Metastasis of Rectal Signet Ring Cell Carcinoma to Typical Lipoma: A Rare Presentation of the Tumor-to-Tumor Metastasis Phenomenon

Abstract

Rectal signet ring cell carcinoma represents a rare subtype of colorectal adenocarcinoma known for its aggressive biological nature and poor prognosis. Although the co-occurrence of colorectal carcinoma with other tumors has been reported, the uncommon phenomenon of tumor-to-tumor metastasis, first described in 1930, remains rare. The most frequent donor neoplasms are lung or breast carcinomas, whereas cerebral meningiomas have been reported to be the most frequent recipient neoplasms. Here we report a case of a typical lipomatous tumor harboring metastatic signet ring cell rectal carcinoma. It is about a 42-year-old man diagnosed with rectal signet ring cell carcinoma and treated with concurrent radiotherapy and chemotherapy followed by an anterior resection and manual coloanal anastomosis with a temporary ileostomy. During the surgery, an abdominal wall lipoma was discovered and excised. A histopathological examination revealed infiltration of the fibro adipose tissue by a mucinous adenocarcinoma with a contingent of signet ring cells. The patient died 12 months after adjuvant chemotherapy due to peritoneal progression. To the best of our understanding, this represents the initial documented instance of tumor-to-tumor metastasis from rectal signet cell carcinoma to a conventional nonvascular lipoma. Consequently, even if one of these tumors appears clinically and radiologically benign, it is prudent to entertain the prospect of tumor-to-tumor metastasis. Thus, a comprehensive pathologic study of both tumors is highly recommended.

Introduction

Colorectal cancer (CRC) is the world’s third most frequent cancer and the fourth leading cause of cancer mortality. ¹ Signet ring cell carcinoma (SRCC) is a rare histological form of rectal cancer, accounting for less than 1% of CRCs and about 1.39% of rectal cancers. ² It is typically aggressive and has a poor prognosis. It most frequently metastases to the liver, lung, and central nervous system. ³ However, metastases from CRC to another benign or malignant tumor, recognized as the phenomenon of “tumor-to-tumor metastasis,” are exceedingly uncommon. It represents a sign of poor prognosis and reflects the dissemination of the disease. ⁴ Herein, we present a case of a colorectal signet cell carcinoma with the fortuitous discovery of a metastatic localization within a resected lipoma of the anterior abdominal wall. To the best of our knowledge, this represents the inaugural instance documented in the literature involving this specific pairing of a donor and a host tumor, and marks the initial occurrence of metastasis in a typical lipoma.

Case Report

A 42-year-old man, previously without any medical history, started complaining of sudden intermittent bloody stools, weight loss, and diarrhea. Despite these symptoms, he did not seek medical attention elsewhere until 6 months later, when he was referred to our center for evaluation.

The physical exam revealed stable vital signs with generalized skin and conjunctival pallor and examination of the rectum revealed an indurated, circumferentially fixed and partially obstructive mass located 7 cm from the anal margin.

A colonoscopy was performed; revealing an ulcer-budding stenotic tumor of the middle rectum located 7 cm from the anal margin. Several biopsies were taken during the procedure. The histological analysis revealed signet ring cell adenocarcinoma. Given this finding, we conducted an esophago-gastro-duodenoscopy with biopsies, which uncovered no signs of malignancy.

The abdominopelvic magnetic resonance imaging (MRI) revealed an infiltrating and budding thickening of the mid-rectum measuring 70 mm in height and 16 mm in maximum thickness. The process appeared heterogeneous with hypointensity on T1, moderate hyperintensity on T2, and heterogeneous enhancement with infiltration of the rectal wall, mesorectal fat, and the right posterior rectal fascia associated with multiple mesorectal lymph nodes. The thoraco-abdominal computed tomography (CT) scan showed no evidence of metastatic lesions and the tumor was staged as T3d N2 M0. Laboratory tests showed anemia at 9 g/dl, normal levels of leukocytes and platelets, normal renal and hepatic function, and normal carcinoembrionary antigen level of 1.28 IU/L (normal range: 0-2.5 IU/L).

The patient presented 1 week later with symptoms of acute intestinal obstruction, for which he underwent a diverting colostomy. Then, he was started on concurrent chemoradiotherapy, receiving a total dose of 45 Gy, divided into 30 sessions with oral xeloda-based chemotherapy. During the restaging workup, the MRI revealed a partial response. After multidisciplinary consensus, a protected anterior resection was agreed upon.

Peroperative findings revealed a supraumbilical subcutaneous parietal well-limited lipoma of 8 cm of greatest dimension, which was resected.

He underwent an anterior resection and manual coloanal anastomosis with a temporary ileostomy. The surgical procedure was carried out uneventfully. The patient was discharged on the seventh postoperative day.

The histopathological examination of the anterior resection specimen reveals an ulcerated and infiltrative tumor on the right anterolateral wall of the rectum, measuring 35*15 mm. Microscopic examination concluded that the residual tumor is classified as grade 2 according to the Dworak classification (presence of fibrous or mucinous remodeling with a few persistent cells or glands). The remnant tumor cells infiltrate the wall down to the perirectal fat with a clearance of less than 1 mm. There was no evidence of lymphovascular or perineural invasion. Two metastatic lymph nodes out of 11 nodes sampled were identified.

The adipose mass weighs 60 g and measures 80*65*30 mm. At cut section, poorly defined fibrous areas were identified and well-sampled. Microscopic study revealed infiltration by a mucinous adenocarcinoma with a contingent of signet ring cells (Figures 1 and 2).

Figure 1.

Fibrous area (arrow) showing metastatic carcinoma cells infiltrating the lipoma from the rectal carcinomatous cells (H&E stain, ×4).

Figure 2.

(a) Neoplastic cells (circle) are isolated or arranged in small aggregates accompanied by marked desmoplasia (H&E stain, ×200). (b) Signet ring cells (arrow) are characterized by a central, optically clear, globoid droplet of cytoplasmic mucin with an eccentrically placed nucleus (H&E stain, ×400).

The disease was staged as ypT4N1M1 according to the Union for International Cancer Control (UICC) tumor node metastasis (TNM) staging classification. The patient was referred to the oncology department. He started adjuvant chemotherapy with FOLFOX-6 regimen (fluorouracil + leucovorin + oxaliplatin). A body CT scan during treatment revealed disseminated disease with diffuse peritoneal carcinomatosis. The patient received corticosteroid therapy and was proposed for second-line chemotherapy, but unfortunately, he passed away 12 months later.

Discussion

We presented a very unusual case of tumor-to-tumor metastases from a signet ring cell rectal carcinoma (RSRCC) metastasizing to an anterior abdominal wall intermuscular lipoma.

Metastasis is typically acknowledged to depend on the dynamic interaction between metastatic tumor cells and the microenvironment of the specific target organ. ⁵ The tumor-to-tumor metastatic rare phenomena was initially identified in 1930. ⁶ Campbell et al, ⁷ in 1968, defined 4 criteria for the diagnosis of this condition: (1) the presence of two or more distinct primary tumors; (2) the recipient tumor must be a true neoplasm; (3) the metastatic neoplasm is a true metastasis with established growth in the recipient tumor and is not the result of embolization or contiguous growth; and (4) metastasis to lymphatic tissue already involved by lymphoreticular tumors is excluded. Tumors developed within another tumor should be distinguished from collision, which refers to the growth of two different adjacent primary tumors due to their anatomical proximity. In addition, there are cases of multiple primitive malignant tumors, which involve the presence of more than two primary tumors in different organs or two tumors developing from different types of cells within the same organ. ⁸

To date, 150 cases of tumor-to-tumor metastasis have been documented in global studies. ⁸ The predominant donor neoplasms have originated from the breast, followed by the lung and kidney. ⁶ Colorectal rectal cancer, as observed in our case, is relatively uncommon as a donor tumor in this context of metastasis. Mizutani reported a case of a metastasis from a colon carcinoma to an intracranial oligodendroglioma. The radiological assessment posed challenges in detecting the metastatic involvement of colon carcinoma in the oligodendroglioma. Subsequently, a craniotomy was performed, and histologically, the tumor was diagnosed as a moderately differentiated adenocarcinoma and oligodendroglioma. ⁹ In 2020, Fahoum described a case of an 80-year-old woman diagnosed with an adenocarcinoma of the rectosigmoid colon and associated with a right ovarian cyst. The patient underwent a prophylactic bilateral salpingo-oophorectomy in addition to colectomy and immunohistochemical studies confirmed the diagnosis of metastatic colorectal adenocarcinoma to an ovarian cystadenofibroma. ¹⁰ In 2021, Krsteska reported a case of a 66-year-old Macedonian man with rectal SRCC of rectum metastasizing to synchronous renal cell carcinoma and to the adrenal gland and treated with a left nephrectomy and anterior rectal resection. ⁴

To our current understanding, this case represents the first documented instance of metastasis of rectal SRCC to a typical lipoma of the anterior abdominal wall.

The recipient can be either a benign or malignant tumor, more frequently a benign one, as documented in the Richardson and Katayama review. ¹¹ Thus, meningiomas have been identified as the most common benign neoplasm to develop metastases^12,13 followed by uterine leiomyoma, with 19 cases reported, including 18 cases of leiomyoma and one of lipoleiomyoma ⁶ and renal cell carcinoma representing the most common reported malignant tumor recipient. ¹⁰ Although the precise process or mechanism of tumor-to-tumor metastasis remains unclear, some authors suggested that high tumor vascularity from both donors and recipients is crucial to tumor spread. In addition, a slow-growing tumor, rich in lipids or collagen, may provide a favorable environment for the growth of a donor tumor.^7,13,14

Our case presented metastasis in typical lipoma of primary RSRCC at initial diagnosis. Lipoma is the most common soft-tissue tumor. It mainly affects middle-aged men and usually develops in the subcutaneous, intramuscular, or intermuscular areas. It is made up histologically of fat cells that are uniformly sized and well-differentiated. ¹⁵ According to previous studies, a typical lipomatous tumor is uncommon as a recipient due to its poor vascularity and low incidence of excision. However, hibernoma, ¹⁶ angiolipoma, ¹⁷ and myxoid liposarcoma ¹⁸ are a few additional recipient lipomatous tumors that have been reported in a few case reports. To the best of our knowledge, the first documented case of a tumor metastasizing to a typical lipoma was described by Nomura et al ¹⁹ and the corresponding donor was a gastric SRCC metastasizing to neck lipoma. In our report, we present the first documented case of SRCC metastasizing to a typical, nonvascularized lipoma.

Atypical density or signal characteristics in imaging investigations, such as CT and MRI, contrasted to those of the recipient tumor, may point to the existence of another tumor. Since tumor-to-tumor metastasis lacks clear imaging characteristics, it might be challenging to diagnose a metastatic tumor, mainly if the recipient tumor exhibits inhomogeneous features.^19,20 As imaging techniques are insufficient for the early detection of metastasis; histopathological and immunohistochemical studies are required for confirmation. ²¹ Typically, the donor tumor is discovered before the recipient tumor’s metastatic lesion and the detection of the metastatic lesion before identifying the donor tumor was documented in only 10% of cases. ¹⁹ Hence, when a patient with a malignant tumor exhibits a new tumor displaying irregularities, it is essential to consider the potential for tumor-to-tumor metastasis. ¹⁴ The fortuitous discovery of simultaneous lesions, as we noted in our case, is even rarer.

Evidence on long-term follow-up data and management is limited and ambiguous and the prognosis is considered poorer. Awareness of this condition is crucial as it influences the disease stage and therapy method. In addition, tumor-to-tumor metastasis cases can provide insight into the particular environmental factors that favor metastatic development.

Conclusion

Our case emphasizes the importance of considering tumor-to-tumor metastasis as a possibility, despite its rarity. The scarcity of similar reported cases underscores the need for additional research into advanced imaging techniques for metastasis detection and innovative therapeutic approaches.