Cancer lesions liver

A 44-year-old woman presented with progressive weakness and fatigue of several weeks' duration, decreased appetite, nausea without vomiting, and a more than 20-lb weight loss. Colonoscopy revealed a soft, delicate, villous mass 14 cm from the anal verge. A biopsy specimen revealed a tubulovillous adenoma. Further workup revealed numerous hypodense areas in the liver and a solitary lesion in the left iliac bone. There was a nonobstructive, circumferential mass in the sigmoid colon. Computed tomography-guided biopsy of the bone lesion produced a specimen that revealed a poorly differentiated small cell carcinoma with neuroendocrine features that was positive for synaptophysin, keratin CAM 5.2, and keratin AEl /3 but negative for chromogranin, leukocyte common antigen/CD45, and vimentin. The patient's symptoms worsened, and a laparoscopic, hand-assisted anterior resection of the rectosigmoid colon and liver biopsy was performed. The resected bowel measured 26 cm in length with gross distortion by a large tumor that extended out to the serosa (Figure, A). The opened colon revealed a 6.5-cm mass that involved 80% of the bowel. There was a distinct villous appearance to the upper half of the neoplasm and a solid appearance to the lower half, readily apparent on low-power microscopic examination (Figure, B). There were 2 histologically distinct tumors: a classic tubulovillous adenoma without evidence of malignant transformation in the luminal half and a high-grade small cell carcinoma below the adenoma, invading through the muscular layer and out to the serosa. The 2 tumors were sharply demarcated from each other (Figure, C). Immunohistochemical studies on the colon tumor were similar in the small cell component to that of the small cell neoplasm aspirated from the bone lesion. Synaptophysin staining was strongly positive, confirming neuroendocrine derivation (Figure, D). Lymphovascular invasion was present, and 6 of 31 lymph nodes were positive. The liver biopsy specimen revealed a small cell carcinoma also with neuroendocrine features. The neoplasm was classified as T3 N2 M1 or stage IV cancer.

What is your diagnosis?

Pathologic Diagnosis: Small Cell (Neuroendocrine) Carcinoma of the Colon With Metastasis and an Associated, Overlying Villous Adenoma

Small cell carcinomas from any site are aggressive tumors that often present in the advanced stage, usually with distant metastasis. The prognosis is generally poor. However, recent chemotherapeutic regimens have demonstrated reasonable efficacy against small cell carcinomas, with increased survival and, in some instances, cure.

Small cell carcinoma of the colon was described more than 40 years ago.1 In 1978, Gould and Chejfec2 presented 4 cases of neuroendocrine carcinoma of the colon with biochemical and ultrastructural analysis. They showed that these histologically undifferentiated neoplasms possessed neuroendocrine characteristics by identification of neurosecretory granules and biochemical expression of vanillylmandelic acid and catecholamines. Their findings confirmed an association of these tumors with the then recently described amine precursor uptake and decarboxylase system. They speculated that these tumors were likely of neuroectodermal derivation. In 1983, Mills and coworkers3 described a series of similar small cell undifferentiated carcinomas of the colon, but this time most of the tumors they described were seen in association with overlying colonie adenomas. In their article, 4 of 5 cases were found to have villous or tubulovillous adenomas adjacent to the highly anaplastic carcinomas but with no obvious transition. The fifth patient had a history of an adenoma elsewhere in the bowel. They believed that this finding, the first such reported association, was in support of the theory that neoplastic stem cells in the colon were capable of divergent differentiation, in this case growing in one direction as an anaplastic small cell carcinoma and in the other direction as a dysplastic colonie polyp. Furthermore, they suggested that such neuroendocrine carcinomas might be of endodermal rather than neuroectodermal derivation. Since then, there have been a number of reports of small cell carcinomas of the large bowel with or without associated adenomas.4-7 These reports confirm these are highly malignant neoplasms that behave as aggressively as small cell neoplasms from other organs. Usually, they have metastasized by the time of diagnosis, most to the liver and/or bone, and patients typically die within a matter of months.5,7 Some of the early cases were identified during postmortem examination. Although a significant proportion of these tumors present in the right colon, they may be seen anywhere in the large bowel.4

The histologie diagnosis of small cell carcinoma of the colon is usually not difficult, provided diagnostic material is available. Macroscopically, these can be large, bulky neoplasms that protrude prominently from the serosa and may, at times, give the impression of an extracolonic neoplasm.6 Microscopically, hematoxylin-eosin staining reveals characteristically small blue cell tumors that grow predominantly in a solid pattern. They have highly anaplastic cellular features with brisk mitoses, ulceration, necrosis, lymphovascular invasion, and lymph node involvement. Liver metastasis is frequent at initial diagnosis, and was present in more than 70% of cases in one series.4 Bony metastasis is also often seen.5,6 The overall prognosis is poor, and survival is similar to that of small cell carcinomas elsewhere and usually worse than typical adenocarcinomas of the colon.7 The association of small cell carcinomas with tubulovillous and villous adenomas has been well established but can present a diagnostic dilemma. As in the present case, the colonoscopic biopsy specimen was superficial and only revealed a tubulovillous adenoma without any evidence of a malignant component. It was because of other systemic symptoms that a more extensive workup was performed, ultimately revealing lesions in the liver and skeletal system. When a biopsy of the bone lesion was performed, there was no immediate thought of an association with the lesion in the colon. It was only when the entire large bowel tumor was resected that the association became evident. Another potential pitfall is the possibility of misdiagnosis if the specimen is not adequate or if correct ancillary studies are not performed.6 The differential of any small cell tumor should always include small cell carcinoma, lymphoproliferative disorders, and round cell tumors. Knowing that there is an association between villous adenomas and small cell carcinomas can serve as a clue to pathologists to be on the lookout for this unusual neoplasm. The usefulness of immunohistochemical analysis is obvious in this type of case but has limitations. Although helpful in distinguishing lymphoma from carcinoma from a round cell tumor, it is not helpful in pinpointing the site of origin of the neoplasm. This becomes especially important when there is limited biopsy material from a distant metastasis that shows a small cell carcinoma and a colonie biopsy specimen that reveals a villous adenoma. Awareness of the association can help the physician arrive at a correct diagnosis, facilitating timely and proper therapy. Although the prognosis is poor, recent advances have shown success with certain adjuvant therapeutic modalities.8 The treatment for small cell carcinomas is different from that for colonie adenocarcinomas of a similar stage. Therefore, the importance of an accurate diagnosis is underscored. Although there has been debate regarding tumor histogenesis, a multipotential stem cell of endodermal lineage is likely the cell of origin in these tumors.

References

1. Cleary AP, Dockerty MB, Waugh JM. Small cell carcinoma of the colon and rectum. Arch Surg. 1961:83:164-172.

2. Could VE, Chejfec C. Neuroendocrine carcinomas of the colon. Am J Surg Pathol. 1978;2:31-38.

3. Mills SE, Alien MS Jr, Cohen AR. Small-cell undifferentiated carcinoma of the colon: a clinicopathologic study of 5 cases and their association with colonie adenomas. Am J Surg Pathol. 1983:7:643-651.

4. Burke AB, Shekitka KM, Sobin LH. Small cell carcinomas of the large intestine. AmJ CUn Pathol. 1991:95:315-321.

5. Gaffey MJ, Mills SE, Lack EE. Neuroendocrine carcinoma of the colon and rectum. Am 1 Surg Pathol. 1990;14:1010-1023.

6. Petros JG, Tsoukas A, Chong FK. Small cell carcinoma of the colon presenting as a mass in the colonie mesentery. J Clin Gastroenterol. 1993:2:175-177.

7. Sacralides TJ, Szeluga D, Staren ED. Neuroendocrine cancers of the colon and rectum: results of a 10-year experience. Dis Colon Rectum. 1994;37:635-642.

8. Lo Re G, Canzonieri V, Veronesi A, et al. Extrapulmonary small cell carcinoma: a single-institution experience and review of the literature. Ann Oncol. 1994:5:909-913.

Christina Ispas, MD; Jeanne Yu, MD; Debra R. Tarantino, MD; Jonathan F. Lara, MD