Primary sigmoid squamous cell carcinoma with liver metastasis: A case report

lNTRODUCTlON

Colorectal malignancies are among the most common malignancies worldwide[1], and their most common pathological type is adenocarcinoma[2], followed by adenosquamous carcinoma. Squamous carcinoma alone is rare, accounting for approximately 0.1 to 0.25 per 1000 of all colorectal cancers[3]. Squamous cell carcinoma (SCC) of the colon was first reported in the German literature published in 1919[4]. Ozuner

[5] reported 11 cases of squamous carcinoma of the colon, of which eight were squamous carcinoma of the rectum, two were squamous carcinoma of the ascending colon, and only one was squamous carcinoma of the sigmoid colon. In 2019, researchers[6] compiled the Surveillance, Epidemiology, and End Results (SEER) database for the period 1998-2012 and analyzed its clinical staging and other characteristics. A total of 464 patients were diagnosed with squamous carcinoma of the colon, of which only 50 (10.8%) patients had squamous carcinoma of the colon. The pathogenesis of colonic squamous carcinoma is unclear, and its prognosis is worse than that of simple adenocarcinoma[7]. Most studies have been limited to case reports, and there are no standard treatment protocols.

Herein, we reported a case of primary SCC of the sigmoid colon with liver metastasis. This study aimed to analyze and study the characteristics of this case and summarize the clinical characteristics, pathological features, and treatment of squamous carcinoma of the colon to improve our understanding of such disease.

CASE PRESENTATlON

Chief complaints

A 56-year-old woman presented to our gastrointestinal surgery clinic in March 2019 who complained of constipation for 2 years.

History of present illness

The patient complained of a history of constipation, with stools 3-5 d/once, requiring oral laxatives for 2 years.

History of past illness

The patient was previously physically fit.

Personal and family history

The authors declare that they have no conflict of interest.

Physical examination

But life did not depart from him- the thread would not break,but the thread of memory was severed; the thread of his mind hadbeen cut through, and what was still more grievous, a body remained- a living healthy body that wandered about like a troubled spirit.

What happens now is that whenever we go out together, with my outstretched arms tightly clinging to my wife s shoulder, I m pretty much like a monker hanging on to a wise pole, allowing her to drag me along the street ...

Laboratory examinations

Laboratory tests were unremarkable (Table 1).

Imaging examinations

The patient underwent computed tomography examination, which confirmed the presence of an irregular soft tissue mass located in the left lower abdomen with unclear borders and nonuniform density (Figure 1A) and the absence of metastatic lesions in the liver (Figure 1B). Total colonoscopy was advised, which indicated the presence of an ulcerated mass with infiltrative growth in the colon approximately 30 cm from the anus (Figure 2). Pathological examination of the tissue obtained by colonoscopy revealed squamous carcinoma (Figure 3).

Pathologic evaluation

A biopsy was performed at colonoscopy, and histology showed squamous carcinoma.

I looked up in horror and disbelief. There was Justin on the roof of the house, filling his plastic bucket with the ripe juicy plums from his favorite tree.

As soon as the sun rose the King came, and when he perceived the gold he was astonished and delighted, but his heart only lusted4 more than ever after the precious metal

FlNAL DlAGNOSlS

The patient underwent combined partial ileal and anterior peritoneal resection for sigmoid colon cancer on March 28, 2019. The sigmoid colon was incised 12 cm from the proximal edge and 6 cm from the distal edge of the tumor. Intraoperatively, the mass invaded the anterior peritoneum and ileum approximately 40 cm from the ileocecal region and was resected.

Commonly used treatments for colorectal cancer include surgery, radiotherapy, and chemotherapy. Owing to its extremely low incidence rate, there is no clear standard treatment plan for SCC. Some case reports have suggested chemoradiotherapy as the initial treatment and surgery as the treatment in case of poor chemotherapy effect or tumor recurrence because chemoradiotherapy can effectively control rectal squamous carcinoma well[28,29]. Zhao

[13] reported a patient with ascending colon squamous carcinoma combined with rectal adenocarcinoma who received two cycles of neoadjuvant chemotherapy based on gemcitabine, combined with oxaliplatin and capecitabine, and experienced disease stabilization. Surgery was performed in this patient. The original regimen was continued for six cycles of chemotherapy after surgery, and progression-free survival exceeded 10 mo after treatment.

Eight lymph nodes were examined, and no lymph node metastasis was observed on postoperative pathology. The results of the preoperative examination suggested no distant organ metastasis, such as liver, lung, or brain metastasis. Combining the above information on histopathological specimens, lymph nodes, and distant metastases, the stage of sigmoid squamous carcinoma was determined to be pT4bN0M0, stage IIC.

TREATMENT

The patient was diagnosed with early-stage colon cancer, and surgical treatment was preferred, without prior systematic treatment. After surgical treatment, the patient received six cycles of postoperative adjuvant chemotherapy.

OUTCOME AND FOLLOW-UP

Postoperatively, the patient recovered well, without complications. Routine chemotherapy and regular follow-up were performed postoperatively. On November 10, 2019, multiple liver metastases (Figure 7A) and an anterior pelvic mass (Figure 7B) were observed. A liver biopsy was performed immediately after the discovery of liver metastases, and the pathological results showed that it was a metastatic SCC derived from the liver (Figure 8). Genetic testing revealed the presence of somatic mutations (Table 2). Unfortunately, the liver cannot be surgically removed because of multiple metastases. The patient did not undergo radiofrequency or ablation therapy. However, I

seed implantation was performed on the abdominal wall mass. After seed implantation, two cycles of firstline chemotherapy were administered. By May 2020, the patient had died of the tumor. The patient’s overall survival rate was 14 mo.

The patient had no positive signs.

DlSCUSSlON

SCC occurs most often in areas covered by squamous cells; therefore, it rarely occurs in organs without squamous cell coverage. The colon is not covered by squamous epithelium and is dominated by glandular epithelium. Therefore, SCC in the primary colon is significantly rare, with an incidence of approximately 0.025-0.1 per 1000 colon cancers[8]. Regarding the high incidence age of colorectal squamous carcinoma, Donato-Brown

[6] reported that the average age for the entire cohort in the SEER database was 60.7 ± 13.7 years, and the median age of onset of colonic SCC was 55-60 years according to the literature[9-15]. SCC can occur in any part of the colorectum[5,16]; the majority of them are located in the rectum (93.4%), followed by the right hemicolon (3.4%), and SCC in the left hemicolon is extremely rare. The first reported SCC of the colon in China also occurred in the ascending colon[17]. The clinical manifestations of patients with colorectal squamous carcinoma are similar to those of adenocarcinoma, mainly including abdominal pain, blood in the stool, and change in bowel habits, and a few may present with acute abdominal and intestinal obstructions[9]. We reported a case of simple squamous carcinoma of the sigmoid colon, the main clinical manifestation of which was chronic constipation without blood in the stool or abdominal pain.

The possible mechanisms of colonic squamous carcinoma pathogenesis are currently reported in the literature with the following possibilities. First, squamous metaplasia of the glandular epithelium is commonly caused by chronic inflammation due to radiation therapy[18], schistosomiasis infection[19], and inflammatory bowel disease[17], and squamous cell metaplasia is caused by continuous chronic stimulation of the glandular epithelium, which in turn leads to cell degeneration and carcinoma, as reported by Cheng

[20] in a 51-year-old female patient with squamous colorectal cancer who had a history of ulcerative colitis for more than 10 years with a long history of hormonal therapy. Second is the pathological process of undifferentiated cell proliferation, squamous differentiation, and carcinogenesis. Comer

[21] suggested that basal cells undergo proliferation and repair after colorectal epithelial damage, whereas repeated destructive effects cause basal cells to lose their normal differentiation ability and produce adenocarcinoma, squamous carcinoma, or adenosquamous carcinoma. Michelassi

[22] proposed that SCC originates from undifferentiated basal cells after mucosal damage proliferation and malignant transformation. Third, adenoma or adenocarcinoma cells differentiate into squamous carcinoma, and squamous cells have been gradually recognized in colonic adenomas[23]. Cramer

[24] reported three cases of colonic adenomas in which multipotential reserve cells were found to differentiate into squamous epithelium, and primary colonic SCC may originate from squamous cell differentiation and carcinoma of cells within the adenoma. Fourth, considering ectopic ectodermal cell nest carcinoma, Gooneratne

[25] reported a case of SCC of the sigmoid colon originating from a malignant teratoma of the ovary. Fifth, residual implantation of squamous cell epithelial cells is more common due to trauma and surgery[26].

One night, the boy really missed the girl. When he called her however, the girl s cell phone was off because she was already asleep. The next day, the boy asked the girl to leave her cell phone on at night because when he needed to find her and could not, he would be worried.

Informed written consent was obtained from the patient for publication of this report and any accompanying images.

He paused and then went on, I remember the day I decided6 I was too old for a goodbye kiss. When we got to the school and came to a stop, he had his usual big smile. He started to lean toward me, but I put my hand up and said, No, Dad.

The specimen was embedded in paraffin and cut into 4-μm-thick sections. Hematoxylin and eosin staining was performed, and the sections were examined microscopically at the Pathology Department of the Affiliated Hospital of Chengde Medical College. Histologically, the tumor cells were arranged in irregular nest-like clusters, the tumor cells were ill-defined, the nucleoplasm ratio was disordered, the nuclei were large and densely stained, the polar direction disappeared, the nuclear membrane was clear, and the chromatin was concentrated, consistent with the diagnosis of intermediate-to-low differentiated squamous carcinoma (Figure 4A and B). The cancerous tissue had invaded the entire layer of the intestinal wall (Figure 5), and no residual cancer was observed on the upper and lower incision margins. Immunohistochemically, the cancer cells were negative for C-erbb-2, bcl-2, COX2, CDX2 (Figure 6A), PS2, and CK7. These cells were positive for MSH2, PMS2, MSH6, MLH1, P53, EGFR, P40 (Figure 6B), CK5/CK6 (Figure 6C), D2-40, CD34, and TOPII. The Ki-67 proliferation index was 70%.

SCC of the colon is rare; the sigmoid colon is even rarer, and its treatment is mostly referred to as adenocarcinoma of the colon. We reported the case of a patient with squamous carcinoma of the sigmoid colon who developed liver metastases and pelvic metastases 7 mo after surgery and postoperative chemotherapy treatment, which showed poor sensitivity to conventional chemotherapy regimens for colorectal adenocarcinoma. Therefore, summarizing the case characteristics and treatment experience of patients with colonic squamous carcinoma and determining a more suitable chemotherapy regimen for colonic squamous carcinoma to improve the survival time of such patients are the main issues to be explored in the future.

The following conditions should be met to establish the diagnosis of colorectal SCC[27]: first, consistent with the pathological features of SCC without adenoid differentiation; second, ruling out the possibility of metastasis or direct invasion of other tissues or organs by SCC; third, ruling out the possibility of upward extension of SCC of the anal canal to the lower rectum; and fourth, absence of long-term persistent squamous cell epithelium-lined fistula in the intestinal canal where the tumor is located.

CONCLUSlON

Colon SCC, especially sigmoid colon SCC, is one of the rare lesions encountered by surgeons and pathologists. Due to its rarity, it is easily misdiagnosed. Here, we reported the case of a patient with sigmoid SCC at stage IIC (pT4bN0M0). Colon SCC appears to have a worse prognosis and no standard treatment options; therefore, determining the accurate diagnosis and appropriate management of SCC is important.

FOOTNOTES

Li XY was responsible for follow-up of the patient, reviewed the literature and contributed to drafting the manuscript; Teng G was responsible for follow-up of the patient; Zhao X was the pathologist involved in the patient’s diagnosis; Zhu CM was responsible for revision of the manuscript for important intellectual content, contributed to manuscript drafting and revision; all authors approved the final version of the paper prior to submission.

Hebei Province Talent Training Project, No. A201902016.

In this case, the tumor was 30 cm away from the anal verge, excluding cloacogenic embryologic nests as origins of the SCC. The patient had no specific past medical history, no evidence of SCC on imaging, and no colonic fistula formation. After three pathological examinations, both the primary lesion and liver metastases showed simple SCC on hematoxylin and eosin staining. Positive AE1/AE3 suggests an epithelial origin tumor; positive p40 and CK5/CK6 suggest SCC, negative CDX2 rules out the possibility of adenocarcinoma; and negative CGA and Syn rule out neuroendocrine origin. Immunohistochemistry was consistent with the pathology of primary SCC.

Well, thought the youth as he read this proclamation, that ought not to be a very difficult matter; and he asked an audience of the king, and told him that he wished to seek for the princess

Personal and family histories were not exceptional.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

27.Best silver tankard: A tankard is a large drinking vessel62 with one handle that usually has a cover (WordNet). It is usually nicer than a pitcher.Return to place in story.

China

Xin-Yang Li 0000-0002-4858-2332; Gen Teng 0000-0002-2894-0964; Xing Zhao 0000-0003-3179-8775; Cui-Min Zhu 0000-0002-7366-5578.

So the servant brought out the three cloaks, and when the judges saw the grey one, which the Princess was in the habit of wearing, they said: Let it be embroidered19 with gold and silver; it shall be your wedding mantle

Gong ZM

A

Gong ZM

1 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016.

2016; 66: 7-30 [PMⅠD: 26742998 DOⅠ: 10.3322/caac.21332]

2 Bosman FT, Carnerio F, Hruban RH, Theise ND. WHO classification of tumors of the digestive system [M]. 4th ed. Lyon: ⅠARC Press, 2010: 134-136

3 Linardoutsos D, Frountzas M, Feakins RM, Patel NH, Simanskaite V, Patel H. Primary colonic squamous cell carcinoma: a case report and review of the literature.

2020; 102: e1-e7 [PMⅠD: 32538102 DOⅠ: 10.1308/rcsann.2020.0149]

4 Schmidtmann M. Zur kenntnis seltener Krebsformen.

1919; 226: 100-118 [DOⅠ: 10.1007/BF02039541]

5 Ozuner G, Aytac E, Gorgun E, Bennett A. Colorectal squamous cell carcinoma: a rare tumor with poor prognosis.

2015; 30: 127-130 [PMⅠD: 25392258 DOⅠ: 10.1007/s00384-014-2058-9]

6 Donato-Brown D, Antoniou A, Murphy J. Colorectal squamous cell carcinoma: A population-based study of rare tumor type.

2019; 6: e145

7 T?rcol SA, Ghidersa A, Negreanu L, Sajin M, Dumitru AV. Squamous metaplasia within a sigmoid adenoma. A rare feature.

2020; 61: 235-239 [PMⅠD: 32747915 DOⅠ: 10.47162/RJME.61.1.26]

8 Juturi JV, Francis B, Koontz PW, Wilkes JD. Squamous-cell carcinoma of the colon responsive to combination chemotherapy: report of two cases and review of the literature.

1999; 42: 102-109 [PMⅠD: 10211528 DOⅠ: 10.1007/BF02235191]

9 Dikshit V, Ali Ⅰ, Patil C, Manerikar K, Mody P. Squamous Cell Carcinoma of Colon-an Etiopathological Surprise.

2019; 50: 604-608 [PMⅠD: 29417382 DOⅠ: 10.1007/s12029-018-0072-9]

10 Wang XP, Du H, Li XB, Liu SS. Clinicopathologic analysis of primary colon adenosquamous carcinoma and squamous carcinoma.

2018; 49: 94-97

11 Landau D, Garrett C, Chodkiewicz C. A case of primary squamous cell colon cancer.

2007; 13: 47-48 [PMⅠD: 17621567 DOⅠ: 10.1177/1078155207072493]

12 Samo S, Sherid M, Liu K, Kia L, Elliott GJ. Basaloid Squamous Cell Carcinoma of the Sigmoid Colon.

2015; 2: 161-164 [PMⅠD: 26157950 DOⅠ: 10.14309/crj.2015.41]

13 Zhao S, Guo J, Sun L, Lv J, Qiu W. Gemcitabine-based chemotherapy in colon squamous cell carcinoma: A case report and literature review.

2017; 6: 561-565 [PMⅠD: 28413669 DOⅠ: 10.3892/mco.2017.1178]

14 Lu ZJ, Sun XW. A case of primary squamous colon carcinoma.

2016; 23: 978

15 Dong Y, Wang J, Ma H, Zhou H, Lu G, Zhou X. Primary adenosquamous carcinoma of the colon: report of five cases.

2009; 39: 619-623 [PMⅠD: 19562453 DOⅠ: 10.1007/s00595-008-3884-6]

16 Kang H, O'Connell JB, Leonardi MJ, Maggard MA, McGory ML, Ko CY. Rare tumors of the colon and rectum: a national review.

2007; 22: 183-189 [PMⅠD: 16845516 DOⅠ: 10.1007/s00384-006-0145-2]

17 Shao YF, Pan GL, Zhou CN, Yu HT. [Squamous cell carcinoma of the ascending colon--a case report and review of literature].

1987; 9: 315-316 [PMⅠD: 3315530]

18 Leung KK, Heitzman J, Madan A. Squamous cell carcinoma of the rectum 21 years after radiotherapy for cervical carcinoma.

2009; 15: 196-198 [PMⅠD: 19636183 DOⅠ: 10.4103/1319-3767.54745]

19 Pittella JE, Torres AV. Primary squamous-cell carcinoma of the cecum and ascending colon: report of a case and review of the literature.

1982; 25: 483-487 [PMⅠD: 7094788 DOⅠ: 10.1007/BF02553663]

20 Cheng H, Sitrin MD, Satchidanand SK, Novak JM. Colonic squamous cell carcinoma in ulcerative colitis: Report of a case and review of the literature.

2007; 21: 47-50 [PMⅠD: 17225882 DOⅠ: 10.1155/2007/904081]

21 Comer TP, Beahrs OH, Dockerty MB. Primary squamous cell carcinoma and adenocanthoma of the colon.

1971; 28: 1111-1117 [PMⅠD: 5125659 DOⅠ: 10.1002/1097-0142(1971)28:5<1111::aid-cncr2820280504>3.0.co;2-v]

22 Michelassi F, Mishlove LA, Stipa F, Block GE. Squamous-cell carcinoma of the colon. Experience at the University of Chicago, review of the literature, report of two cases.

1988; 31: 228-235 [PMⅠD: 3280272 DOⅠ: 10.1007/BF02552552]

23 Neumann H, Vieth M. Squamous cell carcinoma of the sigmoid colon arising on base of a nonpolypoid tubulovillous adenoma.

2014; 46 Suppl 1 UCTN: E455-E456 [PMⅠD: 25314191 DOⅠ: 10.1055/s-0034-1377493]

24 Cramer SF, Velasco ME, Whitlatch SP, Graney MF. Squamous differentiation in colorectal adenomas. Literature review, histogenesis, and clinical significance.

1986; 29: 87-91 [PMⅠD: 3943426 DOⅠ: 10.1007/BF02555383]

25 Gooneratne AT, James AO, Gupta J, Abdulaal Y. Squamous cell carcinoma arising in a mature cystic teratoma invading the sigmoid colon: a rare presentation.

2015; 2015 [PMⅠD: 25935913 DOⅠ: 10.1136/bcr-2014-208472]

26 Mondal SK. Primary squamous cell carcinoma of the cecum.

2009; 5: 328-330 [PMⅠD: 20160376 DOⅠ: 10.4103/0973-1482.59900]

27 Dyson T, Draganov PV. Squamous cell cancer of the rectum.

2009; 15: 4380-4386 [PMⅠD: 19764088 DOⅠ: 10.3748/wjg.15.4380]

28 Péron J, Bylicki O, Laude C, Martel-Lafay Ⅰ, Carrie C, Racadot S. Nonoperative management of squamous-cell carcinoma of the rectum.

2015; 58: 60-64 [PMⅠD: 25489695 DOⅠ: 10.1097/DCR.0000000000000218]

29 Musio D, De Felice F, Manfrida S, Balducci M, Meldolesi E, Gravina GL, Tombolini V, Valentini V. Squamous cell carcinoma of the rectum: The treatment paradigm.

2015; 41: 1054-1058 [PMⅠD: 25956212 DOⅠ: 10.1016/j.ejso.2015.03.239]