- Email: [email protected]
Rare synchronous presentation and development of retroperitoneal dedifferentiated liposarcoma and rectal adenocarcinoma
Human Pathology: Case Reports 18 (2019) 200332
Contents lists available at ScienceDirect
Human Pathology: Case Reports journal homepage: www.elsevier.com/locate/ehpc
Case Report
Rare synchronous presentation and development of retroperitoneal dedifferentiated liposarcoma and rectal adenocarcinoma
T
⁎
Cyrus Parsa (D.O)a, , Robert Orlando (M.D., PhD)b, Krishna Narayanan (M.D.)c, Umakant M. Khetan (M.D.)c, Jin Guo (M.D.)a, Ravin Rupani (M.D.)d a
Department of Pathology, Western University of Health Sciences, 309 E. 2nd St., Pomona, CA, USA Department of Pathology, Beverly Hospital, 309 W. Beverly Blvd., Montebello, CA, USA c Department of Surgery, Beverly Hospital, 309 W. Beverly Blvd., Montebello, CA, USA d Department of Internal Medicine, Beverly Hospital, 309 W. Beverly Blvd., Montebello, CA, USA b
A R T I C LE I N FO
A B S T R A C T
Keywords: Multiple primary cancers Synchronous liposarcoma with colorectal cancer Soft-tissue sarcoma and adenocarcinomas
Multiple primary malignancies may occur as synchronous or meta-synchronous tumors in 2–17% of patients. Most multiple primary cancers occur in different locations of the same organ or in other organs such as lung, kidney, prostate, and bone. Occurrence of synchronous colorectal adenocarcinoma with liposarcoma, is exceptionally rare. A 79-year-old male presented with significant weight loss of 2–3 weeks duration following a transurethral resection of prostate. Colonoscopy, performed to determine source of the bleeding, revealed a fungating rectal mass, histologically diagnosed as a moderately differentiated adenocarcinoma. Biopsy of a large retroperitoneal mass, concurrently identified on an abdominal computed tomography (CT) scan, revealed a spindle cell neoplasm, subsequently confirmed as liposarcoma by immunohistochemical and molecular studies. Multiple imaging studies from eight years earlier, to as recent as one year (9 months) prior to the current hospital admission, were all negative for intestinal or peritoneal masses. The synchronous rare occurrence of these two malignancies presenting as large tumor masses within one year of negative abdominal imaging studies warrants consideration of mutual tumor promoting factors contributing to their pathogenesis or apparent rapid growth.
1. Introduction Depending on the original cancer site, multiple primary malignancies may occur in a cancer population between 2 and 17% of cases [1]. Colon cancer has been reported to occur with malignancies of other organs in 16.9% of patients [2,3]. The second primary foci have mainly been located in the digestive system, reproductive system, urinary system and respiratory system [4]. The occurrence of colonic adenocarcinoma with soft tissue sarcomas is exceptionally rare. Soft-tissue sarcomas (STS) represent a heterogeneous group of malignancies, accounting for < 1% of all malignant neoplasms in adults, variably characterized into different subtypes by their molecular events and epidemiology [5]. Retroperitoneal liposarcomas are specially rare, accounting for approximately 15% of all sarcomas with an overall incidence of 0.3% to 0.4% per 100,000, and peak incidence in the sixth and seventh decades without clear sex or racial predilection [6,7]. Excluding known syndromic associations such as Li–Fraumeni syndrome and neurofibromatosis, multiple primary neoplasms occur in STS at a rate of 7.5%, a significantly higher rate than that reported for the
⁎
occurrence of STS among the general cancer population (1%) [8]. The majority of cases occurs incidentally in a metachronous pattern and specially demonstrate risk for developing renal cell carcinomas [9,10]. In a study of 1845 patients with well-differentiated/dedifferentiated liposarcoma (WD/DD LPS), 75 (4.1%) had multiple concurrent or subsequent additional primary malignancies within 2 years (23 months) of initial diagnosis [11]. In most cases, the true timing of a second primary cancer in relation to WD/DD liposarcoma is unclear since liposarcomas are usually very large at the time of detection, with a typical size of 20–30 cm [12]. In another study of 312 consecutive patients with WD/DD LP diagnosis, 26 (8.3%) developed a second primary cancer either concurrent or within two years of the diagnosis [13]. The second cancers involved a variety of tissues and organs with colon (sigmoid) adenocarcinoma diagnosed in only one of the 26 patients with WD/DD LP. In one recent case study, concurrent sigmoid colon adenocarcinoma and small bowel mesentery dedifferentiated liposarcoma was described in a 62-year-old male [14].
Corresponding author. E-mail addresses: [email protected] (C. Parsa), [email protected] (J. Guo).
https://doi.org/10.1016/j.ehpc.2019.200332 Received 15 June 2019; Received in revised form 26 July 2019; Accepted 14 August 2019 2214-3300/ © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Human Pathology: Case Reports 18 (2019) 200332
C. Parsa, et al.
Fig. 4. Histologic sections of the resected retroperitoneal mass showed marked nuclear pleomorphism.
Fig. 1. CT of abdomen showing a large left retroperitoneal heterogeneous enhancing mass (X).
Fig. 5. Lipoblasts, present in some sections, support a diagnosis of liposarcoma. Fig. 2. A representative section of colonic wall with moderately differentiated adenocarcinoma.
Fig. 6. Diffuse MDM2 immunostain positivity provides further support for the diagnosis of dedifferentiated liposarcoma. Fig. 3. Needle biopsy of the retroperitoneal mass showing a spindle cell neoplasm.
rectal mass occupying about two thirds of the lumen at 18 cm from the anal verge. Biopsy of the rectal mass revealed moderately differentiated adenocarcinoma. A subsequent CT of abdomen revealed additional findings of an enlarged prostate gland, bilateral renal cysts, an elongated nonspecific nodule in the right lower lobe of lung, and a large (11 × 8 cm) heterogeneous enhancing mass in the left retroperitoneal hemiabdomen, suspicious for malignancy or metastasis (Fig. 1). Prior imaging studies including abdominal CT scans, 8 and 7 years earlier, and an abdominal x-ray and renal ultrasound from performed nine
2. Case report A 79-year-old male presented with complaints of 15–18 pound weight loss, poor appetite, dizziness and rectal bleeding of 2–3 weeks duration following transurethral resection of prostate. Colonoscopy, performed to determine source of the bleeding, revealed few diverticula in the left colon, multiple polyps in the right colon, and a fungating 2
Human Pathology: Case Reports 18 (2019) 200332
C. Parsa, et al.
a second colon, endometrial, ovarian, renal pelvis, stomach, ureteral, pancreatic and hepatobiliary malignancies. Synchronous occurrence of STS with colonic adenocarcinoma is exceedingly rare. Although there has been considerable insight regarding pathogenesis of colorectal adenocarcinomas, very little is known about the etiology or pathogenesis of retroperitoneal liposarcomas. No well established causative factor has been identified for liposarcomas. Many contributing factors can be hypothesized in the development of these tumors but are difficult to identify due to the rarity of the disease. Multiple genes in the 12q13-q15 regions including MDM2, CDK4, HMGA2, TSPAN31, OS1, OS9, CHOP, STAT6 and GLI, have also been implicated in their pathogenesis [18]. In conclusion, synchronous rapid growth of the two malignancies discussed in this paper, appearing within one year (9 months) of negative pelvic and abdominal imaging studies, warrants consideration of possible mutual tumor promoting factors, genetic links, host-tumor interaction, or immune derangement processes contributing to the rapid growth and/or pathogenesis of these two primary tumors.
months earlier, revealed no mention of a peritoneal mass. Core needle biopsies of the retroperitoneal mass revealed a spindle cell neoplasm interspersed with occasional adipocytes (Fig. 3), consistent with spindle cell sarcoma, possibly gastrointestinal stromal tumor (GIST) or dedifferentiated liposarcoma. Due to insufficient tumor in the tissue block, limited immunohistochemical (IHC) studies were then performed showing high Ki-67 (20%) and negative staining for CD117, arguing against GIST. A diagnostic laparoscopy was subsequently performed, followed by an open abdominal left hemicolectomy with tumor identified in the rectosigmoid region. The tumor was a moderately differentiated adenocarcinoma (Fig. 2), appeared to arise from a villous adenoma, and invaded through the muscularis propria into the pericolonic tissues (pT3) with benign regional lymph nodes and one tumor deposit (pN1c). The large retroperitoneal mass was then isolated lateral to the left kidney, inferior to the spleen, and posterior to an adherent splenic flexure of large intestine that had to be mobilized for resection of the mass. Lack of encapsulation and extremely friable tissue components necessitated excision of the tumor by piecemeal blunt and sharp dissection. Histologic sections of the mass showed marked nuclear pleomorphism (Fig. 4), lipoblasts (Fig. 5), and atypical mitoses consistent with grade 2–3 liposarcoma. Immunohistochemical studies were positive for: MDM-2 (Fig. 6), CDK4, p16, and BCL-2 (variably) with Ki-67 of 20%. The tumor cells were negative for: mesothelin, CK OSCAR, caldesmin, HMB45, MSA, PAX-8, SMA, SOX-10, ER, and CD99. Florescent in situ hybridization (FISH) was also positive for MDM2 amplification supporting the diagnosis of liposarcoma. Molecular studies by next-generation sequencing showed no evidence of expression of fusion RNA or mutations involving EWSR1, FUS, HMGA2 and PLAG1 genes. The colon cancer was diffusely positive (i.e. not deficient) by IHC for the mismatch repair (MMR) genes (MLH1, MLH2, MLH6, and PMS 2). CDK 4 and MDM-2 IHC studies of the colon cancer were negative. Repeat CT scan of abdomen, performed several days later, revealed a 4.6 × 4 cm mass in the left upper quadrant of abdomen at site of prior mass resection, consistent with residual tumor. CT-guided biopsy of this mass confirmed the presence of macroscopic residual liposarcoma (R2). According to the AJCC 8TH edition [15,16], the pathologic staging of this retroperitoneal sarcoma is R2 IIIB, based on the presence of macroscopic residual tumor, > 10 but ≤15 cm tumor size, and histologic grade of 2 or 3. Because of advanced age of the patient and inability to tolerate sarcoma therapy, hospice care was considered most appropriate approach in this patient's cancer care management.
References [1] A. Coyte, D.S. Morrison, P. McLoone, Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study, BMC Cancer 14 (2014) 272. [2] H.K. Weir, C.J. Johnson, T.D. Thompson, The effect of multiple primary rules on population-based cancer survival, Cancer Causes Control 24 (2013) 1231–1242. [3] H.K. Weir, C.J. Johnson, K.C. Ward, et al., The effect of multiple primary rules on cancer incidence rates and trends, Cancer Causes Control 27 (2016) 377–390. [4] A. Wu, S. He, J. Li, et al., Colorectal cancer in cases of multiple primary cancers: clinical features of 59 cases and point mutation analyses, Oncol. Lett. 13 (2017) 4720–4726. [5] F. Ducimetière, A. Lurkin, D. Ranchère-Vince, et al., Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing, PLoS One 6 (8) (2011). [6] C. Mettlin, R. Priore, U. Rao, Results of the national soft tissue sarcoma registry, J. Surg. Oncol. 19 (1982) 224–227. [7] I.R. Francis, R.H. Cohan, D.G.K. Varma, et al., Retroperitoneal sarcomas, Cancer Imaging 5 (2005) 89–94. [8] S.R. Grobmyer, N. Luther, C. Antonescu, et al., Multiple primary soft tissue sarcomas, Cancer 101 (2004) 2633–2635. [9] O. Merimsky, Y. Kollender, J. Issakov, et al., Multiple primary malignancies in association with soft tissue sarcomas, Cancer 91 (2001) 1363–1371. [10] J.R. Lex, A. Aoude, J.D. Stevenson, et al., Multiple soft tissue sarcomas in a single patient: an international multicentre review, Sarcoma 2018 (2018) 7 pages. [11] Curtis RE, Freedman DM, Ron E, et al (eds). New Malignancies among Cancer Survivors: SEER Cancer Registries, 1973–2000. National Cancer Institute, (NIH Publ. 2006. No. 05-5302). [12] E. Fabre-Guillevin, J.M. Coindre, S. Somerhausen Nde, et al., Retroperitoneal liposarcomas: followup analysis of dedifferentiation after clinicopathologic reexamination of 86 liposarcomas and malignant fibrous histiocytomas, Cancer 106 (2006) 2725–2733. [13] E. Jung, M. Fiore, A. Gronchi, et al., Second primary malignancies in patients with well differentiated/dedifferentiated Liposarcoma, Anticancer Res. 38 (2018 Jun) 3535–3542. [14] E.E. Jung, F.S. Heinemann, C.A. Egelston, et al., Synchronous recurrence of concurrent colon adenocarcinoma and dedifferentiated liposarcoma, BMJ 12 (2019) Case Reports CP. (e228868). [15] M.B. Amin, S.B. Edge, F.L. Greene, et al. (Eds.), AJCC Cancer Staging Manual, 8th ed, Springer, New York, NY, 2017. [16] F. Malik, M.R. Clay, Staging - sarcomas of the retroperitoneum, PathologyOutlines. com website https://www.pathologyoutlines.com/topic/ softtissuestagingretroperitoneum.html Accessed July 26th (2019). [17] A.M. VanderWalde, A. Hurria, Second malignancies among elderly survivors of cancer, Oncologist. 16 (2011) 1572–1581. [18] R.J. Rieker, J. Weitz, B. Lehner, et al., Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow separate molecular pathways, Virchows Arch. 456 (2010) 277.
3. Discussion The risks for synchronous and metasynchronous solid malignancies are significantly greater following a wide variety of primary tumors among older adults. The higher risk may be attributed to a genetic predisposition to multiple cancers or shared risk factors such as tobacco, alcohol, or side effects of treatment modalities of the original cancer [17]. Multiple primary tumors, especially those occurring synchronously and without history of chemotherapy or radiation therapy, are uncommon and most often involve epithelial malignancies. Patients with clinical history of multiple synchronous or metachronous cancers involving colon are likely to have a familial cancer syndrome (e.g. Lynch syndrome, Hereditary nonpolyposis colorectal cancer, or familial adenomatous polyposis) that may be associated with
3
Contents lists available at ScienceDirect
Human Pathology: Case Reports journal homepage: www.elsevier.com/locate/ehpc
Case Report
Rare synchronous presentation and development of retroperitoneal dedifferentiated liposarcoma and rectal adenocarcinoma
T
⁎
Cyrus Parsa (D.O)a, , Robert Orlando (M.D., PhD)b, Krishna Narayanan (M.D.)c, Umakant M. Khetan (M.D.)c, Jin Guo (M.D.)a, Ravin Rupani (M.D.)d a
Department of Pathology, Western University of Health Sciences, 309 E. 2nd St., Pomona, CA, USA Department of Pathology, Beverly Hospital, 309 W. Beverly Blvd., Montebello, CA, USA c Department of Surgery, Beverly Hospital, 309 W. Beverly Blvd., Montebello, CA, USA d Department of Internal Medicine, Beverly Hospital, 309 W. Beverly Blvd., Montebello, CA, USA b
A R T I C LE I N FO
A B S T R A C T
Keywords: Multiple primary cancers Synchronous liposarcoma with colorectal cancer Soft-tissue sarcoma and adenocarcinomas
Multiple primary malignancies may occur as synchronous or meta-synchronous tumors in 2–17% of patients. Most multiple primary cancers occur in different locations of the same organ or in other organs such as lung, kidney, prostate, and bone. Occurrence of synchronous colorectal adenocarcinoma with liposarcoma, is exceptionally rare. A 79-year-old male presented with significant weight loss of 2–3 weeks duration following a transurethral resection of prostate. Colonoscopy, performed to determine source of the bleeding, revealed a fungating rectal mass, histologically diagnosed as a moderately differentiated adenocarcinoma. Biopsy of a large retroperitoneal mass, concurrently identified on an abdominal computed tomography (CT) scan, revealed a spindle cell neoplasm, subsequently confirmed as liposarcoma by immunohistochemical and molecular studies. Multiple imaging studies from eight years earlier, to as recent as one year (9 months) prior to the current hospital admission, were all negative for intestinal or peritoneal masses. The synchronous rare occurrence of these two malignancies presenting as large tumor masses within one year of negative abdominal imaging studies warrants consideration of mutual tumor promoting factors contributing to their pathogenesis or apparent rapid growth.
1. Introduction Depending on the original cancer site, multiple primary malignancies may occur in a cancer population between 2 and 17% of cases [1]. Colon cancer has been reported to occur with malignancies of other organs in 16.9% of patients [2,3]. The second primary foci have mainly been located in the digestive system, reproductive system, urinary system and respiratory system [4]. The occurrence of colonic adenocarcinoma with soft tissue sarcomas is exceptionally rare. Soft-tissue sarcomas (STS) represent a heterogeneous group of malignancies, accounting for < 1% of all malignant neoplasms in adults, variably characterized into different subtypes by their molecular events and epidemiology [5]. Retroperitoneal liposarcomas are specially rare, accounting for approximately 15% of all sarcomas with an overall incidence of 0.3% to 0.4% per 100,000, and peak incidence in the sixth and seventh decades without clear sex or racial predilection [6,7]. Excluding known syndromic associations such as Li–Fraumeni syndrome and neurofibromatosis, multiple primary neoplasms occur in STS at a rate of 7.5%, a significantly higher rate than that reported for the
⁎
occurrence of STS among the general cancer population (1%) [8]. The majority of cases occurs incidentally in a metachronous pattern and specially demonstrate risk for developing renal cell carcinomas [9,10]. In a study of 1845 patients with well-differentiated/dedifferentiated liposarcoma (WD/DD LPS), 75 (4.1%) had multiple concurrent or subsequent additional primary malignancies within 2 years (23 months) of initial diagnosis [11]. In most cases, the true timing of a second primary cancer in relation to WD/DD liposarcoma is unclear since liposarcomas are usually very large at the time of detection, with a typical size of 20–30 cm [12]. In another study of 312 consecutive patients with WD/DD LP diagnosis, 26 (8.3%) developed a second primary cancer either concurrent or within two years of the diagnosis [13]. The second cancers involved a variety of tissues and organs with colon (sigmoid) adenocarcinoma diagnosed in only one of the 26 patients with WD/DD LP. In one recent case study, concurrent sigmoid colon adenocarcinoma and small bowel mesentery dedifferentiated liposarcoma was described in a 62-year-old male [14].
Corresponding author. E-mail addresses: [email protected] (C. Parsa), [email protected] (J. Guo).
https://doi.org/10.1016/j.ehpc.2019.200332 Received 15 June 2019; Received in revised form 26 July 2019; Accepted 14 August 2019 2214-3300/ © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Human Pathology: Case Reports 18 (2019) 200332
C. Parsa, et al.
Fig. 4. Histologic sections of the resected retroperitoneal mass showed marked nuclear pleomorphism.
Fig. 1. CT of abdomen showing a large left retroperitoneal heterogeneous enhancing mass (X).
Fig. 5. Lipoblasts, present in some sections, support a diagnosis of liposarcoma. Fig. 2. A representative section of colonic wall with moderately differentiated adenocarcinoma.
Fig. 6. Diffuse MDM2 immunostain positivity provides further support for the diagnosis of dedifferentiated liposarcoma. Fig. 3. Needle biopsy of the retroperitoneal mass showing a spindle cell neoplasm.
rectal mass occupying about two thirds of the lumen at 18 cm from the anal verge. Biopsy of the rectal mass revealed moderately differentiated adenocarcinoma. A subsequent CT of abdomen revealed additional findings of an enlarged prostate gland, bilateral renal cysts, an elongated nonspecific nodule in the right lower lobe of lung, and a large (11 × 8 cm) heterogeneous enhancing mass in the left retroperitoneal hemiabdomen, suspicious for malignancy or metastasis (Fig. 1). Prior imaging studies including abdominal CT scans, 8 and 7 years earlier, and an abdominal x-ray and renal ultrasound from performed nine
2. Case report A 79-year-old male presented with complaints of 15–18 pound weight loss, poor appetite, dizziness and rectal bleeding of 2–3 weeks duration following transurethral resection of prostate. Colonoscopy, performed to determine source of the bleeding, revealed few diverticula in the left colon, multiple polyps in the right colon, and a fungating 2
Human Pathology: Case Reports 18 (2019) 200332
C. Parsa, et al.
a second colon, endometrial, ovarian, renal pelvis, stomach, ureteral, pancreatic and hepatobiliary malignancies. Synchronous occurrence of STS with colonic adenocarcinoma is exceedingly rare. Although there has been considerable insight regarding pathogenesis of colorectal adenocarcinomas, very little is known about the etiology or pathogenesis of retroperitoneal liposarcomas. No well established causative factor has been identified for liposarcomas. Many contributing factors can be hypothesized in the development of these tumors but are difficult to identify due to the rarity of the disease. Multiple genes in the 12q13-q15 regions including MDM2, CDK4, HMGA2, TSPAN31, OS1, OS9, CHOP, STAT6 and GLI, have also been implicated in their pathogenesis [18]. In conclusion, synchronous rapid growth of the two malignancies discussed in this paper, appearing within one year (9 months) of negative pelvic and abdominal imaging studies, warrants consideration of possible mutual tumor promoting factors, genetic links, host-tumor interaction, or immune derangement processes contributing to the rapid growth and/or pathogenesis of these two primary tumors.
months earlier, revealed no mention of a peritoneal mass. Core needle biopsies of the retroperitoneal mass revealed a spindle cell neoplasm interspersed with occasional adipocytes (Fig. 3), consistent with spindle cell sarcoma, possibly gastrointestinal stromal tumor (GIST) or dedifferentiated liposarcoma. Due to insufficient tumor in the tissue block, limited immunohistochemical (IHC) studies were then performed showing high Ki-67 (20%) and negative staining for CD117, arguing against GIST. A diagnostic laparoscopy was subsequently performed, followed by an open abdominal left hemicolectomy with tumor identified in the rectosigmoid region. The tumor was a moderately differentiated adenocarcinoma (Fig. 2), appeared to arise from a villous adenoma, and invaded through the muscularis propria into the pericolonic tissues (pT3) with benign regional lymph nodes and one tumor deposit (pN1c). The large retroperitoneal mass was then isolated lateral to the left kidney, inferior to the spleen, and posterior to an adherent splenic flexure of large intestine that had to be mobilized for resection of the mass. Lack of encapsulation and extremely friable tissue components necessitated excision of the tumor by piecemeal blunt and sharp dissection. Histologic sections of the mass showed marked nuclear pleomorphism (Fig. 4), lipoblasts (Fig. 5), and atypical mitoses consistent with grade 2–3 liposarcoma. Immunohistochemical studies were positive for: MDM-2 (Fig. 6), CDK4, p16, and BCL-2 (variably) with Ki-67 of 20%. The tumor cells were negative for: mesothelin, CK OSCAR, caldesmin, HMB45, MSA, PAX-8, SMA, SOX-10, ER, and CD99. Florescent in situ hybridization (FISH) was also positive for MDM2 amplification supporting the diagnosis of liposarcoma. Molecular studies by next-generation sequencing showed no evidence of expression of fusion RNA or mutations involving EWSR1, FUS, HMGA2 and PLAG1 genes. The colon cancer was diffusely positive (i.e. not deficient) by IHC for the mismatch repair (MMR) genes (MLH1, MLH2, MLH6, and PMS 2). CDK 4 and MDM-2 IHC studies of the colon cancer were negative. Repeat CT scan of abdomen, performed several days later, revealed a 4.6 × 4 cm mass in the left upper quadrant of abdomen at site of prior mass resection, consistent with residual tumor. CT-guided biopsy of this mass confirmed the presence of macroscopic residual liposarcoma (R2). According to the AJCC 8TH edition [15,16], the pathologic staging of this retroperitoneal sarcoma is R2 IIIB, based on the presence of macroscopic residual tumor, > 10 but ≤15 cm tumor size, and histologic grade of 2 or 3. Because of advanced age of the patient and inability to tolerate sarcoma therapy, hospice care was considered most appropriate approach in this patient's cancer care management.
References [1] A. Coyte, D.S. Morrison, P. McLoone, Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study, BMC Cancer 14 (2014) 272. [2] H.K. Weir, C.J. Johnson, T.D. Thompson, The effect of multiple primary rules on population-based cancer survival, Cancer Causes Control 24 (2013) 1231–1242. [3] H.K. Weir, C.J. Johnson, K.C. Ward, et al., The effect of multiple primary rules on cancer incidence rates and trends, Cancer Causes Control 27 (2016) 377–390. [4] A. Wu, S. He, J. Li, et al., Colorectal cancer in cases of multiple primary cancers: clinical features of 59 cases and point mutation analyses, Oncol. Lett. 13 (2017) 4720–4726. [5] F. Ducimetière, A. Lurkin, D. Ranchère-Vince, et al., Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing, PLoS One 6 (8) (2011). [6] C. Mettlin, R. Priore, U. Rao, Results of the national soft tissue sarcoma registry, J. Surg. Oncol. 19 (1982) 224–227. [7] I.R. Francis, R.H. Cohan, D.G.K. Varma, et al., Retroperitoneal sarcomas, Cancer Imaging 5 (2005) 89–94. [8] S.R. Grobmyer, N. Luther, C. Antonescu, et al., Multiple primary soft tissue sarcomas, Cancer 101 (2004) 2633–2635. [9] O. Merimsky, Y. Kollender, J. Issakov, et al., Multiple primary malignancies in association with soft tissue sarcomas, Cancer 91 (2001) 1363–1371. [10] J.R. Lex, A. Aoude, J.D. Stevenson, et al., Multiple soft tissue sarcomas in a single patient: an international multicentre review, Sarcoma 2018 (2018) 7 pages. [11] Curtis RE, Freedman DM, Ron E, et al (eds). New Malignancies among Cancer Survivors: SEER Cancer Registries, 1973–2000. National Cancer Institute, (NIH Publ. 2006. No. 05-5302). [12] E. Fabre-Guillevin, J.M. Coindre, S. Somerhausen Nde, et al., Retroperitoneal liposarcomas: followup analysis of dedifferentiation after clinicopathologic reexamination of 86 liposarcomas and malignant fibrous histiocytomas, Cancer 106 (2006) 2725–2733. [13] E. Jung, M. Fiore, A. Gronchi, et al., Second primary malignancies in patients with well differentiated/dedifferentiated Liposarcoma, Anticancer Res. 38 (2018 Jun) 3535–3542. [14] E.E. Jung, F.S. Heinemann, C.A. Egelston, et al., Synchronous recurrence of concurrent colon adenocarcinoma and dedifferentiated liposarcoma, BMJ 12 (2019) Case Reports CP. (e228868). [15] M.B. Amin, S.B. Edge, F.L. Greene, et al. (Eds.), AJCC Cancer Staging Manual, 8th ed, Springer, New York, NY, 2017. [16] F. Malik, M.R. Clay, Staging - sarcomas of the retroperitoneum, PathologyOutlines. com website https://www.pathologyoutlines.com/topic/ softtissuestagingretroperitoneum.html Accessed July 26th (2019). [17] A.M. VanderWalde, A. Hurria, Second malignancies among elderly survivors of cancer, Oncologist. 16 (2011) 1572–1581. [18] R.J. Rieker, J. Weitz, B. Lehner, et al., Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow separate molecular pathways, Virchows Arch. 456 (2010) 277.
3. Discussion The risks for synchronous and metasynchronous solid malignancies are significantly greater following a wide variety of primary tumors among older adults. The higher risk may be attributed to a genetic predisposition to multiple cancers or shared risk factors such as tobacco, alcohol, or side effects of treatment modalities of the original cancer [17]. Multiple primary tumors, especially those occurring synchronously and without history of chemotherapy or radiation therapy, are uncommon and most often involve epithelial malignancies. Patients with clinical history of multiple synchronous or metachronous cancers involving colon are likely to have a familial cancer syndrome (e.g. Lynch syndrome, Hereditary nonpolyposis colorectal cancer, or familial adenomatous polyposis) that may be associated with
3