Floxuridine

* Metastatic, noncolorectal carcinoma involving the anal canal is exceptionally rare, with only 3 cases being described in the medical literature. We report the case of a 53-year-old man with an anal mass clinically presenting as a large, thrombosed, internal hemorrhoid. The patient had a history of nephrectomy for renal cell carcinoma 9 years previously. The resected anal lesion was histologically identical to the primary tumor in the kidney, showing features of renal cell carcinoma of the clear cell type. To the best of our knowledge, this is only the fourth reported case of metastatic, noncolorectal carcinoma involving the anal canal and is the first report of a renal cell carcinoma metastasis to this site.

(Arch Pathol Lab Med. 2002;126:856-858)

Hemorrhoidectomy specimens are common surgical pathology specimens that usually spark little interest in the examining pathologist. However, we report the case of a hemorrhoid that proved to be a fascinating lesson in the biology of neoplasia. This case also serves to remind pathologists of the importance of careful microscopic examination of all surgical specimens, even the routine ones.

REPORT OF A CASE

A 53-year-old man underwent surgical resection of a painful, bleeding, anal mass, which had been present for many months, necessitating the administration of multiple blood transfusions and intravenous narcotic analgesics for symptomatic relief. At surgery, the polypoid mass was delivered from the anus, clamped across its base, and excised above the clamp. The clinical impression was that of a large, thrombosed, internal hemorrhoid.

The patient's medical history was significant for stage IV renal cell carcinoma, diagnosed 9 years previously following radical nephrectomy. The primary tumor in the right kidney measured 19.5 x 14 x 10.5 cm, was confined to the Gerota fascia, and was not associated with lymph node metastasis. Histologically, the tumor was a Fuhrman nuclear grade 2 renal cell carcinoma of the clear cell type. In the first 4 years following nephrectomy, the patient underwent 2 pulmonary resection procedures to remove metastatic nodules from his lungs bilaterally. Six years after the nephrectomy, a partial duodenectomy was performed to control bleeding from a 3.0-cm metastasis that involved the second part of the duodenum. However, the duodenal lesion eventually recurred, attaining a maximum dimension of 7.0 cm as measured by computed tomography. Subsequent episodes of upper gastrointestinal tract bleeding were successfully managed by therapeutic embolization of the gastroduodenal artery. Two months before excision of the "hemorrhoid," open craniotomy was performed to resect a 1.3-cm metastasis from the left occipital lobe. This was followed by a course of whole brain irradiation to treat residual intracranial disease. In addition to surgery and radiotherapy, the patient received systemic therapy on multiple occasions throughout the 9-year duration of his illness. Individual agents included interferon, 5-fluorouracil, floxuridine, and thalidomide.

MATERIALS AND METHODS

The operative specimen was received fresh and photographed after slicing. Sections were fixed in 10% neutral-buffered formalin, embedded in paraffin, processed routinely, sectioned, and stained with hematoxylin-eosin. Clinical information was retrieved from the patient's medical chart.

PATHOLOGIC FINDINGS

The resection specimen consisted of a 5.0 x 3.5 x 3.5cm polypoid mass, covered by extensively ulcerated, pink-- white mucosa. The mass was solid and had a homogeneous, glassy, red cut surface (Figure 1). Microscopically, the lesion was partially covered by benign squamous mucosa (Figure 2) and contained multiple dilated venous channels, typical of hemorrhoidal tissue (Figures 2 and 3). However, the predominant pathologic finding was sheets and nests of polygonal tumor cells with clear cytoplasm and intermediate-grade nuclei, associated with a rich vascular network, consistent with metastatic renal cell carcinoma, clear cell type (Figure 4). Tumor extended to the resection margin of the specimen.

COMMENT

In general, metastatic tumors that involve the small intestine and colorectum are uncommon, with the most frequently contributing primary tumors being malignant melanoma, choriocarcinoma, and carcinomas of the lung, breast, kidney, and stomach.1 Metastatic tumor involvement of the anal canal is rare. A MEDLINE search of the medical literature identified only 3 documented cases of metastatic, noncolorectal carcinoma involving the anal canal. Ger and Reuben2 reported the case of a 49-year-old man who died within 48 hours of undergoing an abdominoperineal resection for biopsy-proven squamous cell carcinoma of the anal canal. At autopsy, a cavitating squamous cell carcinoma of the left upper lobe bronchus, associated with hematogenous metastasis to the left ventricular myocardium, was identified. Since the anal squamous cell carcinoma was histologically confined to the anorectal submucosa and included a prominent intravascular component, the authors' reasonable conclusion was that this lesion most likely represented a metastasis from the left lung primary tumor. Kanhouwa et a13 reported the case of a 45-year-old man with anaplastic carcinoma of the lung, who developed anal metastasis 2 months after initiation of radiotherapy. This patient died with disseminated metastatic disease 8 months after diagnosis. Dawson et al4 reported the case of a 70-year-old woman with lobular carcinoma of the breast, who developed obstructive anal stenosis 34 months following primary diagnosis. Biopsy of the stenosed anal canal reportedly demonstrated metastatic lobular carcinoma. Unfortunately, none of the pathologic findings in this case were illustrated in the published report. Finally, there is a textbook observations of a case of pancreatic carcinoma with spread to the anal canal, but this case was not formally published in the peer-reviewed medical literature.

In descending order of frequency, the most common sites of metastasis of renal cell carcinoma are the lung, lymph nodes, liver, bone, adrenal glands, kidney, brain, heart, spleen, intestine, and skin.6 Metastatic renal cell carcinoma involving the small intestine accounts for 7.1% of all metastatic tumors to this site.' Most often, metastasis of renal cell carcinoma to the intestines occurs in the face of metastatic involvement of multiple organs, as was the case in our patient. In one large autopsy series, of 1293 cases of renal cell carcinoma in which 1 or more metastases were identified, intestinal involvement was reported in just 9% of the cases and then only when 3 or more organ sites were involved.7 However, as demonstrated by several authors in the literature, the true incidence of tumor metastasis to the intestines is largely dependent on careful inspection of the bowel at autopsy and is likely to be significantly higher than reported.

The differential diagnosis of a clear cell neoplasm involving the anal canal includes metastatic carcinomas of the kidney and prostate and primary anal tumors such as malignant melanoma and the so-called clear cell carcinoma of the anal canal.8 Metastatic prostatic adenocarcinoma can be readily distinguished from renal cell carcinoma by the immunohistochemical positivity of tumor cells for prostate-specific antigen. Primary malignant melanoma, which rarely can be solely composed of clear cells, often contains a functional component and will be immunoreactive with markers such as S100 protein, HMB-45, and melan-A (MART-1). Clear cell carcinoma of the anal canal, a variant of anal transitional zone carcinoma, has been the subject of a single case report.8 As described by these authors, the morphologic features seen in their case were essentially those of a moderately differentiated, papillary adenocarcinoma containing columnar cells, approximately 50% of which possessed clear apical cytoplasm. The tumor cells were further characterized by positive immunostaining for carcinoembryonic antigen. In addition, tubulovillous adenomatous changes were present in the adjacent colorectal mucosa.8 None of these features can be considered typical of conventional clear cell carcinoma of the kidney.

Finally, although unusual, this case lends some support to the practice of routine histopathologic examination of hemorrhoidectomy specimens, especially since a diagnosis of malignancy was not clinically entertained. "Incidental" neoplasia is reportedly found in the tissues of 0.2% to 4.4% of patients undergoing minor surgery of the anal canal, including hemorrhoidectomy, anal fissurectomy, and anal fistulectomy.9 In most instances, the neoplastic lesion proves to be either an in situ or an early invasive squamous carcinoma, and the patient is effectively cured by hemorrhoidectomy.9 Rare cases of incidentally discovered anal adenocarcinoma have also been reported.10 Nevertheless, the cost-effectiveness of routine histologic examination of hemorrhoidectomy specimens continues to be widely debated. Some advocate careful anorectal examination before hemorrhoidectomy, with visual and manual inspection of any excised tissue by the surgeon, reserving histopathologic examination for suspicious lesions only.10,11 However, in our case, the possibility of metastatic renal cell carcinoma was not clinically entertained despite the presence of widespread metastases in other organs. Therefore, it is doubtful that gross inspection of the present "hemorrhoid" would have triggered any suspicions. This example of metastatic renal cell carcinoma, disguised as a thrombosed internal hemorrhoid, adds a new dimension to the notorious reputation of renal cell carcinoma as being one of the great mimics of clinical medicine.

References

1. Willis RA. Secondary tumors of the intestines. In: The Spread of Tumours in the Human Body. 3rd ed. London, England: Butterworth & Co Ltd; 1973:209215.

2. Ger R, Reuben J. Squamous-cell carcinoma of the anal canal: a metastatic lesion. Dis Colon Rectum. 1968;11:213-219.

3. Kanhouwa S, Burns W, Matthews M, et al Anaplastic carcinoma of the lung with metastasis to the anus: report of a case. Dis Colon Rectum. 1975;18:42-48.

4. Dawson PM, Hershman MJ, Wood CB. Metastatic carcinoma of the breast in the anal canal. Postgrad Med J. 1985;61;1081.

5. Fenger C. Surgical pathology of the anal canal: a review of the recent literature on the anatomy and pathology. In: Fenoglio-Preiser CM, Wolff M, Rilke F, eds. Progress in Surgical Pathology. Berlin, Germany: Springer-Verlag; 1989: 237-260.

6. Murphy WM, Beckwith JB, Farrow GM. Tumors of the Kidney, Bladder, and Related Urinary Structures. Washington, DC: Armed Forces Institute of Pathology; 1994:128. Atlas of Tumor Pathology; 3rd series, fascicle 11.

7. Saitoh H. Distant metastasis of renal adenocarcinoma. Cancer. 1981;48: 1487-1491.

8. Watson PH. Clear-cell carcinoma of the anal canal: a variant of anal transitional zone carcinoma. Hum Pathol. 1990;21:350-352.

9. Foust RL, Dean PJ, Stoler MH, et al. Intraepithelial neoplasia of the anal canal in hemorrhoidal tissue: a study of 19 cases. Hum Pathol. 1991;22:528534.

10. Timaran CH, Sangwan YP, Solla IA. Adenocarcinoma in a hemorrhoidectomy specimen: case report and review of the literature. Am Surg. 2000;66:789792.

11. Cataldo PA, MacKeigan JM. The necessity of routine pathologic evaluation of hemorrhoidectomy specimens. Surg Gynecol Obstet. 1992;174:302-304.

Ravindranauth N. Sawh, MBBS, DM; Joanna Borkowski, MD; Russell Broaddus, MD, PhD

Accepted for publication October 29, 2001.

From the Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Tex.

Reprints: Russell Broaddus, MD, PhD, Department of Pathology, Box 85, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (e-mail: rbroaddu@mdanderson.org).

Copyright College of American Pathologists Jul 2002
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