrae and mild ascites is also seen|
Click here to view
Sixty-two patients (33 in posttreatment group and 29 in pretreatment group) had nodal recurrence, and the underlying bone erosion was present in 6 patients (9.67%) [Table 3]. Over a period of 1 year, there were 47 patients with cervical cancer recurrence. These patients were treated by radical hysterectomy in case of early involvement and curative radiochemotherapy in case of advanced involvement. Pelvic recurrence was seen in 36 out of 47 patients (76.5%), and nodal recurrence was seen in 33 out of 47 patients (70.2%). Twenty-three patients (44.6%) showed both nodal and pelvic recurrence. Isolated distant metastasis without any nodal or pelvic recurrence was seen only in 1 case that showed lung metastasis as lung nodules in basal segment of the right lobe. Rectovesical and vesicovaginal fistula were each observed in 2 cases, and one case showed ureterovaginal fistula as a complication. [Table 4] shows the distribution of various recurrence sites.
Sixty-two patients had metastasis in pelvic or retroperitoneal lymph nodes, and 27 patients had other distant metastasis. Distant metastasis was present in conjugation with nodal disease in 23 cases, and only 4 patients showed isolated distal metastasis. The remaining 34 cases showed cancer limited to the cervix in pretreatment cases and only isolated pelvic recurrence in posttreatment cases. The lung was the most common site of distant metastasis after lymph nodes. Four cases showed distant metastatic site without any pelvic/retroperitoneal nodal metastasis. Liver metastasis was also seen in only 4 out of 100 cases. Atypical sites of metastasis such as spleen and pleura were also seen in 1 patient each in our study. [Table 5] and [Table 6] show the distribution of various metastasis sites.
| > Discussion|| |
Carcinoma of the cervix is the third most commonly encountered cancer in developing countries. In a study conducted by Matsuyama et al., the incidence of bone metastasis was reported from 4% in stage 1 to 22.9% in stage 4 cervical cancer. The vertebral bodies are by far the most frequently involved bones, followed by the pelvis.,, The incidence of bone metastasis in our study is 11%, and in accordance with the previous studies, vertebral body and pelvic bones were the most commonly involved bones.
In a review of 55 patients with cervical carcinoma-related bone metastases, Blythe et al. divided bone involvement into three main groups as direct extension from the pelvic soft tissue tumor, direct extension from lymphatic focus, and hematogenous spread. It was reported that the most common mechanism of bone involvement was by direct extension of neoplasm from para-aortic nodes into the adjacent vertebral bodies, but the study was limited by the use of radiographs alone as the diagnostic tool. Blythe et al. mentioned their difficulty in determining if pelvic bone involvement occurred from direct extension or direct extension from lymphatics and in distinguishing hematogenous spread to vertebrae from involvement by lymphatic extension.
Another study done by Ratanatharathorn et al. focused on the implication of palliative radiotherapy in case of cervix cancer-related bone metastasis. About 41.5% of patients (17 out of 41) with bone metastasis had bone involvement as the result of direct extension from adjacent soft tissue disease in pelvis, lymph nodal deposits, and lung parenchymal deposits.
In our study, there were 11 cases of bone involvement, and bone involvement was classified into two categories of direct extension and hematogenous bony involvement. In our study, 72.7% of the cases (8 out of 11) showed bone involvement by direct extension, 45.4% of the cases (5 out of 11) had hematogenous bony metastasis, and 18.18% of the cases (2 out of 11) were affected by both mechanisms. Thus, bone involvement by direct extension is a more commonly encountered mechanism than the hematogenous bone involvement. Direct extension by metastatic lymph nodes accounts for 54.45% of the cases (6 out of 11), and this finding correlates with the study conducted by Blythe et al. CT was used as a diagnostic tool so that we could easily differentiate hematogenous involvement of the vertebrae from the direct extension by lymph node deposits.
Six patients out of 62 patients with node deposits (9.67%) were associated with the underlying bone erosion and such high percentage of nodal deposits causing bone erosion is not described in case of any other epithelial malignancy.,,
In accordance with the study of Fulcher et al., our study includes 47 patients with recurrent cervical cancer that showed pelvis and lymph nodes as the two most common recurrence sites. Rectovesical, vesicovaginal, and ureterovaginal fistulas were observed in 5 patients. Incisional site recurrence is a rare site of recurrence in cervix carcinoma,, and there were 4 cases of scar site recurrence [Figure 7].
|Figure 7: (a and b) Two cases of vault recurrence with anterior abdominal wall deposits at the scar site|
Click here to view
In our study, 62 patients (62%) showed lymph node metastasis and 27 patients (27%) had distal metastasis. These percentages are unusually high in comparison to the nodal metastasis incidence of 25% and distant metastasis incidence of 8% documented in literature., These relatively high numbers could be attributed to the fact that preoperative cases of early cervical cancers were not included in the study since chest and abdomen CT was not performed in those cases.
The lungs were the most common distant metastatic sites followed by peritoneal spread of cancer and hematogenous bony metastasis [Figure 8] and [Figure 9]. Cervical cancer can metastasize to unusual places such as breasts, muscles, duodenum, and pleura.
|Figure 8: (a) Case of carcinoma of cervix shows diffuse lung metastasis with multiple vertebral metastasis. Vertebral metastasis at L2 vertebrae shows prominent prevertebral and paravertebral soft tissue encasing the abdominal aorta, (b) Case of carcinoma of cervix shows diffuse lung metastasis, (c) Case of carcinoma of cervix shows vertebral metastasis at L2 vertebrae shows prominent prevertebral and paravertebral soft tissue encasing the abdominal aorta|
Click here to view
|Figure 9: Left inferior pubic ramus metastasis in case of carcinoma of cervix after radical hysterectomy|
Click here to view
The power of the present study is limited by its retrospective design and lack of clinical details such as clinical significance of bone lesions in terms of pain and disability.
| > Conclusion|| |
Bone involvement significantly affects the prognosis of patients with cervix carcinoma, and this involvement occurs by either direct extension from pelvic or nodal soft tissue mass or by hematogenous spread. Direct bone involvement caused by the erosion of adjacent bone by nodal metastasis is the most common mechanism of bone involvement in patients with cervix carcinoma, and this finding signifies the high propensity of lymph nodal deposits to erode the underlying bone in case of cervical cancer.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Fulcher AS, O'Sullivan SG, Segreti EM, Kavanagh BD. Recurrent cervical carcinoma: Typical and atypical manifestations. Radiographics 1999;19:S103-16.
Matsuyama T, Tsukamoto N, Imachi M, Nakano H. Bone metastasis from cervix cancer. Gynecol Oncol 1989;32:72-5.
Ratanatharathorn V, Powers WE, Steverson N, Han I, Ahmad K, Grimm J, et al.
Bone metastasis from cervical cancer. Cancer 1994;73:2372-9.
Höcht S, Mann B, Germer CT, Hammad R, Siegmann A, Wiegel T, et al.
Pelvic sidewall involvement in recurrent rectal cancer. Int J Colorectal Dis 2004;19:108-13.
Tsikouras P, Zervoudis S, Manav B, Tomara E, Iatrakis G, Romanidis C, et al.
Cervical cancer: Screening, diagnosis and staging. J BUON 2016;21:320-5.
Sotto LS, Graham JB, Pickren JW. Postmortem findings in cancer of the cervix. Am J Obstet Gynecol 1960;80:791-4.
Henriksen E. The lymphatic spread of carcinoma of the cervix and of the body of the uterus; a study of 420 necropsies. Am J Obstet Gynecol 1949;58:924-42.
Carlson V, Delclos L, Fletcher GH. Distant metastases in squamous-cell carcinoma of the uterine cervix. Radiology 1967;88:961-6.
Blythe JG, Cohen MH, Buchsbaum HJ, Latourette HB. Bony metastases from carcinoma of cervix. Occurrence, diagnosis, and treatment. Cancer 1975;36:475-84.
Ghosh S, Rao PB. Osseous metastases in gynaecological epithelial malignancies: A Retrospective institutional study and review of literature. J Clin Diagn Res 2015;9:XC10-3.
Hitchins RN, Philip PA, Wignall B, Newlands ES, Begent RH, Rustin GJ, et al.
Bone disease in testicular and extragonadal germ cell tumours. Br J Cancer 1988;58:793-6.
Henriksen E. The dispersion of cancer of the cervix. Radiology 1950;54:812-5.
Torres-Lobaton A, Rueda-Mesias M, Román-Bassaure E, Guadaluperojo-Herrera, Barra-Martínez R. Complications of radical hysterectomy during management of stage Ib and IIa cervix uteri cancer. Experience with 145 patients. Ginecol Obstet Mex 1996;64:265-71.
Sharma DN, Chawla S, Chander S, Gairola M, Thulkar S, Singh MK, et al.
Cervical carcinoma recurring in an abdominal wall incision. Clin Oncol (R Coll Radiol) 2000;12:354-6.
Srivastava K, Singh S, Srivastava M, Srivastava AN. Incisional skin metastasis of a squamous cell cervical carcinoma 3.5 years after radical treatment – A case report. Int J Gynecol Cancer 2005;15:1183-6.
Sakuragi N, Satoh C, Takeda N, Hareyama H, Takeda M, Yamamoto R, et al.
Incidence and distribution pattern of pelvic and paraaortic lymph node metastasis in patients with stages IB, IIA, and IIB cervical carcinoma treated with radical hysterectomy. Cancer 1999;85:1547-54.
Bhandari V, Kausar M, Naik A, Batra M. Unusual metastasis from carcinoma cervix. J Obstet Gynaecol India 2016;66:358-62.
Di Donato V, Palaia I, Perniola G, Polidori N, Burratti M, Besharat A, et al.
Splenic metastasis from cervical cancer: Case report and review of the literature. J Obstet Gynaecol Res 2010;36:887-90.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]