Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Leiomyosarcoma of the Rectum as a Radiation-Induced Second Malignancy after Cervical Cancer Treatment: Case Report with Review of the Literature

Leiomyosarcoma of the Rectum as a Radiation-Induced Second Malignancy after Cervical Cancer... Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 1610653, 8 pages https://doi.org/10.1155/2019/1610653 Case Report Leiomyosarcoma of the Rectum as a Radiation-Induced Second Malignancy after Cervical Cancer Treatment: Case Report with Review of the Literature 1 1 2 1 Dmytro E. Makhmudov , Olena O. Kolesnik, Natalia N. Lagoda, and Maryna O. Volk Oncocoloproctology Department, National Cancer Institute, Lomonosova str. 33/43, Kyiv 03022, Ukraine Department of Pathomorphology, National Cancer Institute, Lomonosova str. 33/43, Kyiv 03022, Ukraine Correspondence should be addressed to Dmytro E. Makhmudov; dmahmudoff@gmail.com Received 13 August 2019; Accepted 14 November 2019; Published 10 December 2019 Academic Editor: Peter F. Lenehan Copyright © 2019 Dmytro E. Makhmudov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Incidence of cervical cancer among women of reproductive age still remains significantly high. In regard to prognostic features and risk factors, the standard treatment for most types of cervical cancer represents a combination of surgical treatment and radiation therapy, such as external beam radiation therapy and brachytherapy. Despite significant advances of long-term oncological outcomes, radiation-induced secondary malignancies among cervical cancer survivors are still an issue. Current case report describes an incredibly rare case of radiation-induced leiomyosarcoma of the rectum, which occurred 32 years after cervical cancer treatment. Case Presentation. A 62-year-old female had a past medical history of FIGO stage IIB cervical cancer (squamous cell carcinoma pT2bN0M0). In 1987, she underwent radical hysterectomy with bilateral iliac lymph node dissection, followed by adjuvant radiation therapy—70 Gy external beam pelvic irradiation followed by 30.5 Gy of brachytherapy. Thirty-two years later, she presented with signs of rectal bleeding. Regarding past medical history, radiologic, endoscopic, and pathologic data, the patient was initially diagnosed with a malignant nonepithelial lower rectal tumor of the unknown origin and staged as mrT3a mrN0 cM0. Total mesorectal excision with complete mesocolic excision and central vascular ligation (CME/CVL) carried by an open approach was carried out. In an attempt to identify the tissue of origin, an immunohistochemistry assay had been performed. Tumor cells showed a high rate of mitotic activity with a 45% rate of Ki-67 expression, positive reaction for desmin, and SMA in all samples. Negative reaction for CD117 and S100 was observed. As a conclusion, the immunophenotype was identified as a grade 3 leiomyosarcoma (ISD-code 8890/3). Conclusions. We suggest that up to date, radical surgery with curative intent, as it was performed in our study, is the most evidence-based treatment option for patients with radiation-induced sarcomas of the rectum. 1. Background their scattered features, prognostic factors and optimal treatment strategy for primary colorectal sarcomas remain indeterminate. However, pooled data from a majority of Primary colorectal sarcomas are an extremely rare group of malignant mesenchymal tumors. They represent up to 0.1% recently published case series suggest that primary colorec- tal sarcomas are characterized by both rapid progression of all primary diagnosed colorectal malignancies [1]. Leio- and very poor oncological outcomes with a median of sur- myosarcomas appear to be the most common histological subtype of primary colorectal sarcomas with incidence up vival ranging from 30 to 53 months and a local recurrence rate of up to 85% [3–6]. Overall five-year survival rate of to 90%. More rare of their subtypes are liposarcomas, patients with primary colorectal sarcomas is significantly fibrous histiocytomas, and desmoplastic small cell tumors lower comparing to those with colorectal cancer—43% [2]. Regarding the small number of documented cases and 2 Case Reports in Oncological Medicine (a) (b) (c) Figure 1: Radiologic data from a high-resolution pelvic MRI. Tumor of the lower rectum (1) situated on the anterior wall was observed on sagittal (a) and axial T2-weighted scans (b) with signs of mesorectal invasion (blue arrowheads) ranging up to 3 mm and no radiologic features of lymph node metastases (3). Vaginal stump and rectovaginal sept (2) had a significantly low intensity MR signal due to their fibrotic transformation. On a series of diffusion-weighted images (c), a significant delay of diffusion together with intense signaling on high b-factors was observed at the level of a tumor (blue arrowheads). and 52%, respectively [7]. Tumor grade of primary colorec- identified. No radiological signs of either mesorectal fascia tal sarcomas is the most important prognostic factor for involvement or extramural vascular invasion (mrCRM and overall five-year survival—38% for high grade and 61% for mrEMVI ) had been observed (see Figures 1(a) and 1(b)). Vis- low grade [8]. Besides, inappropriate staging algorithm and ible mesorectal lymph nodes had homogenous MR signal, wide use of local excision as a surgical option for primary smooth external margins, and a regular size, thus showing no treatment results in high rates of R1 and R2 resections with radiologic signs of lymph node involvement (mrN ). It was a local recurrence rate of 12.7%. Nevertheless, a number of noticeable that the stump of the vagina and rectovaginal sept authors suggest that curative surgery should be the main had prominent signs of fibrosis regarding a highly intensive treatment option because data regarding chemotherapy MR signal on T2-weighted images. Malignant tumor features and radiation therapy is either lacking or it is controversial were also observed on a series of diffusion-weighted images [9, 10]. Colorectal sarcomas as a radiation-induced second (see Figure 1(c)). malignancy after cervical cancer treatment, on contrary to A CT scan with intravenous enhancement showed no primary ones, are an exceptionally rare entity. Up to date, signs of neither distant metastases neither thoracic or intra- only five cases had been described in the literature [11–15]. abdominal lymphadenopathy. Upper GI endoscopy and lab- In our current paper, we provide data on the sixth case of oratory data of standard blood, serum, and urine counts similar malignancy. revealed no signs of pathology. 2. Case Presentation 3. Surgical Treatment A 62-year-old female had a past medical history of FIGO stage IIB cervical cancer (squamous cell carcinoma Regarding past medical history, radiologic, endoscopic, and pT2bN0M0). In 1987, she underwent radical hysterectomy pathologic data, the patient was initially diagnosed with a with bilateral iliac lymph node dissection, followed by malignant nonepithelial lower rectal tumor of the unknown adjuvant radiation therapy—70 Gy external beam pelvic origin and staged as mrT3a mrN0 cM0. Being aware of pri- irradiation followed by 30.5 Gy of brachytherapy. Thirty- mary colorectal sarcomas, their recurrence and progression two years later, she presented with signs of rectal bleeding. patterns and a threatening rate of R1 and R2 resections, an Digital rectal examination revealed a solid exophytic institutional multidisciplinary board suggested curative sur- tumor on 5 cm above the anal verge. During rigid procto- gery as a primary treatment option. Total mesorectal excision sigmoidoscopy, a 3 cm anterior wall rectal tumor with (TME) with complete mesocolic excision and central vascu- irregular margins and swollen mucosa was observed. Addi- lar ligation (CME/CVL) carried by an open approach was tional flexible colonoscopy showed no signs of synchronous selected as proper extent of surgery. Standardized surgical colorectal neoplasms. Snare biopsy result showed an undif- technique in this case included complete left flexure mobili- ferentiated malignant nonepithelial tumor of unidentified zation, ligation of the inferior mesenteric artery at its origin histological origin. An attempt of immunohistochemistry near the aorta and inferior mesenteric vein just below the assay was undertaken unsuccessfully due to an insufficient pancreatic tail with consecutive total mesorectal excision up amount of tissue. to the level of the pelvic diaphragm (see Figure 2). Accurate Consecutively, a pelvic MRI with a 1.5 Tl Philips Intera TME procedure had been exacerbated by severe fibrotic machine had been performed for local staging. MERCURY changes of surrounding pelvic tissues due to postoperative protocol for high resolution imaging was applied. changes after iliac lymphadenectomy for cervical cancer On a series of sagittal and axial MR scans, a lower rectal and radiation-induced fibrosis as well. Regarding the signifi- tumor was observed on 4 cm above the anorectal junction with cant fibrotic transformation of the anterior rectal wall with maximal extent of 30 mm in the greatest dimension. Mesorec- adjacent tissues, an intraoperative decision was made to tal infiltration with maximal depth of 3 mm (mrT ) was also avoid reconstruction aware of an estimated high risk of 3b Case Reports in Oncological Medicine 3 4. Pathologic Findings Macroscopically, the tumor was represented an exophytic homogenous lesion 45 × 25 mm with irregular margins and ulcerated surface covered with clots of fibrin. The tumor originated from the muscular layer of the rectum with con- comitant mucosal invasion. Twelve regional lymph nodes were additionally examined. Initial histological appearance revealed a mixture of chaotic cellular and fibrotic vegeta- tions. Among them, a subgroup of heterogeneous polykar- yocytes with significant nuclear polymorphism (so called “monster cells”) was identified (see Figure 5). Those and other morphological features corresponded to a malignant low-grade mesenchymal tumor. All examined lymph nodes had no signs of metastases. In an attempt to identify the tissue of origin for a current tumor, an immunohistochemistry assay had been carried out. A panel of Ki-67, CD117, S100, smooth muscle actin (SMA), and desmin was used to conduct a differential diag- nosis between leiomyosarcoma and gastrointestinal stromal tumor. Tumor cells showed a high rate of mitotic activity with a 45% rate of Ki-67 expression (see Figure 6). There was a positive reaction for desmin and SMA in all samples (see Figures 7 and 8). On contrary, all samples had negative Figure 2: Resected gross specimen. 1: stump of the inferior reaction for CD117 and S100 (see Figures 9 and 10). As a mesenteric artery, 2: stump of the inferior mesenteric vein, 3: conclusion, the observed immunophenotype was identified preserved peritoneal window, 4: level of the peritoneal reflection, as a grade 3 leiomyosarcoma (ISD-code 8890/3). and 5: mesorectum. anastomotic leakage. Closure of the pelvic peritoneum was 5. Discussion avoided as well. On postoperative day 5, the patient developed such clin- In the current paper, we present the sixth case of radiation- ical signs as nausea, vomiting, and loss of flatus and stool. induced leiomyosarcoma of the rectum which developed 32 Computed tomography of the chest, abdomen, and pelvis years after completion of cervical cancer treatment. revealed multiple “levels” of gas and liquid throughout the Throughout the last decades, significant success was small intestine with a breakdown of peroral contrast at the achieved in the treatment of patients with pelvic malignan- level of distal ileal loop, which was situated at the cavity of cies, especially those who require either adjuvant or neoadju- minor pelvis, adherent to the stumps of both the rectum vant radiation therapy. As a consequence of overall survival and the vagina (see Figure 3). At that level, a noticeable defor- improvement, the problem of metachronous secondary mation of the intestinal loop with difference of luminal diam- malignancies among those patients who were exposed to eters was observed. On contrary, the lumen of a large radiation had arisen. According to the data of the National intestine was collapsed. Cancer Institute of USA, over 40% of all patients diagnosed By taking in regard both clinical and radiologic find- with primary malignancy will have to undergo radiation ings, the patient was diagnosed with postoperative ileus therapy [16]. Most of primary malignancies which require and an immediate reoperation had been carried out. Dur- radiation therapy as a treatment standard are breast, pros- ing abdominal examination, dilated intestinal loops with tate, cervical, rectal, and urinary bladder cancer. Among block of passage at the level of the pelvic diaphragm were long-term cancer survivors exposed to radiation, 16% are identified (see Figure 4). An adherent bowel wall was fixed at risk of developing a secondary malignancy. Recent data between vaginal and rectal stumps as it was previously from a SEER database suggests that 6–9.9% of all patients described on a series of CT scans. By the end of abdomi- who underwent radiation therapy for prostate cancer are at nal and pelvic exploration, no additional pathological find- a 34% risk of developing secondary lung, rectal, or urinary ings were observed. After detachment of adhesions, the bladder cancer. Majority of those patients develop secondary strangulated bowel was delivered back in the abdominal malignancies mostly after 10 years from treatment discon- cavity. Closure of the pelvis was performed with mobilized tinuation [17, 18]. body of the urinary bladder and remnant flaps of pelvic Cervical cancer remains one of the leading cause of peritoneum. Postoperative period was uneventful within cancer-related morbidity and mortality among females [19]. 30 days. The patient was safely discharged on postopera- It is known that only surgical treatment can be appropriate tive day 14 after initial surgery. At one year of follow- only in a relatively small subgroup of patients, particularly up, the patient is alive and has no radiological signs of among those who were initially diagnosed with FIGO stage neither local nor distant recurrence. IA1 (T1a1 by TNM) or less, i.e., with a depth of stromal 4 Case Reports in Oncological Medicine (a) (b) th Figure 3: Patient’s CT scans on the 6 postoperative day. Multiple intestinal “levels” of gas and fluid throughout the abdominal cavity were observed ((a), red arrowheads). Part of the distal intestinal loop with difference in lumen diameters was situated at the level of the pelvic floor ((b), yellow arrowheads) and was adherent to both rectal and vaginal stumps. Figure 6: Poorly differentiated malignant mesenchymal tumor. Immunohistochemistry assay with Ki-67 antibodies. Figure 4: Intraoperative photo during reoperation. Dilated intestinal loops up to the level of distal ileum (1) are observed. The loop of a strangulated bowel (2) was adherent to the stump of the rectum and vagina deep inside the pelvic cavity. Figure 7: Poorly differentiated malignant mesenchymal tumor. Immunohistochemistry assay with desmin antibodies. Positive reaction in tumor cells observed. invasion up to 3 mm and lateral spread up to 7 mm [20]. Recent NCCN guidelines suggest adjuvant radiation therapy for FIGO stage IA1 patients with a number of adverse risk features found at pathological examination, such as positive lymph nodes, parametrium invasion, or positive resection margins [21]. A standard approach for cervical cancer radia- tion therapy includes combination of external beam radia- Figure 5: Poorly differentiated malignant mesenchymal tumor. tion therapy and brachytherapy. Overall radiation dosage Multiple sites of cellular and nuclear polymorphism are observed. depends on the range of primary tumor spread—in cases of Hematoxylin-eosin staining, ×100. tumors below 40 mm in maximum dimension, the overall dosage consists of 80 Gy and ≥85 Gy if above 40 mm. Case Reports in Oncological Medicine 5 Figure 8: Poorly differentiated malignant mesenchymal tumor. Figure 10: Poorly differentiated malignant mesenchymal tumor. Immunohistochemistry assay with SMA antibodies. Positive Immunohistochemistry assay with S100 antibodies. Negative reaction in tumor cells observed. reaction in tumor cells observed. secondary malignancy development was the age under 30 years at primary diagnosis of cervical cancer. Urinary bladder (4.5), vagina (2.7), stomach (2.1), and hematopoietic tissue (2.5) had the highest relative risk for secondary malignancy. It was noticeable that the rectum had the lowest relative risk among other pelvic organs (1.8). Other data from a study of Samerdokiene et al. suggest that secondary radiation- induced malignancies occur in 5.3% of cervical patients after a combination of external beam and brachytherapy. Among them, rectal malignancies consisted only 8.6% [23]. A popu- lation study of 37,757 patients based on a data from SEER database demonstrated a 2.6-fold increase in a number of secondary malignancies among those cervical cancer patients Figure 9: Poorly differentiated malignant mesenchymal tumor. who underwent pelvic radiation therapy comparing to sur- Immunohistochemistry assay with CD117 antibodies. Negative gery alone [24]. Nevertheless, the authors acknowledged that reaction in tumor cells observed. metachronous bronchopulmonary, esophageal, and oropha- ryngeal cancer were mostly caused by continuous smoking In cases of cervical cancer, the radiation field includes and vaginal, vulval, and anal canal cancer—by HPV infection parametrium, sacrouterine ligaments, 3 cm of upper third rather than by previous radiation exposure. Similar retro- of the vagina below the tumor, and presacral, obturator, spective population-based data concerning a consistent pat- external, and internal iliac lymph nodes. By taking in regard tern of an increased secondary malignancy rate among all the anatomical relations of the cervix, it becomes clear that cervical cancer survivors was obtained from the Netherlands the most critical radiation sites are represented by the vagina, and Taiwan [25, 26]. Even though all secondary colon, rectal, the rectum, and the urinary bladder. In comparison, bony and anal malignancies in those studies were united in one pelvis structures receive significantly lesser radiation dosages. subgroup, their relative risk ratio still remained one of the A successful combination of curative surgery and highly lowest. A study by Ohno et al., based on a pooled data from precise modalities of radiation therapy in either adjuvant or 2167 patients after a combination of external beam and neoadjuvant regimens had given a unique opportunity to brachytherapy for cervical cancer, reports a 9.7% rate of sec- improve cervical cancer patient’s overall and disease-free sur- ondary radiation-induced malignancies with 19% of them vival rates like never before. Hence, by dropping out of a can- related to adjacent irradiated organs [27]. Soft tissue and cer recurrence group, those patients consequently enter bone sarcomas (22.0), leukemias (3.1), and urinary bladder another one—a risk group of developing a secondary malig- cancer (2.2) had the greatest relative risk rates. On the other nancy. The first population-based study which highlighted hand, rectal cancer, hepatocellular carcinoma, and gastric a relevance between previous exposure to pelvic irradiation cancer (1.0, 1.2 and, respectively) possessed the lowest rela- and a risk of developing a second malignancy was presented tive risk rates. Lim et al. came up with a data of 72,805 inva- by Boice et al., in 1984 [22]. The study included more than sive cervical cancer patients after pelvic irradiation within a 95,000 patients after pelvic radiation therapy for cervical study period of 7.34 years [28]. A 3.68% rate (2678 cases) cancer within a 30-year study period. This population was of secondary radiation-induced malignancies with similar compared with more than 99,000 patients who underwent relative risk patterns—vagina (9.36), soft tissues and bones only curative surgery. Throughout the study period, 3324 (2.7), vulva (2.58), and anus and anal canal (2.42)—was (3.5%) secondary radiation-induced malignancies had been observed. It is noticeable that among the 35 sites of secondary observed, of which 1622 (1.7%) were located at the organs malignancy occurrence, rectal cancer had the lowest relative covered by the irradiation field. The main risk factor of risk of 0.74. Correlation between previously treated cervical 6 Case Reports in Oncological Medicine Table 1: Pooled data of all identified case reports of radiation-induced leiomyosarcoma of the rectum after pelvic radiation therapy for cervical cancer. Time to diagnosis Year of Patient’s age Overall irradiation Radiation Selected treatment Authors of a secondary publication at diagnosis dosage (Gy) modality strategy malignancy (years) 40 Gy Intra-abdominal Drumea et al. [11] 1993 62 70 17 1 2 resection of the rectum EBRT +30 Gy BT Caporale et al. [12] 2003 N/A N/A N/A N/A N/A Intra-abdominal Basu et al. [13] 2012 79 N/A N/A 26 resection of the rectum Sigmostomy+ Garcia-Ortega 50 Gy 2018 58 85 8 chemotherapy+pelvic et al. [14] EBRT+35 Gy BT exenteration+vulvectomy Jayakumar et al. [15] 2015 58 N/A N/A 15 Local excision 70 Gy EBRT+ Current case report 2019 62 100.5 32 ТМЕ+CME/CVL 30.5 Gy BT 1 2 EBRT: external beam radiation therapy. BT: brachytherapy. cancer secondary colorectal cancer had been recently only in 12% of radiation-induced sarcomas. However, there highlighted in a paper of Rodriguez et al. [29]. After 35 years was absolutely no data regarding a radiation-induced leio- of follow-up, an estimated risk of colon cancer was 2.5% in a myosarcoma after previous pelvic radiation therapy with surgery alone group and 6.5% in a radiation therapy group. intra-abdominal or either intrapelvic localization. For rectal cancer, the difference was more significant—0.8% Remarkably, but up to date, there were only 5 published and 3.7%, respectively. Regression analysis survival model case reports of a radiation-induced leiomyosarcoma of the demonstrated a significant increase of relative risk for colon rectum in a patient after previous radiation therapy for cervi- cancer development after 8 years and rectal cancer—after cal cancer (see Table 1). On the contrary, one of the largest recent studies by Thiels et al. evaluates a series of 433 primary 15 years of follow-up. The authors suggest that 8 years should be a cutoff edge for colorectal cancer screening among cervi- colorectal sarcomas discovered within a 14-year observation cal cancer survivors. period [8]. Among the 29.3% of patients with the rectum as First studies about the influence of ionizing radiation on a primary tumor site, only 57.5% had leiomyosarcomas. the development of malignancies were provided after a Although radiation-induced leiomyosarcomas of the rectum appear to be an extremely rare type of secondary nuclear attack in Japan at 1945. Three main issues had been discovered then: tissues with higher proliferative index (i.e., malignancies, there is an emerging data suggesting an intrin- epithelial and hematopoietic) are mostly affected; very small sically different sequence of molecular events responsible for number of radiation-induced sarcomas and a ratio of 8%/1 their development and occurrence comparing to primary Gray, which is a distribution of those who shall develop a sarcomas [14]. Gonin-Laurent et al. recognize a mutation of ТР53 and RB1 genes as a key molecular event in the develop- malignancy among one hundred people exposed to an irradi- ation dosage of 1 Gy [30]. Mechanisms and conditions for ment of radiation-induced sarcomas. Consecutive mutation radiation sarcoma development were firstly described by of a TP53 gene was identified in 58% of radiation-induced Cahan et al. in 1948 [31]. It was noticed that the occurrence sarcomas and was related to deletion of other oncogenes in of pathologically confirmed secondary sarcomas is related 52% [34, 35]. It was also mentioned that mutation of a TP53 gene led to inactivation of RB1, which showed no signs to an irradiation field previously exposed to a dosage of at least 50 Gy. However, the only uncertainty was timing of of genetic alterations [35]. Hyperexpression of р53 is recog- occurrence which could range from months to decades. nized as a specific pathogenic route for radiation-induced Despite meeting all of Cahan’s criteria, radiation-induced sarcoma development as well. Taubert et al. identified a р53 sarcomas in cervical cancer patients after pelvic radiation mutation in 9 out of 11 radiation-induced sarcoma cases [36]. Finally, a study of Nakanishi et al. revealed a р53 muta- therapy are a very rare entity. Among all primary diagnosed soft tissue sarcomas, a range of 0.03% to 5.5% could be con- tion pattern in a series of 14 secondary radiation-induced soft sidered as radiation induced [32, 33]. tissue sarcomas in patients who previously underwent pelvic According to the largest published series of Cha et al., radiation therapy for cervical cancer [37]. Real-time poly- only 125 (2.5%) out of 4884 primary soft tissue sarcomas sat- merase chain reaction detected polymorphism of р53 gene with an 88% rate of mutations in exons 5, 7, 8, 12, and 18. isfied Cahan’s criteria and were considered as radiation induced [32]. Vast majority of those patients previously However, concomitant changes in the primary structure of underwent radiation therapy for breast cancer (29%), lym- a p53 protein were observed only in 31%. The authors con- phomas (16%), and prostate cancer (14%) with thoracic cav- clude that such a biological mislead might be a reason for a ity, thoracic wall, extremities, head and neck as a tumor site. long latency period between radiation exposure and clinical manifestation of secondary soft tissue sarcomas. Pathological features of leiomyosarcomas were identified Case Reports in Oncological Medicine 7 [9] C. D. Randleman, B. G. Wolff, R. R. Dozois, R. J. Spencer, L. H. 6. Conclusions Weiland, and D. M. Ilstrup, “Leiomyosarcoma of the rectum Among all radiation-induced malignancies affecting long- and anus,” International Journal of Colorectal Disease, vol. 4, term cervical cancer survivors, soft tissue sarcomas occur no. 2, pp. 91–96, 1989. quite frequently. However, radiation-induced leiomyosar- [10] B. D. Minsky, A. M. Cohen, S. I. Hajdu, and D. Nori, “Sphinc- coma of the rectum represents a remarkably rare case. ter preservation in rectal sarcoma,” Diseases of the Colon and Although primary colorectal sarcomas represent a very Rectum, vol. 33, no. 4, pp. 319–322, 1990. small subgroup of malignant mesenchymal tumors, the [11] K. Drumea, E. Sabo, E. Zuckerman, and J. E. Naschitz, “Leio- data regarding its proper treatment is lacking. On contrary myosarcoma of the colon in the aftermath of pelvic irradiation for endometrial carcinoma,” The American Journal of Gastro- to primary ones, radiation-induced sarcomas possess a enterology, vol. 88, article 1302, 1993. number of unique molecular features which make them [12] A. Caporale, F. Angelico, M. U. Cosenza et al., “A late compli- biologically different. We suggest that up to date, radical cation of pelvic radiotherapy: leiomyosarcoma of the rectum. surgery with curative intent, as it was performed in our Report of a case and review of the literature,” Hepatogastroen- study, is the most evidence-based treatment option for terology, vol. 50, no. 54, pp. 1933–1936, 2003. patients with radiation-induced sarcomas of the rectum. [13] I. Basu and P. Lemonas, “Leiomyosarcoma of the rectum fol- Fibrotic changes in the pelvis as a consequence of previous lowing pelvic irradiation: a difficult histological diagnosis,” external beam and brachytherapy may significantly jeopar- Annals of the Royal College of Surgeons of England, vol. 94, dise the completion of a TME procedure. That is why a no. 1, pp. e44–e45, 2012. two-step surgical strategy with delayed reconstruction [14] D. Y. Garcia-Ortega, N. Reyes-Garcia, H. Martinez-Said, C. H. should be taken in regard. S. Caro-Sanchez, and M. Cuellar-Hubbe, “Radiation-induced leiomyosarcoma of the rectum after cervical cancer treat- Consent ment,” Revista de Gastroenterología de México, vol. 83, no. 4, pp. 465–467, 2018. Before the publication of the present clinical case, the patient [15] R. Jayakumar, P. P. Basu, T. Huang, and C. A. Axiotis, “Post- filled out a written informed consent approving the use of her irradiation leiomyosarcoma of rectum presenting as a polyp: personal data in scientific purposes. case report and review of the literature,” International Journal of Surgical Pathology, vol. 24, no. 2, pp. 163–169, 2015. [16] L. B. Travis, C. S. Rabkin, L. M. Brown et al., “Cancer sur- Conflicts of Interest vivorship—genetic susceptibility and second primary can- cers: research strategies and recommendations,” JNCI: The authors declare that they have no conflicts of interest. Journal of the National Cancer Institute, vol. 98, no. 1, pp. 15–25, 2006. References [17] D. J. Brenner, R. E. Curtis, E. J. Hall, and E. Ron, “Second malig- nancies in prostate carcinoma patients after radiotherapy com- [1] M. Cuffy, F. Abir, and W. E. Longo, “Management of less com- pared with surgery,” Cancer, vol. 88, no. 2, pp. 398–406, 2000. mon tumors of the colon, rectum, and anus,” Clinical Colorec- [18] K. Moon, G. J. Stukenborg, J. Keim, and D. Theodorescu, tal Cancer, vol. 5, no. 5, pp. 327–337, 2006. “Cancer incidence after localized therapy for prostate cancer,” [2] S. Meijer, T. Peretz, J. J. Gaynor, C. Tan, S. I. Hajdu, and M. F. Cancer, vol. 107, no. 5, pp. 991–998, 2006. Brennan, “Primary colorectal sarcoma. A retrospective review [19] L. A. Torre, F. Bray, R. L. Siegel, J. Ferlay, J. Lortet-Tieulent, and prognostic factor study of 50 consecutive patients,” and A. Jemal, “Global cancer statistics, 2012,” CA: a Cancer Archives of Surgery, vol. 125, no. 9, pp. 1163–1168, 1990. Journal for Clinicians, vol. 65, no. 2, pp. 87–108, 2015. [3] K. C. Conlon, E. S. Casper, and M. F. Brennan, “Primary gas- [20] C. Marth, F. Landoni, S. Mahner et al., “Cervical cancer: ESMO trointestinal sarcomas: analysis of prognostic variables,” clinical practice guidelines for diagnosis, treatment and follow- Annals of Surgical Oncology, vol. 2, no. 1, pp. 26–31, 1995. up,” Annals of Oncology, vol. 28, supplement 4, pp. iv72–iv83, [4] C. L. Chou, S. C. Chang, T. C. Lin et al., “Clinical analysis and surgical results of primary colorectal sarcoma,” The Journal of [21] National Comprehensive Cancer Network, “Cervical cancer,” Society of Colon and Rectal Surgeons (Taiwan), vol. 21, pp. 161–168, 2010. 2019, https://www.nccn.org/professionals/physician_gls/pdf/ cervical.pdf. [5] P. Luna-Pérez, D. F. Rodríguez, L. Luján et al., “Colorectal sar- coma: analysis of failure patterns,” Journal of Surgical Oncol- [22] J. D. Boice Jr., N. E. Day, A. Andersen et al., “Second cancers ogy, vol. 69, no. 1, pp. 36–40, 1998. following radiation treatment for cervical cancer: an interna- tional collaboration among cancer registries,” JNCI: Journal [6] J. Yang, “Primary leiomyosarcoma in the colon: A case report,” of the National Cancer Institute, vol. 74, no. 5, pp. 955–975, Medicine (Baltimore), vol. 97, no. 7, 2018. [7] C. R. Cooper, B. F. Scully, and S. Lee-Kong, “Colorectal sar- coma: more than a gastrointestinal stromal tumor,” Transla- [23] V. Samerdokiene, K. P. Valuckas, E. Janulionis, V. Atkocius, and M. J. Rivard, “Second primary malignancies after radio- tional Gastroenterology and Hepatology, vol. 3, pp. 42–42, 2018. therapy including HDR Cf brachytherapy for cervical can- cer,” Brachytherapy, vol. 14, no. 6, pp. 898–904, 2015. [8] C. A. Thiels, J. R. Bergquist, A. C. Krajewski et al., “Outcomes of primary colorectal sarcoma: a National Cancer Data Base [24] R. E. Curtis, D. Michal Freedman, E. Ron et al., “New malig- (NCDB) review,” Journal of Gastrointestinal Surgery, vol. 21, nancies among cancer survivors: SEER cancer registries, no. 3, pp. 560–568, 2017. 1973–2000,” National Cancer Institute, 2006. 8 Case Reports in Oncological Medicine [25] M. Arnold, L. Liu, G. G. Kenter, C. L. Creutzberg, J. W. Coe- bergh, and I. Soerjomataram, “Second primary cancers in sur- vivors of cervical cancer in the Netherlands: implications for prevention and surveillance,” Radiotherapy and Oncology, vol. 111, no. 3, pp. 374–381, 2014. [26] C. J. Teng, L. K. Huon, Y. W. Hu et al., “Secondary primary malignancy risk in patients with cervical cancer in Taiwan: a nationwide population-based study,” Medicine, vol. 94, p. 43, [27] T. Ohno, S. Kato, S. Sato et al., “Long-term survival and risk of second cancers after radiotherapy for cervical cancer,” Interna- tional Journal of Radiation Oncology·Biology·Physics, vol. 69, no. 3, pp. 740–745, 2007. [28] M. C. Lim, Y. J. Won, J. Lim et al., “Second primary cancer after diagnosis and treatment of cervical cancer,” Cancer Research and Treatment, vol. 48, no. 2, pp. 641–649, 2016. [29] A. M. Rodriguez, Y.-F. Kuo, and J. S. Goodwin, “Risk of colo- rectal cancer among long-term cervical cancer survivors,” Medical Oncology, vol. 31, no. 5, p. 943, 2014. [30] E. J. Hall and C. S. Wuu, “Radiation-induced second cancers: the impact of 3D-CRT and IMRT,” International Journal of Radiation Oncology, Biology, Physics, vol. 56, no. 1, pp. 83– 88, 2003. [31] W. Cahan, H. Woodward, N. Higinbotham, F. W. Stewart, and B. L. Coley, “Sarcoma in irradiated bone. report of eleven cases,” Cancer, vol. 1, no. 1, pp. 3–29, 1948. [32] C. Cha, C. R. Antonescu, M. L. Quan, S. Maru, and M. F. Bren- nan, “Long-term results with resection of radiation-induced soft tissue sarcomas,” Annals of Surgery, vol. 239, no. 6, pp. 903–910, 2004. [33] A. Italiano, S. Bringer, J. Y. Blay et al., “Patterns of care and outcome radiation-induced soft tissue sarcomas,” Interna- tional Journal of Radiation Oncology·Biology·Physics, vol. 103, no. 2, pp. 449–452, 2019. [34] N. Gonin-Laurent, N. S. Hadj-Hamou, N. Vogt et al., “RB1 and TP53 pathways in radiation-induced sarcomas,” Oncogene, vol. 26, no. 41, pp. 6106–6112, 2007. [35] N. Gonin-Laurent, A. Gibaud, M. Huygue et al., “Specific TP53 mutation pattern in radiation-induced sarcomas,” Carcinogen- esis, vol. 27, no. 6, pp. 1266–1272, 2006. [36] H. Taubert, A. Meye, M. Bache et al., “p 53 status in radiation- induced soft-tissue sarcomas,” Strahlentherapie und Onkolo- gie, vol. 174, no. 8, pp. 427–430, 1998. [37] H. Nakanishi, Y. Tomita, A. Myoui et al., “Mutation of the p 53 gene in postradiation sarcoma,” Laboratory Investigation, vol. 78, no. 6, pp. 727–733, 1998. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

Leiomyosarcoma of the Rectum as a Radiation-Induced Second Malignancy after Cervical Cancer Treatment: Case Report with Review of the Literature

Loading next page...
 
/lp/hindawi-publishing-corporation/leiomyosarcoma-of-the-rectum-as-a-radiation-induced-second-malignancy-msdpROjcFE
Publisher
Hindawi Publishing Corporation
Copyright
Copyright © 2019 Dmytro E. Makhmudov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN
2090-6706
eISSN
2090-6714
DOI
10.1155/2019/1610653
Publisher site
See Article on Publisher Site

Abstract

Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 1610653, 8 pages https://doi.org/10.1155/2019/1610653 Case Report Leiomyosarcoma of the Rectum as a Radiation-Induced Second Malignancy after Cervical Cancer Treatment: Case Report with Review of the Literature 1 1 2 1 Dmytro E. Makhmudov , Olena O. Kolesnik, Natalia N. Lagoda, and Maryna O. Volk Oncocoloproctology Department, National Cancer Institute, Lomonosova str. 33/43, Kyiv 03022, Ukraine Department of Pathomorphology, National Cancer Institute, Lomonosova str. 33/43, Kyiv 03022, Ukraine Correspondence should be addressed to Dmytro E. Makhmudov; dmahmudoff@gmail.com Received 13 August 2019; Accepted 14 November 2019; Published 10 December 2019 Academic Editor: Peter F. Lenehan Copyright © 2019 Dmytro E. Makhmudov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Incidence of cervical cancer among women of reproductive age still remains significantly high. In regard to prognostic features and risk factors, the standard treatment for most types of cervical cancer represents a combination of surgical treatment and radiation therapy, such as external beam radiation therapy and brachytherapy. Despite significant advances of long-term oncological outcomes, radiation-induced secondary malignancies among cervical cancer survivors are still an issue. Current case report describes an incredibly rare case of radiation-induced leiomyosarcoma of the rectum, which occurred 32 years after cervical cancer treatment. Case Presentation. A 62-year-old female had a past medical history of FIGO stage IIB cervical cancer (squamous cell carcinoma pT2bN0M0). In 1987, she underwent radical hysterectomy with bilateral iliac lymph node dissection, followed by adjuvant radiation therapy—70 Gy external beam pelvic irradiation followed by 30.5 Gy of brachytherapy. Thirty-two years later, she presented with signs of rectal bleeding. Regarding past medical history, radiologic, endoscopic, and pathologic data, the patient was initially diagnosed with a malignant nonepithelial lower rectal tumor of the unknown origin and staged as mrT3a mrN0 cM0. Total mesorectal excision with complete mesocolic excision and central vascular ligation (CME/CVL) carried by an open approach was carried out. In an attempt to identify the tissue of origin, an immunohistochemistry assay had been performed. Tumor cells showed a high rate of mitotic activity with a 45% rate of Ki-67 expression, positive reaction for desmin, and SMA in all samples. Negative reaction for CD117 and S100 was observed. As a conclusion, the immunophenotype was identified as a grade 3 leiomyosarcoma (ISD-code 8890/3). Conclusions. We suggest that up to date, radical surgery with curative intent, as it was performed in our study, is the most evidence-based treatment option for patients with radiation-induced sarcomas of the rectum. 1. Background their scattered features, prognostic factors and optimal treatment strategy for primary colorectal sarcomas remain indeterminate. However, pooled data from a majority of Primary colorectal sarcomas are an extremely rare group of malignant mesenchymal tumors. They represent up to 0.1% recently published case series suggest that primary colorec- tal sarcomas are characterized by both rapid progression of all primary diagnosed colorectal malignancies [1]. Leio- and very poor oncological outcomes with a median of sur- myosarcomas appear to be the most common histological subtype of primary colorectal sarcomas with incidence up vival ranging from 30 to 53 months and a local recurrence rate of up to 85% [3–6]. Overall five-year survival rate of to 90%. More rare of their subtypes are liposarcomas, patients with primary colorectal sarcomas is significantly fibrous histiocytomas, and desmoplastic small cell tumors lower comparing to those with colorectal cancer—43% [2]. Regarding the small number of documented cases and 2 Case Reports in Oncological Medicine (a) (b) (c) Figure 1: Radiologic data from a high-resolution pelvic MRI. Tumor of the lower rectum (1) situated on the anterior wall was observed on sagittal (a) and axial T2-weighted scans (b) with signs of mesorectal invasion (blue arrowheads) ranging up to 3 mm and no radiologic features of lymph node metastases (3). Vaginal stump and rectovaginal sept (2) had a significantly low intensity MR signal due to their fibrotic transformation. On a series of diffusion-weighted images (c), a significant delay of diffusion together with intense signaling on high b-factors was observed at the level of a tumor (blue arrowheads). and 52%, respectively [7]. Tumor grade of primary colorec- identified. No radiological signs of either mesorectal fascia tal sarcomas is the most important prognostic factor for involvement or extramural vascular invasion (mrCRM and overall five-year survival—38% for high grade and 61% for mrEMVI ) had been observed (see Figures 1(a) and 1(b)). Vis- low grade [8]. Besides, inappropriate staging algorithm and ible mesorectal lymph nodes had homogenous MR signal, wide use of local excision as a surgical option for primary smooth external margins, and a regular size, thus showing no treatment results in high rates of R1 and R2 resections with radiologic signs of lymph node involvement (mrN ). It was a local recurrence rate of 12.7%. Nevertheless, a number of noticeable that the stump of the vagina and rectovaginal sept authors suggest that curative surgery should be the main had prominent signs of fibrosis regarding a highly intensive treatment option because data regarding chemotherapy MR signal on T2-weighted images. Malignant tumor features and radiation therapy is either lacking or it is controversial were also observed on a series of diffusion-weighted images [9, 10]. Colorectal sarcomas as a radiation-induced second (see Figure 1(c)). malignancy after cervical cancer treatment, on contrary to A CT scan with intravenous enhancement showed no primary ones, are an exceptionally rare entity. Up to date, signs of neither distant metastases neither thoracic or intra- only five cases had been described in the literature [11–15]. abdominal lymphadenopathy. Upper GI endoscopy and lab- In our current paper, we provide data on the sixth case of oratory data of standard blood, serum, and urine counts similar malignancy. revealed no signs of pathology. 2. Case Presentation 3. Surgical Treatment A 62-year-old female had a past medical history of FIGO stage IIB cervical cancer (squamous cell carcinoma Regarding past medical history, radiologic, endoscopic, and pT2bN0M0). In 1987, she underwent radical hysterectomy pathologic data, the patient was initially diagnosed with a with bilateral iliac lymph node dissection, followed by malignant nonepithelial lower rectal tumor of the unknown adjuvant radiation therapy—70 Gy external beam pelvic origin and staged as mrT3a mrN0 cM0. Being aware of pri- irradiation followed by 30.5 Gy of brachytherapy. Thirty- mary colorectal sarcomas, their recurrence and progression two years later, she presented with signs of rectal bleeding. patterns and a threatening rate of R1 and R2 resections, an Digital rectal examination revealed a solid exophytic institutional multidisciplinary board suggested curative sur- tumor on 5 cm above the anal verge. During rigid procto- gery as a primary treatment option. Total mesorectal excision sigmoidoscopy, a 3 cm anterior wall rectal tumor with (TME) with complete mesocolic excision and central vascu- irregular margins and swollen mucosa was observed. Addi- lar ligation (CME/CVL) carried by an open approach was tional flexible colonoscopy showed no signs of synchronous selected as proper extent of surgery. Standardized surgical colorectal neoplasms. Snare biopsy result showed an undif- technique in this case included complete left flexure mobili- ferentiated malignant nonepithelial tumor of unidentified zation, ligation of the inferior mesenteric artery at its origin histological origin. An attempt of immunohistochemistry near the aorta and inferior mesenteric vein just below the assay was undertaken unsuccessfully due to an insufficient pancreatic tail with consecutive total mesorectal excision up amount of tissue. to the level of the pelvic diaphragm (see Figure 2). Accurate Consecutively, a pelvic MRI with a 1.5 Tl Philips Intera TME procedure had been exacerbated by severe fibrotic machine had been performed for local staging. MERCURY changes of surrounding pelvic tissues due to postoperative protocol for high resolution imaging was applied. changes after iliac lymphadenectomy for cervical cancer On a series of sagittal and axial MR scans, a lower rectal and radiation-induced fibrosis as well. Regarding the signifi- tumor was observed on 4 cm above the anorectal junction with cant fibrotic transformation of the anterior rectal wall with maximal extent of 30 mm in the greatest dimension. Mesorec- adjacent tissues, an intraoperative decision was made to tal infiltration with maximal depth of 3 mm (mrT ) was also avoid reconstruction aware of an estimated high risk of 3b Case Reports in Oncological Medicine 3 4. Pathologic Findings Macroscopically, the tumor was represented an exophytic homogenous lesion 45 × 25 mm with irregular margins and ulcerated surface covered with clots of fibrin. The tumor originated from the muscular layer of the rectum with con- comitant mucosal invasion. Twelve regional lymph nodes were additionally examined. Initial histological appearance revealed a mixture of chaotic cellular and fibrotic vegeta- tions. Among them, a subgroup of heterogeneous polykar- yocytes with significant nuclear polymorphism (so called “monster cells”) was identified (see Figure 5). Those and other morphological features corresponded to a malignant low-grade mesenchymal tumor. All examined lymph nodes had no signs of metastases. In an attempt to identify the tissue of origin for a current tumor, an immunohistochemistry assay had been carried out. A panel of Ki-67, CD117, S100, smooth muscle actin (SMA), and desmin was used to conduct a differential diag- nosis between leiomyosarcoma and gastrointestinal stromal tumor. Tumor cells showed a high rate of mitotic activity with a 45% rate of Ki-67 expression (see Figure 6). There was a positive reaction for desmin and SMA in all samples (see Figures 7 and 8). On contrary, all samples had negative Figure 2: Resected gross specimen. 1: stump of the inferior reaction for CD117 and S100 (see Figures 9 and 10). As a mesenteric artery, 2: stump of the inferior mesenteric vein, 3: conclusion, the observed immunophenotype was identified preserved peritoneal window, 4: level of the peritoneal reflection, as a grade 3 leiomyosarcoma (ISD-code 8890/3). and 5: mesorectum. anastomotic leakage. Closure of the pelvic peritoneum was 5. Discussion avoided as well. On postoperative day 5, the patient developed such clin- In the current paper, we present the sixth case of radiation- ical signs as nausea, vomiting, and loss of flatus and stool. induced leiomyosarcoma of the rectum which developed 32 Computed tomography of the chest, abdomen, and pelvis years after completion of cervical cancer treatment. revealed multiple “levels” of gas and liquid throughout the Throughout the last decades, significant success was small intestine with a breakdown of peroral contrast at the achieved in the treatment of patients with pelvic malignan- level of distal ileal loop, which was situated at the cavity of cies, especially those who require either adjuvant or neoadju- minor pelvis, adherent to the stumps of both the rectum vant radiation therapy. As a consequence of overall survival and the vagina (see Figure 3). At that level, a noticeable defor- improvement, the problem of metachronous secondary mation of the intestinal loop with difference of luminal diam- malignancies among those patients who were exposed to eters was observed. On contrary, the lumen of a large radiation had arisen. According to the data of the National intestine was collapsed. Cancer Institute of USA, over 40% of all patients diagnosed By taking in regard both clinical and radiologic find- with primary malignancy will have to undergo radiation ings, the patient was diagnosed with postoperative ileus therapy [16]. Most of primary malignancies which require and an immediate reoperation had been carried out. Dur- radiation therapy as a treatment standard are breast, pros- ing abdominal examination, dilated intestinal loops with tate, cervical, rectal, and urinary bladder cancer. Among block of passage at the level of the pelvic diaphragm were long-term cancer survivors exposed to radiation, 16% are identified (see Figure 4). An adherent bowel wall was fixed at risk of developing a secondary malignancy. Recent data between vaginal and rectal stumps as it was previously from a SEER database suggests that 6–9.9% of all patients described on a series of CT scans. By the end of abdomi- who underwent radiation therapy for prostate cancer are at nal and pelvic exploration, no additional pathological find- a 34% risk of developing secondary lung, rectal, or urinary ings were observed. After detachment of adhesions, the bladder cancer. Majority of those patients develop secondary strangulated bowel was delivered back in the abdominal malignancies mostly after 10 years from treatment discon- cavity. Closure of the pelvis was performed with mobilized tinuation [17, 18]. body of the urinary bladder and remnant flaps of pelvic Cervical cancer remains one of the leading cause of peritoneum. Postoperative period was uneventful within cancer-related morbidity and mortality among females [19]. 30 days. The patient was safely discharged on postopera- It is known that only surgical treatment can be appropriate tive day 14 after initial surgery. At one year of follow- only in a relatively small subgroup of patients, particularly up, the patient is alive and has no radiological signs of among those who were initially diagnosed with FIGO stage neither local nor distant recurrence. IA1 (T1a1 by TNM) or less, i.e., with a depth of stromal 4 Case Reports in Oncological Medicine (a) (b) th Figure 3: Patient’s CT scans on the 6 postoperative day. Multiple intestinal “levels” of gas and fluid throughout the abdominal cavity were observed ((a), red arrowheads). Part of the distal intestinal loop with difference in lumen diameters was situated at the level of the pelvic floor ((b), yellow arrowheads) and was adherent to both rectal and vaginal stumps. Figure 6: Poorly differentiated malignant mesenchymal tumor. Immunohistochemistry assay with Ki-67 antibodies. Figure 4: Intraoperative photo during reoperation. Dilated intestinal loops up to the level of distal ileum (1) are observed. The loop of a strangulated bowel (2) was adherent to the stump of the rectum and vagina deep inside the pelvic cavity. Figure 7: Poorly differentiated malignant mesenchymal tumor. Immunohistochemistry assay with desmin antibodies. Positive reaction in tumor cells observed. invasion up to 3 mm and lateral spread up to 7 mm [20]. Recent NCCN guidelines suggest adjuvant radiation therapy for FIGO stage IA1 patients with a number of adverse risk features found at pathological examination, such as positive lymph nodes, parametrium invasion, or positive resection margins [21]. A standard approach for cervical cancer radia- tion therapy includes combination of external beam radia- Figure 5: Poorly differentiated malignant mesenchymal tumor. tion therapy and brachytherapy. Overall radiation dosage Multiple sites of cellular and nuclear polymorphism are observed. depends on the range of primary tumor spread—in cases of Hematoxylin-eosin staining, ×100. tumors below 40 mm in maximum dimension, the overall dosage consists of 80 Gy and ≥85 Gy if above 40 mm. Case Reports in Oncological Medicine 5 Figure 8: Poorly differentiated malignant mesenchymal tumor. Figure 10: Poorly differentiated malignant mesenchymal tumor. Immunohistochemistry assay with SMA antibodies. Positive Immunohistochemistry assay with S100 antibodies. Negative reaction in tumor cells observed. reaction in tumor cells observed. secondary malignancy development was the age under 30 years at primary diagnosis of cervical cancer. Urinary bladder (4.5), vagina (2.7), stomach (2.1), and hematopoietic tissue (2.5) had the highest relative risk for secondary malignancy. It was noticeable that the rectum had the lowest relative risk among other pelvic organs (1.8). Other data from a study of Samerdokiene et al. suggest that secondary radiation- induced malignancies occur in 5.3% of cervical patients after a combination of external beam and brachytherapy. Among them, rectal malignancies consisted only 8.6% [23]. A popu- lation study of 37,757 patients based on a data from SEER database demonstrated a 2.6-fold increase in a number of secondary malignancies among those cervical cancer patients Figure 9: Poorly differentiated malignant mesenchymal tumor. who underwent pelvic radiation therapy comparing to sur- Immunohistochemistry assay with CD117 antibodies. Negative gery alone [24]. Nevertheless, the authors acknowledged that reaction in tumor cells observed. metachronous bronchopulmonary, esophageal, and oropha- ryngeal cancer were mostly caused by continuous smoking In cases of cervical cancer, the radiation field includes and vaginal, vulval, and anal canal cancer—by HPV infection parametrium, sacrouterine ligaments, 3 cm of upper third rather than by previous radiation exposure. Similar retro- of the vagina below the tumor, and presacral, obturator, spective population-based data concerning a consistent pat- external, and internal iliac lymph nodes. By taking in regard tern of an increased secondary malignancy rate among all the anatomical relations of the cervix, it becomes clear that cervical cancer survivors was obtained from the Netherlands the most critical radiation sites are represented by the vagina, and Taiwan [25, 26]. Even though all secondary colon, rectal, the rectum, and the urinary bladder. In comparison, bony and anal malignancies in those studies were united in one pelvis structures receive significantly lesser radiation dosages. subgroup, their relative risk ratio still remained one of the A successful combination of curative surgery and highly lowest. A study by Ohno et al., based on a pooled data from precise modalities of radiation therapy in either adjuvant or 2167 patients after a combination of external beam and neoadjuvant regimens had given a unique opportunity to brachytherapy for cervical cancer, reports a 9.7% rate of sec- improve cervical cancer patient’s overall and disease-free sur- ondary radiation-induced malignancies with 19% of them vival rates like never before. Hence, by dropping out of a can- related to adjacent irradiated organs [27]. Soft tissue and cer recurrence group, those patients consequently enter bone sarcomas (22.0), leukemias (3.1), and urinary bladder another one—a risk group of developing a secondary malig- cancer (2.2) had the greatest relative risk rates. On the other nancy. The first population-based study which highlighted hand, rectal cancer, hepatocellular carcinoma, and gastric a relevance between previous exposure to pelvic irradiation cancer (1.0, 1.2 and, respectively) possessed the lowest rela- and a risk of developing a second malignancy was presented tive risk rates. Lim et al. came up with a data of 72,805 inva- by Boice et al., in 1984 [22]. The study included more than sive cervical cancer patients after pelvic irradiation within a 95,000 patients after pelvic radiation therapy for cervical study period of 7.34 years [28]. A 3.68% rate (2678 cases) cancer within a 30-year study period. This population was of secondary radiation-induced malignancies with similar compared with more than 99,000 patients who underwent relative risk patterns—vagina (9.36), soft tissues and bones only curative surgery. Throughout the study period, 3324 (2.7), vulva (2.58), and anus and anal canal (2.42)—was (3.5%) secondary radiation-induced malignancies had been observed. It is noticeable that among the 35 sites of secondary observed, of which 1622 (1.7%) were located at the organs malignancy occurrence, rectal cancer had the lowest relative covered by the irradiation field. The main risk factor of risk of 0.74. Correlation between previously treated cervical 6 Case Reports in Oncological Medicine Table 1: Pooled data of all identified case reports of radiation-induced leiomyosarcoma of the rectum after pelvic radiation therapy for cervical cancer. Time to diagnosis Year of Patient’s age Overall irradiation Radiation Selected treatment Authors of a secondary publication at diagnosis dosage (Gy) modality strategy malignancy (years) 40 Gy Intra-abdominal Drumea et al. [11] 1993 62 70 17 1 2 resection of the rectum EBRT +30 Gy BT Caporale et al. [12] 2003 N/A N/A N/A N/A N/A Intra-abdominal Basu et al. [13] 2012 79 N/A N/A 26 resection of the rectum Sigmostomy+ Garcia-Ortega 50 Gy 2018 58 85 8 chemotherapy+pelvic et al. [14] EBRT+35 Gy BT exenteration+vulvectomy Jayakumar et al. [15] 2015 58 N/A N/A 15 Local excision 70 Gy EBRT+ Current case report 2019 62 100.5 32 ТМЕ+CME/CVL 30.5 Gy BT 1 2 EBRT: external beam radiation therapy. BT: brachytherapy. cancer secondary colorectal cancer had been recently only in 12% of radiation-induced sarcomas. However, there highlighted in a paper of Rodriguez et al. [29]. After 35 years was absolutely no data regarding a radiation-induced leio- of follow-up, an estimated risk of colon cancer was 2.5% in a myosarcoma after previous pelvic radiation therapy with surgery alone group and 6.5% in a radiation therapy group. intra-abdominal or either intrapelvic localization. For rectal cancer, the difference was more significant—0.8% Remarkably, but up to date, there were only 5 published and 3.7%, respectively. Regression analysis survival model case reports of a radiation-induced leiomyosarcoma of the demonstrated a significant increase of relative risk for colon rectum in a patient after previous radiation therapy for cervi- cancer development after 8 years and rectal cancer—after cal cancer (see Table 1). On the contrary, one of the largest recent studies by Thiels et al. evaluates a series of 433 primary 15 years of follow-up. The authors suggest that 8 years should be a cutoff edge for colorectal cancer screening among cervi- colorectal sarcomas discovered within a 14-year observation cal cancer survivors. period [8]. Among the 29.3% of patients with the rectum as First studies about the influence of ionizing radiation on a primary tumor site, only 57.5% had leiomyosarcomas. the development of malignancies were provided after a Although radiation-induced leiomyosarcomas of the rectum appear to be an extremely rare type of secondary nuclear attack in Japan at 1945. Three main issues had been discovered then: tissues with higher proliferative index (i.e., malignancies, there is an emerging data suggesting an intrin- epithelial and hematopoietic) are mostly affected; very small sically different sequence of molecular events responsible for number of radiation-induced sarcomas and a ratio of 8%/1 their development and occurrence comparing to primary Gray, which is a distribution of those who shall develop a sarcomas [14]. Gonin-Laurent et al. recognize a mutation of ТР53 and RB1 genes as a key molecular event in the develop- malignancy among one hundred people exposed to an irradi- ation dosage of 1 Gy [30]. Mechanisms and conditions for ment of radiation-induced sarcomas. Consecutive mutation radiation sarcoma development were firstly described by of a TP53 gene was identified in 58% of radiation-induced Cahan et al. in 1948 [31]. It was noticed that the occurrence sarcomas and was related to deletion of other oncogenes in of pathologically confirmed secondary sarcomas is related 52% [34, 35]. It was also mentioned that mutation of a TP53 gene led to inactivation of RB1, which showed no signs to an irradiation field previously exposed to a dosage of at least 50 Gy. However, the only uncertainty was timing of of genetic alterations [35]. Hyperexpression of р53 is recog- occurrence which could range from months to decades. nized as a specific pathogenic route for radiation-induced Despite meeting all of Cahan’s criteria, radiation-induced sarcoma development as well. Taubert et al. identified a р53 sarcomas in cervical cancer patients after pelvic radiation mutation in 9 out of 11 radiation-induced sarcoma cases [36]. Finally, a study of Nakanishi et al. revealed a р53 muta- therapy are a very rare entity. Among all primary diagnosed soft tissue sarcomas, a range of 0.03% to 5.5% could be con- tion pattern in a series of 14 secondary radiation-induced soft sidered as radiation induced [32, 33]. tissue sarcomas in patients who previously underwent pelvic According to the largest published series of Cha et al., radiation therapy for cervical cancer [37]. Real-time poly- only 125 (2.5%) out of 4884 primary soft tissue sarcomas sat- merase chain reaction detected polymorphism of р53 gene with an 88% rate of mutations in exons 5, 7, 8, 12, and 18. isfied Cahan’s criteria and were considered as radiation induced [32]. Vast majority of those patients previously However, concomitant changes in the primary structure of underwent radiation therapy for breast cancer (29%), lym- a p53 protein were observed only in 31%. The authors con- phomas (16%), and prostate cancer (14%) with thoracic cav- clude that such a biological mislead might be a reason for a ity, thoracic wall, extremities, head and neck as a tumor site. long latency period between radiation exposure and clinical manifestation of secondary soft tissue sarcomas. Pathological features of leiomyosarcomas were identified Case Reports in Oncological Medicine 7 [9] C. D. Randleman, B. G. Wolff, R. R. Dozois, R. J. Spencer, L. H. 6. Conclusions Weiland, and D. M. Ilstrup, “Leiomyosarcoma of the rectum Among all radiation-induced malignancies affecting long- and anus,” International Journal of Colorectal Disease, vol. 4, term cervical cancer survivors, soft tissue sarcomas occur no. 2, pp. 91–96, 1989. quite frequently. However, radiation-induced leiomyosar- [10] B. D. Minsky, A. M. Cohen, S. I. Hajdu, and D. Nori, “Sphinc- coma of the rectum represents a remarkably rare case. ter preservation in rectal sarcoma,” Diseases of the Colon and Although primary colorectal sarcomas represent a very Rectum, vol. 33, no. 4, pp. 319–322, 1990. small subgroup of malignant mesenchymal tumors, the [11] K. Drumea, E. Sabo, E. Zuckerman, and J. E. Naschitz, “Leio- data regarding its proper treatment is lacking. On contrary myosarcoma of the colon in the aftermath of pelvic irradiation for endometrial carcinoma,” The American Journal of Gastro- to primary ones, radiation-induced sarcomas possess a enterology, vol. 88, article 1302, 1993. number of unique molecular features which make them [12] A. Caporale, F. Angelico, M. U. Cosenza et al., “A late compli- biologically different. We suggest that up to date, radical cation of pelvic radiotherapy: leiomyosarcoma of the rectum. surgery with curative intent, as it was performed in our Report of a case and review of the literature,” Hepatogastroen- study, is the most evidence-based treatment option for terology, vol. 50, no. 54, pp. 1933–1936, 2003. patients with radiation-induced sarcomas of the rectum. [13] I. Basu and P. Lemonas, “Leiomyosarcoma of the rectum fol- Fibrotic changes in the pelvis as a consequence of previous lowing pelvic irradiation: a difficult histological diagnosis,” external beam and brachytherapy may significantly jeopar- Annals of the Royal College of Surgeons of England, vol. 94, dise the completion of a TME procedure. That is why a no. 1, pp. e44–e45, 2012. two-step surgical strategy with delayed reconstruction [14] D. Y. Garcia-Ortega, N. Reyes-Garcia, H. Martinez-Said, C. H. should be taken in regard. S. Caro-Sanchez, and M. Cuellar-Hubbe, “Radiation-induced leiomyosarcoma of the rectum after cervical cancer treat- Consent ment,” Revista de Gastroenterología de México, vol. 83, no. 4, pp. 465–467, 2018. Before the publication of the present clinical case, the patient [15] R. Jayakumar, P. P. Basu, T. Huang, and C. A. Axiotis, “Post- filled out a written informed consent approving the use of her irradiation leiomyosarcoma of rectum presenting as a polyp: personal data in scientific purposes. case report and review of the literature,” International Journal of Surgical Pathology, vol. 24, no. 2, pp. 163–169, 2015. [16] L. B. Travis, C. S. Rabkin, L. M. Brown et al., “Cancer sur- Conflicts of Interest vivorship—genetic susceptibility and second primary can- cers: research strategies and recommendations,” JNCI: The authors declare that they have no conflicts of interest. Journal of the National Cancer Institute, vol. 98, no. 1, pp. 15–25, 2006. References [17] D. J. Brenner, R. E. Curtis, E. J. Hall, and E. Ron, “Second malig- nancies in prostate carcinoma patients after radiotherapy com- [1] M. Cuffy, F. Abir, and W. E. Longo, “Management of less com- pared with surgery,” Cancer, vol. 88, no. 2, pp. 398–406, 2000. mon tumors of the colon, rectum, and anus,” Clinical Colorec- [18] K. Moon, G. J. Stukenborg, J. Keim, and D. Theodorescu, tal Cancer, vol. 5, no. 5, pp. 327–337, 2006. “Cancer incidence after localized therapy for prostate cancer,” [2] S. Meijer, T. Peretz, J. J. Gaynor, C. Tan, S. I. Hajdu, and M. F. Cancer, vol. 107, no. 5, pp. 991–998, 2006. Brennan, “Primary colorectal sarcoma. A retrospective review [19] L. A. Torre, F. Bray, R. L. Siegel, J. Ferlay, J. Lortet-Tieulent, and prognostic factor study of 50 consecutive patients,” and A. Jemal, “Global cancer statistics, 2012,” CA: a Cancer Archives of Surgery, vol. 125, no. 9, pp. 1163–1168, 1990. Journal for Clinicians, vol. 65, no. 2, pp. 87–108, 2015. [3] K. C. Conlon, E. S. Casper, and M. F. Brennan, “Primary gas- [20] C. Marth, F. Landoni, S. Mahner et al., “Cervical cancer: ESMO trointestinal sarcomas: analysis of prognostic variables,” clinical practice guidelines for diagnosis, treatment and follow- Annals of Surgical Oncology, vol. 2, no. 1, pp. 26–31, 1995. up,” Annals of Oncology, vol. 28, supplement 4, pp. iv72–iv83, [4] C. L. Chou, S. C. Chang, T. C. Lin et al., “Clinical analysis and surgical results of primary colorectal sarcoma,” The Journal of [21] National Comprehensive Cancer Network, “Cervical cancer,” Society of Colon and Rectal Surgeons (Taiwan), vol. 21, pp. 161–168, 2010. 2019, https://www.nccn.org/professionals/physician_gls/pdf/ cervical.pdf. [5] P. Luna-Pérez, D. F. Rodríguez, L. Luján et al., “Colorectal sar- coma: analysis of failure patterns,” Journal of Surgical Oncol- [22] J. D. Boice Jr., N. E. Day, A. Andersen et al., “Second cancers ogy, vol. 69, no. 1, pp. 36–40, 1998. following radiation treatment for cervical cancer: an interna- tional collaboration among cancer registries,” JNCI: Journal [6] J. Yang, “Primary leiomyosarcoma in the colon: A case report,” of the National Cancer Institute, vol. 74, no. 5, pp. 955–975, Medicine (Baltimore), vol. 97, no. 7, 2018. [7] C. R. Cooper, B. F. Scully, and S. Lee-Kong, “Colorectal sar- coma: more than a gastrointestinal stromal tumor,” Transla- [23] V. Samerdokiene, K. P. Valuckas, E. Janulionis, V. Atkocius, and M. J. Rivard, “Second primary malignancies after radio- tional Gastroenterology and Hepatology, vol. 3, pp. 42–42, 2018. therapy including HDR Cf brachytherapy for cervical can- cer,” Brachytherapy, vol. 14, no. 6, pp. 898–904, 2015. [8] C. A. Thiels, J. R. Bergquist, A. C. Krajewski et al., “Outcomes of primary colorectal sarcoma: a National Cancer Data Base [24] R. E. Curtis, D. Michal Freedman, E. Ron et al., “New malig- (NCDB) review,” Journal of Gastrointestinal Surgery, vol. 21, nancies among cancer survivors: SEER cancer registries, no. 3, pp. 560–568, 2017. 1973–2000,” National Cancer Institute, 2006. 8 Case Reports in Oncological Medicine [25] M. Arnold, L. Liu, G. G. Kenter, C. L. Creutzberg, J. W. Coe- bergh, and I. Soerjomataram, “Second primary cancers in sur- vivors of cervical cancer in the Netherlands: implications for prevention and surveillance,” Radiotherapy and Oncology, vol. 111, no. 3, pp. 374–381, 2014. [26] C. J. Teng, L. K. Huon, Y. W. Hu et al., “Secondary primary malignancy risk in patients with cervical cancer in Taiwan: a nationwide population-based study,” Medicine, vol. 94, p. 43, [27] T. Ohno, S. Kato, S. Sato et al., “Long-term survival and risk of second cancers after radiotherapy for cervical cancer,” Interna- tional Journal of Radiation Oncology·Biology·Physics, vol. 69, no. 3, pp. 740–745, 2007. [28] M. C. Lim, Y. J. Won, J. Lim et al., “Second primary cancer after diagnosis and treatment of cervical cancer,” Cancer Research and Treatment, vol. 48, no. 2, pp. 641–649, 2016. [29] A. M. Rodriguez, Y.-F. Kuo, and J. S. Goodwin, “Risk of colo- rectal cancer among long-term cervical cancer survivors,” Medical Oncology, vol. 31, no. 5, p. 943, 2014. [30] E. J. Hall and C. S. Wuu, “Radiation-induced second cancers: the impact of 3D-CRT and IMRT,” International Journal of Radiation Oncology, Biology, Physics, vol. 56, no. 1, pp. 83– 88, 2003. [31] W. Cahan, H. Woodward, N. Higinbotham, F. W. Stewart, and B. L. Coley, “Sarcoma in irradiated bone. report of eleven cases,” Cancer, vol. 1, no. 1, pp. 3–29, 1948. [32] C. Cha, C. R. Antonescu, M. L. Quan, S. Maru, and M. F. Bren- nan, “Long-term results with resection of radiation-induced soft tissue sarcomas,” Annals of Surgery, vol. 239, no. 6, pp. 903–910, 2004. [33] A. Italiano, S. Bringer, J. Y. Blay et al., “Patterns of care and outcome radiation-induced soft tissue sarcomas,” Interna- tional Journal of Radiation Oncology·Biology·Physics, vol. 103, no. 2, pp. 449–452, 2019. [34] N. Gonin-Laurent, N. S. Hadj-Hamou, N. Vogt et al., “RB1 and TP53 pathways in radiation-induced sarcomas,” Oncogene, vol. 26, no. 41, pp. 6106–6112, 2007. [35] N. Gonin-Laurent, A. Gibaud, M. Huygue et al., “Specific TP53 mutation pattern in radiation-induced sarcomas,” Carcinogen- esis, vol. 27, no. 6, pp. 1266–1272, 2006. [36] H. Taubert, A. Meye, M. Bache et al., “p 53 status in radiation- induced soft-tissue sarcomas,” Strahlentherapie und Onkolo- gie, vol. 174, no. 8, pp. 427–430, 1998. [37] H. Nakanishi, Y. Tomita, A. Myoui et al., “Mutation of the p 53 gene in postradiation sarcoma,” Laboratory Investigation, vol. 78, no. 6, pp. 727–733, 1998. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018

Journal

Case Reports in Oncological MedicineHindawi Publishing Corporation

Published: Dec 10, 2019

References