ASC is a malignant tumor that contains both glandular and squamous histologic components. According to the relationship between glandular and squamous ingredients, ASC can be classified into composite and collision types. Composite type refers to the mixed distribution of adenocarcinoma and squamous cell carcinoma, while collision type refers to the adenocarcinoma composition and squamous cancer composition has a clear boundary(7,8༌9). There are four hypotheses about the histogenesis of squamous cell carcinoma in colonic ASC patients: 1) Ectopic squamous cells of the colonic mucosa directly transform into squamous cell carcinoma; 2) basal cells transform into squamous cells; 3)Squamous metaplasia of glandular cells;4༉Squamous metaplasia of adenocarcinoma cells. At present, the fourth hypothesis is most accepted by scholars.
The common clinical manifestations of colon ASC patients are similar to that of colon ADC, including abdominal pain, weight loss, altered bowel habits, bloody stool. Noteworthy, hypercalcemia is occasionally encountered in patients with colon ASC(10、11、12). The cause of hypercalcemia in colon ASC patients is mainly due to the release of parathyroid hormone by tumor, it means that hypercalcemia appears as a paraneoplastic syndrome of ASC(10). Secondly, for patients with advanced ASC, bone metastasis can also cause elevated serum calcium(11).
Colon ASC is rare in clinical practice and thus the understanding and treatment experience about this disease is very limited. Therefore, no consensus on effective treatment for colon ASC has been reached. At present, the treatment of colon ASC is mainly referred to colon ADC, that is surgery plus adjuvant chemotherapy. Regarding postoperative chemotherapy of colon ASC, FOLFOX (consists of fluorouracil, folinic acid and oxaliplatin) regimen is mostly used(13, 14, 15).
In recent years, postoperative chemotherapy combined with targeted therapy or immunotherapy has been proposed. For patients with suitable genetic test results, postoperative chemotherapy combined with targeted therapy or immunotherapy can be tried, although the effects of these treatments are not yet clear. A study showed that patients with BRAF V600E colorectal cancer have a poor clinical response to FOLFOX chemotherapy plus bevacizumab, leading to poor prognosis(16). In the future, more clinical trials are needed to optimize the postoperative treatment regimen of ASC and determine the exact extent of its clinical benefits.
Several studies have shown that the prognosis of colon ASC is worse than that of colon ADC(17, 18, 19, 20). In 2020, Nasseri et al. conducted the largest retrospective cross-sectional examination of ASC from a national database for over 30 years. The mean age of patients in this study was approximately 64 years. The results showed the median overall survival for colon ASC patients was 13.9 months (95% CI: 10.98-16.83). For stage IV ASC and ADC of colon, the median overall survival was 14.1 months and 8.0 months(P༜0.0001), respectively(17). According to a study conducted by Frizelle et al, the prognosis of colorectal ASC is worse than that of ADC in stage III or IV, but similar to ADC in stage I or II. The 5-year survival rate for patients with stage I-III colorectal ASC was about 65%, while the median survival rate for patients with stage IV disease was 8.5 months(18).
The prognosis of ASC is worse than that of ADC, which may be due to: 1) Both adenocarcinoma and squamous cell carcinoma can metastasise, but the later appears to spread more easily and more aggressively than the former(21、22). 2) At the time of diagnosis, the incidence of distant metastasis (stage IV) of colon ASC was significantly higher than that of ADC(5, 17). The most common metastasis sites of colon squamous cancer are liver, peritoneum and lung in order(18).
In this case, no distant metastasis was found on preoperative examinations. After radical resection, pathological diagnosis of the sigmoid colon mass was stage ⅢB (pT3N1bM0) adenosquamous carcinoma. When adjuvant chemotherapy is about to be performed 4 weeks after surgery, the imaging examination revealed a liver mass, which was considered to be tumor metastasis. It can be seen that colonic ASC is awfully aggressive in adolescents. Then we performed percutaneous radiofrequency ablation of liver mass on this patient. XELOX chemotherapy was started after radiofrequency ablation, and the patient was well tolerated. However, re-examination showed recurrence of liver metastasis after the completion of 4 cycles of chemotherapy. Eventually, the patient and her family decided to give up further treatment and the girl died 8 months postoperatively.
In Choi’s report, a 43-year-old female underwented laparoscopic right colectomy. Pathological diagnosis of the colon specimen was stage IIIB (T3 N2a M0) adenosquamous carcinoma. The female patient received 6 cycles of FOLFOX4 (oxaliplatin, leucovorin, and fluorouracil) chemotherapy postoperative, and no tumor recurrence was found during the 10 months follow-up examinations since the completion of chemotherapy(13). Compared with the case reported by Choi, the outcomes of the girl in our report is quiet frustrsting. It’s not difficlut to draw the conclusion that cases with liver metastasis have an unfavorable prognosis for colon ASC patients. Besides, We speculate that the effect of FOLFOX chemotherapy regimen is superior or non-inferior to XELOX regimen in patients with colonic ASC.
Our medical team specially held a seminar on this case. The lessons we have learned from this case are as follows: 1) Colonic ASC can also occur in pediatrics. Therefore, do not ignore the possibility of colon ASC in adolescents with related symptoms. 2) For patients diagnosed with colon ASC, comprehensive examination must be performed to determine whether distant metastases have occurred. 3) After surgery, genetic testing of pathological tissue is required to determine if there is a suitable immunotherapy or targeted therapy. 4) During the treatment of colon ASC, the frequency of imaging examinations should be appropriately increased in order to detect changes in patients' condition in time. Then adjust to the most appropriate treatment in a timely manner.
Our team has two main expectations about future research on colon ASC. On one hand, lots of research on the etiology and tissue origin of colon adenosquamous carcinoma are needed. Only in this way can we understand this disease more clearly, and thus adopt more effective prevention and treatment methods. On the other hand, studies on postoperative adjuvant treatment of colon ASC patients in different age groups are also needed, so as to obtain a better prognosis as much as possible.
In conclusion, colon adenosquamous carcinoma is an exceedingly rare malignancy. To our knowledge, this is the first reported case of colon ASC in pediatrics. This case demonstrates the prognosis of this disease is poor, and colon ASC may even have worse prognosis in adolescents than in adults. For colon ASC patients, cases with liver metastasis have an awfully unfavorable prognosis. In order to achieve better outcomes, more research are needed to find out the histogenesis of ASC, and determine the best postoperative adjuvant treatment for colon ASC patients.