Less Common Tumors and Tumorlike Lesions of the Colon, Rectum, and Anus



Less Common Tumors and Tumorlike Lesions of the Colon, Rectum, and Anus


Michael H. Polcino

Marvin L. Corman



To pathology we owe the realization that the contrast between health and disease is not to be sought in a fundamental difference of two kinds of life, nor in an alteration of essence, but only in an alteration of conditions.

—RUDOLF VIRCHOW: Disease, Life, and Man

Although adenoma and adenocarcinoma constitute the most commonly seen neoplasms of the colon, rectum, and anus, many other tumors and tumorlike conditions in this anatomic region have been described.514 Of these, some represent extraordinarily rare lesions and may thus be the source of difficult decisions in the therapeutic approach to the patient. Others are important because they represent benign conditions that may be mistaken for malignant processes. Many lesions present a similar clinical picture despite their diverse pathologic natures. Understanding the biology of each is vital to sound therapeutic intervention. The importance of adequate pathologic examination, therefore, cannot be overstressed.

The following classification scheme organizes diseases essentially by their tissue of origin.


▶ CLASSIFICATION OF UNUSUAL TUMORS AND TUMORLIKE CONDITIONS



















































Tumors of Epithelial Origin


Neuroendocrine carcinoma


Carcinoid tumor


Bowen’s disease


Perianal Paget’s disease


Basal cell carcinoma


Cloacogenic carcinoma


Malignant melanoma


Squamous cell carcinoma


Adenosquamous carcinoma or adenoacanthoma


Stem cell carcinoma


Tumors of Lymphoid Origin


Lymphoid hyperplasia, benign lymphoma, and lymphoid polyp


Malignant lymphoma


Extramedullary plasmacytoma


Mesenchymal Tumors


Fibrous tissue origin



Fibroma


Inflammatory fibroid polyp or eosinophilic granuloma


Fibrosarcoma


Malignant fibrous histiocytoma


Stromal origin



Gastrointestinal stromal tumors


Smooth muscle origin



Colonic leiomyoma


Rectal leiomyoma


Leiomyosarcoma


Rhabdomyosarcoma


Adipose tissue origin



Lipoma


Lipomatosis


Tumors of Neural Origin


Neurofibroma


Ganglioneuromatosis


Neurilemoma or schwannoma


Granular cell tumor


Vascular Lesions


Hemangioma


Lymphangioma


Hemangiopericytoma


Malignant vascular tumors (angiosarcoma, Kaposi’s sarcoma)


Heterotopias and Hamartomas


Endometriosis


Perineal endometrioma


Hamartoma


Retrorectal (presacral) cysts (developmental cysts, including dermoid cyst, epidermoid cyst, tailgut cyst, enteric cyst, rectal duplication, neurenteric cyst, and teratoma)


Colitis cystica profunda or enterogenous cysts


Ectopic tissue


Exogenous, Extrinsic, and Miscellaneous Conditions


Extraskeletal osteosarcoma


Choriocarcinoma


Metastatic tumor


Barium granuloma


Oleoma, eleoma, oil granuloma, and paraffinoma


Sarcoidosis


Wegener’s granulomatosis


Amyloidosis


Amyloid tumor


Malacoplakia


Sacrococcygeal chordoma


Ependymoma


Extramedullary (extraadrenal myelolipoma or angiomyelolipoma)


Anterior sacral meningocele


Extramedullary hematopoiesis


Pneumatosis cystoides intestinalis or pneumatosis coli


Duplication



▶ TUMORS OF EPITHELIAL ORIGIN


Neuroendocrine Carcinoma

Colorectal neuroendocrine (NE) tumors are classified as either low-grade carcinoid tumors or high-grade neuroendocrine carcinomas.54 This type of NE malignancy is usually found in the lung (oat cell carcinoma, small cell carcinoma), but it has on occasion been reported in extrapulmonary sites, including the colon and rectum.93,422,463 The so-called NE system includes endocrine cells distributed throughout the gastrointestinal (GI) tract, pancreas, lung, thyroid, adrenal gland, skin, and elsewhere, with intestinal NE cells being the largest component. Staren and colleagues defined NE carcinoma as a malignant epithelial neoplasm of predominantly NE differentiation and reserved the term carcinoid for their benign or very low-grade malignant counterparts (see the following section).478 The recognition that a neuroendocrine neoplasm is high grade (as opposed to a well-differentiated neuroendocrine neoplasm, such as a carcinoid tumor) is reasonably well standardized, with a mitotic cutoff of 10 per 10 high power fields (HPFs). This concept is widely used to separate these two groups, irrespective of the organ of origin.455 Neoplastic proliferation of these cells occurs primarily in the appendix, ileum, and rectum, although tumors occur at other sites as well.432 NE carcinomas can be further divided into small cell carcinoma and large cell carcinoma.455 A case of presacral NE carcinoma arising in a tailgut cyst has been reported.361 Another NE tumor, the very rare Merkel cell carcinoma, has been described in the anal canal.390


Associated Concerns

It is important to remember that there are certain colorectal manifestations of endocrine diseases that are not primary to the GI tract. Symptoms such as constipation are frequently observed in diabetic patients. Unexplained diarrhea should alert the clinician to the possibility of a pancreatic endocrine tumor.453 Furthermore, thyroid disorders may be associated with refractory constipation, diarrhea, or steatorrhea, and hyperparathyroidism often presents with constipation.453 In short, endocrine diseases can and often do present or are associated with intestinal symptoms.




Carcinoid Tumor

Carcinoids are slow-growing tumors of neuroectodermal origin that belong to the amine precursor uptake and decarboxylation system (APUD). They are the most common of the NE neoplasms of the GI tract. APUD cells constitute a group of apparently unrelated endocrine cells, which were named by the scientist A.G.E. Pearse, who developed the APUD concept in the early 1960s. These cells share the common function of secreting a low-molecular-weight polypeptide hormone. There are several different types that secrete the hormones secretin, cholecystokinin, and several others. Lubarsch, in 1888, was the first to describe a clinical case of carcinoid disease.313 The term Karzinoid, meaning carcinoma-like, was introduced by Oberndorfer in 1907.374 It was believed that the tumor was similar to carcinoma because metastases could develop, but the clinical course often tended to be relatively benign. Although carcinoids occur most commonly as primary tumors of the GI tract, they can also be found in such diverse locations as the bronchus, ovary, and kidney.

Carcinoids arise from Kulchitsky’s or basogranular enterochromaffin cells located in the crypts of Lieberkühn (Figure 26-1). A report of a patient with multiple carcinoid tumors of the rectum demonstrated numerous proliferations of extraglandular endocrine cells with no increase in intraglandular cell production.329 In the past few decades, numerous investigators have suggested that the histochemical, chemical, and clinical characteristics vary depending on the site of origin.58,383,540


Classification and Diagnosis

The current classification relates to both the anatomic site of the tumor and the reactivity to silver incorporation by cytoplasmic granules.62 A positive argentaffin reaction (argentaffinity) involves the reduction of silver salts to metallic silver by strong endogenous reducing substances.499 Argentaffinity usually implies that the argyrophil reaction will be positive, but the mechanism for the latter reaction is unknown.499 A positive argyrophil reaction occurs when metallic silver added in solution is precipitated on the cytoplasmic granules of the carcinoid cells. Two distinctive types of neurosecretory granules have been observed by electron microscopy.556 A relatively small granule appears to be associated with argyrophil carcinoids and a larger one with argentaffin (Figure 26-2).






FIGURE 26-1. Normal bowel showing dark-staining argyrophilic granules (in Kulchitsky cells) from which carcinoid tumors arise. (Original magnification × 600; courtesy of Rudolf Garret, MD.)

Midgut carcinoids (mid-duodenum to mid-transverse colon) are usually both argyrophil and argentaffin positive, are frequently multicentric in origin, and often are associated with the carcinoid syndrome. The syndrome is characterized by a complex of symptoms thought to be related to overproduction of serotonin (5-hydroxytryptamine), but fewer than 10% of all patients with carcinoid tumors exhibit this manifestation. Hindgut carcinoids have been reported to be rarely
argyrophil or argentaffin positive, are usually unicentric, and are not associated with the carcinoid syndrome.383 Saegesser and Gross, however, reported the carcinoid syndrome in an individual with carcinoid of the rectum, and Taxy and associates noted, in 23 patients, that most rectal carcinoids are argyrophilic if the more sensitive Grimelius method is employed.433,499 In this same group of patients, only three were argentaffin positive. The authors concluded that the Grimelius argyrophil stain is the most accurate light-microscopic means for confirming the diagnosis of a rectal carcinoid.







FIGURE 26-2. Carcinoid tumor showing argyrophilic granules in the cytoplasm. (Fontana stain; original magnification × 600; courtesy of Rudolf Garret, MD.)

Determination of urine 5-hydroxyindoleacetic acid (5-HIAA) excretion is not helpful in defining metastatic disease in rectal tumors because hindgut lesions are generally argentaffin negative and do not produce a detectable increase in tryptophan metabolites.58 Table 26-1 summarizes the classic differences between carcinoids based on gut location.








TABLE 26-1 Classic Differences among Foregut, Midgut, and Hindgut Carcinoids




































Foregut


Midgut


Hindgut


Location


Lungs, stomach, first part of duodenum


Duodenum through right colon, appendix


Transverse or left colon, rectum


Staining


Nonargentaffin but argyrophilic


Argentaffin + argyrophilic


Nonargentaffin but argyrophilic


Bioactivity


5-Hydroxytryptophan, ACTH, tachykinins, neurotensin, HCG; gastrin; low 5-HT content; high MAO activity without DAO activity


5-HT, tachykinins, rarely ACTH or 5-hydroxytryptophan; lower MAO activity than foregut carcinoids but higher DAO activity


Low 5-HT or ACTH content; may secrete somatostatin, tachykinins, glicentin, PYY, 5-hydroxytryptophan, neurotensin, pancreatic polypeptide, dopamine


Metastasis


25%, particularly to bone; metastases not required for systemic symptoms


60%-80% (proportional to tumor size) to liver; rarely to bone


5%-40% to bone


Presentation


Pulmonary obstruction, atypical neurohumoral symptoms


Bowel obstruction, classic carcinoid syndrome (diarrhea and flushing) if metastatic


Usually discovered by chance; rarely cause humoral symptoms


ACTH, adrenocorticotropic hormone; DAO, diamine oxidase; HCG, human chorionic gonadotropin; 5-HT, serotonin; MAO, monoamine oxidase; PYY, peptide YY. From Basson MD, Ahlman H, Wangberg B, et al. Biology and management of the midgut carcinoid. Am J Surg. 1993;165(2):288-297, with permission.



Incidence, Distribution, and Associated Conditions

The incidence of GI carcinoid tumors increases from duodenum to ileum, with more than 80% located in the distal small bowel. They arise most commonly in the appendix and are found in 0.26% of appendectomy specimens.84 The next most common location is the small intestine, followed by the rectum and stomach. Colonic involvement is infrequent, comprising 2.5% of GI carcinoids.84 Orloff collected 3,000 cases of such carcinoids from the literature and noted 38 patients with rectal tumors.383 Morson reported only 21 cases of rectal carcinoids seen at St. Mark’s Hospital in London in 25 years.359

In a collective review, Neary and colleagues analyzed the results of a number of studies.366 For example, in the United Kingdom, an incidence of 0.7 per 100,000 population was found. This is consistent with other reports from both the United States and Spain.

Modlin and associates evaluated 10,878 carcinoid tumors that were identified by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI) from 1973 to 1999 in addition to 2,837 carcinoid tumors that were registered previously by two earlier NCI programs.351 Two-thirds were found in the GI tract and about 25% in the bronchopulmonary system. The following was the distribution within the GI tract:



  • Small intestine (41.8%)


  • Gastric (20.5%)


  • Colonic (20.0%)


  • Appendiceal (18.2%)

Carcinoid tumors, irrespective of their site of origin, are associated with an increased incidence of other malignant tumors, especially those of the GI tract. Moreover, an increased incidence of breast and uterine malignancies, as well as cancer of the hematopoietic system, has been described. The reported rates of the development of a second primary malignancy with
GI carcinoid tumors is as high as 55%.206 This includes an increased risk for synchronous colorectal, small bowel, gastric and esophageal cancers, as well as metachronous lung, prostate, and urinary tract neoplasms.507 Because of the possible association with myelofibrosis, evaluation of the bowel in an individual with hematologic disease may be a useful exercise.368 An association between ulcerative colitis and rectal carcinoid tumors has also been postulated.445 The reason for the predisposition to develop other cancers may be due to the tumorigenic properties of the peptides secreted by NE cells, such as secretin, gastrin, bombesin, cholecystokinin, and vasoactive intestinal peptide.206






FIGURE 26-3. Carcinoid of the small bowel. Small bowel series. A right upper quadrant mass can be seen infiltrating the mesentery of the small bowel and proximal colon. A: Note the filling defect (arrow). B: Spot film of the same patient reveals another lesion producing a profound stricture (arrow).


Age, Gender, and Race

The condition occurs most commonly in individuals in their sixth and seventh decades.366 The mean age in Orloff’s series was 55,383 and the previously mentioned SEER study showed the mean age to be 61.4 years.351 Appendiceal tumors had been seen most frequently in women at a 2:1 ratio,426 but this has decreased to 57% in current reports. The male-to-female ratio is 0.93 for colonic carcinoids and 1.0 to 1.11 for rectal carcinoids.351 For all sites, age-adjusted incidence rates are highest in black male patients.351


Signs, Symptoms, and Diagnosis


Appendix

The presentation is usually that of an individual with right lower quadrant abdominal pain and signs and symptoms of appendicitis. The identification of the tumor, itself, usually awaits pathologic confirmation. This often is a fortuitous finding that presents somewhat of a controversy in subsequent management (see later). The prevalence of carcinoids has been estimated to be 0.32% based on a series of more than 34,000 appendectomies.355 Most are present at the tip (67%), with the body comprising 21%, and only 7% seen at the base.355


Small Bowel

Carcinoid tumors in the small bowel are frequently asymptomatic.46 In those who are symptomatic, change in bowel habits, weight loss, and abdominal pain are the most frequent complaints. Moertel and colleagues advised that the presence of an abdominal mass on the right side and a long history of weight loss and diarrhea should raise suspicion of a carcinoid in the small intestine.354 The frequency of metastases at diagnosis depends on the clinical presentation and ranges from 33% to 64%. In asymptomatic individuals, 93% who are diagnosed with small bowel carcinoids harbor metastases.354

The ileum is second only to the appendix as the site of origin of foregut carcinoid tumors.65 Quantification of 5-hydroxytryptamine and its metabolites, especially 24-hour urinary 5-HIAA, have been found to detect up to 84% of carcinoid tumors.65 Unfortunately, small bowel carcinoids commonly present late because of the nonspecific signs and symptoms that occur. This leads to failure to pursue investigative studies that could identify the lesion at an earlier stage. The single most common presenting complaint is that of small bowel obstruction, but most patients have nonspecific GI symptoms.

The most rewarding diagnostic study for the evaluation of a suspected small bowel carcinoid is enteroclysis (see Chapter 5). However, a routine small bowel series is usually sufficient (Figure 26-3). It is important to remember that small carcinoids are frequently multiple. The use of computed tomography (CT) scan to evaluate the small bowel has also been recommended (Figure 26-4), but knowledge gleaned is often ex post facto, the diagnosis of metastatic disease having already been established. Pilleul and colleagues concluded that contrast- and water-enhanced multidetector CT enteroclysis allows depiction of small bowel neoplasms with an accuracy of 84.7%.398 Magnetic resonance imaging (MRI) has also been used for the evaluation of GI carcinoid tumors. In the experience of Bader and coworkers, the primary tumor could be identified in 8 of 12 of their patients.32 The appearance is usually that of a nodular mass or bowel wall thickening with moderate enhancement on postgadolinium imaging. Liver metastases are commonly hypervascular and may be demonstrable only on immediate postgadolinium images.32


Colon

Colonic carcinoids usually grow to a large size before they become symptomatic. Even then, they are less likely to cause obstruction or rectal bleeding than adenocarcinoma of the colon. Thirty-two percent of Orloff’s patients were asymptomatic, and an additional 21% had symptoms that were the result of another condition.383 When the lesion does produce symptoms, they are indistinguishable from those caused by adenocarcinoma (e.g., bleeding, change in bowel habits, abdominal pain). Colonic carcinoids have a similar 5-year survival to that of adenocarcinoma.







FIGURE 26-4. Coronal contrast-enhanced CT scan shows large mesenteric mass encasing superior mesenteric artery and its branches. Mass was carcinoid tumor. (From Horton KM, et al. Carcinoid tumors of the small bowel: a multitechnique imaging approach. AJR Am J Roentgenol. 2004;182(3):559-567, with permission.)

Radiologic evaluation of colonic carcinoids reflects the appearance of the clinically seen lesion (Figure 26-5). For larger tumors, it is virtually impossible to distinguish the pathology from that of an adenocarcinoma. This is true even on colonoscopy or direct visualization. In the experience of Ballantyne and colleagues, 48% of the colon carcinoids were located in the cecum, 16% in the ascending colon, 6% in the transverse colon, 11% in the descending colon, and 13% in the sigmoid.38 The remainder were not assigned. As previously mentioned, patients with carcinoid tumors have an increased incidence of GI adenocarcinoma.38,47,72,407 Thorough evaluation of the entire GI tract is therefore essential.






FIGURE 26-5. Carcinoid tumor of the hepatic flexure. Spot film on barium enema reveals distension of the colon with thickened folds. This appearance is caused by an intense fibrosis and desmoplastic response produced by the carcinoid tumor.






FIGURE 26-6. Carcinoid tumor. An ulcerated nodule protruding from the rectum in a resected specimen. (Courtesy of Rudolf Garret, MD.)


Rectum

In the rectum, a carcinoid tumor usually is observed as a small, circumscribed, yellowish, submucosal nodule, 1 cm or less in diameter. It is often found incidentally, either at the time of pathologic examination of an excised rectum for another condition or in the course of clinical assessment for other complaints (Figures 26-6 and 26-7). In the Ochsner Clinic experience in New Orleans, one-half of rectal carcinoids were discovered at the time of anorectal examination of asymptomatic individuals.249 The remainder were found primarily by evaluation of patients whose symptoms were the result of other benign conditions. In a review by Mani and coworkers, the most common finding at the time of presentation was described as “nonspecific.”323 The most common complaint was that of anorectal discomfort, with rectal bleeding being the second most common. Other complaints included constipation, weight loss, change in bowel habits, rectal obstruction, “hemorrhoids,” diarrhea, and the presence
of an abdominal mass.323 Endoscopic ultrasonography has been found to be applicable for determining depth of invasion, a useful consideration if one were to consider performing a local excision.






FIGURE 26-7. Longitudinal section of the specimen shown in Figure 26-6. Note the absence of infiltration of muscularis. (Courtesy of Rudolf Garret, MD.)


Presacral Lesion

The presentation of presacral lesions is discussed later in this chapter. It is of interest to note here, however, that an unusual presentation of carcinoid has been described within the presacral space.136 In the absence of a demonstrable primary mucosal lesion, the authors concluded that the tumor arose from an enterochromaffin cell or teratoma within the presacral space or possibly a metastatic lymph node from an unknown primary.


Histopathology and DNA Ploidy

Microscopically, it is very difficult to differentiate between benign and malignant carcinoid. The usual criteria for malignancy such as mitotic activity or pyknotic nuclei are often lacking. The incidence of malignancy varies from 8% to 40%, with the evidence based on the presence of local extension or metastasis.537 The tumor is composed of uniform, small, round, or polygonal cells with prominent, round nuclei and eosinophilic cytoplasmic granules (Figures 26-8,26-9 and 26-10). Johnson and colleagues suggest that there are five generally accepted carcinoid histologic growth patterns: insular, trabecular, glandular, undifferentiated, and mixed.253 They further observed differences in median survival times in 138 patients based on these patterns and recommend the use of such stratification in future studies. Of the patients with carcinoid tumors, Bowen and coworkers reported that there was a trend to increased expression of vascular endothelial growth factor receptor (VEGFR) and insulin-like growth factor receptor (IGFR), particularly in the foregut and midgut carcinoids.64

Tsioulias and coworkers studied the nuclear DNA pattern of 22 rectal carcinoids, finding that the three with metachronous or synchronous metastatic disease had an aneuploid pattern.513 Conversely, all of the 19 tumors with no metastases exhibited a diploid pattern. The authors concluded that DNA ploidy is an important, independent prognostic indicator. Others have confirmed the association of aneuploidy with stage, size, and invasion by tumor, but in one study the data suggested that a near-hypertriploid pattern was the most precise and reliable parameter for predicting the prognosis of colorectal carcinoid tumors.87






FIGURE 26-8. Carcinoid. Uniform cells with minimal variation of cell nuclei in clusters within the lymphatic spaces. (Original magnification × 280; from Corman ML, Veidenheimer MC, Swinton NW. Diseases of the Anus, Rectum and Colon. Part I: Neoplasms. New York, NY: Medcom; 1972.)






FIGURE 26-9. Malignant carcinoid infiltrating the whole wall of the rectum and invading adipose tissue. Note the cluster of tumor cells in tissue spaces and lymphatics. (Original magnification × 80; courtesy of Rudolf Garret, MD.)


Management


Appendix

Moertel and associates recommended appendectomy alone as an adequate treatment for appendiceal carcinoids of less than 2 cm in diameter, even if lymphatic invasion is noted on subsequent histologic examination (Figures 26-11 and 26-12).353 These investigators found no recurrence in a group of more than 100 patients who had microscopic evidence of lymphatic invasion who were so treated. A later report involving 150 patients revealed no other recurrences with the same criterion.353 The authors further suggest that if the individual is elderly or at high operative risk, appendectomy alone is appropriate for even larger lesions.

A right colectomy is suggested for larger lesions in young patients and for those tumors identified to have vascular involvement or to have invasion of the mesoappendix.353 Gouzi and coworkers opined that a further indication for secondary right hemicolectomy is the presence of mucinous-producing cells.192






FIGURE 26-10. Malignant carcinoid. Uniform cells in tissue spaces, some forming abortive glandular structures. (Original magnification × 280; courtesy of Rudolf Garret, MD.)







FIGURE 26-11. Carcinoid tumor of the appendix clearly seen histologically as a submucosal nodule. (Original magnification × 80.)


Small Bowel

As suggested earlier, the major difficulty in managing patients with small bowel carcinoid is the fact that these individuals present quite late. There is a concern to which one must be sensitive, that of limiting the resection when the root of the mesentery is involved in order to minimize the risk of causing short-bowel problems. It is extremely important to examine the entire small bowel, looking for the presence of synchronous lesions (Figure 26-13). If at all possible, resection of obvious nodal involvement is encouraged, including removal of superficial hepatic metastases as well as performing a cholecystectomy. This last procedure is advised if prolonged somatostatin analogue therapy is anticipated.65


Colon

Treatment of colonic carcinoid is resection. Because these tumors are relatively slow growing, metastatic disease is not a contraindication to resection of the primary lesion. Metastases occur more frequently with carcinoids of the large bowel than with carcinoids of the small intestine. Perhaps this can be explained by the fact that carcinoid tumors may attain a considerable size in the colon before they become symptomatic.


Rectum

In the rectum, the size of the carcinoid is the distinguishing feature that determines treatment. Most tumors less than 2 cm in diameter require only local, transanal excision. In the experience of Shirouzu and associates, rectal carcinoids of less than 2 cm in diameter had neither muscle invasion nor lymph node metastases.458 Other investigators confirm the appropriateness of transanal excision for smaller lesions.249 However, those that are demonstrably invasive or are 2 cm in diameter or greater should probably be treated by a cancer type of resection.323 Laparoscopic excision of a proximal rectal carcinoid has also been described.298






FIGURE 26-12. Carcinoid tumor of the appendix. Multiple cuts through resected specimen demonstrate macroscopic confinement of the tumor to the submucosa. (Courtesy of Rudolf Garret, MD.)






FIGURE 26-13. Resected specimen of ileum showing opened bowel with incised carcinoid demonstrating yellowish hue. This was one of multiple lesions within the jejunum and ileum.


Carcinoid Syndrome

With the exception of tumors that originate outside of the intestinal tract, the carcinoid syndrome develops only in those individuals whose cancers have spread to the liver (Figure 26-14). The classic symptoms and signs are those of skin flushing, diarrhea, and a heart murmur (most commonly that of tricuspid insufficiency—Figure 26-15). The flushing may involve only the face or may involve the entire body. It may last anywhere from a few minutes to several hours. There may be excessive tearing, salivation, and facial edema, and the condition may be associated with respiratory symptoms such as wheezing. With increased involvement of the liver, the symptoms often become disabling. Pellagra is a vitamin deficiency disease most commonly caused by a chronic lack of niacin (vitamin B3) in the diet. It may also result from alterations in
protein metabolism in disorders such as carcinoid syndrome (Figure 26-16). The likelihood of developing the syndrome is dependent on the site of the cancer. Up to 60% of those with metastatic small bowel carcinoids will develop symptoms, whereas only about 1% of those with appendiceal primary disease will develop the syndrome. With the exception of the rare “case report,” virtually no one with a rectal carcinoid will ultimately develop the symptoms of carcinoid syndrome.






FIGURE 26-14. Liver showing large metastatic carcinoid tumor.






FIGURE 26-15. Heart removed at autopsy showing leaflet thickening and fibrosis, along with thickening of the chordae tendineae and papillary muscle. This resulted in massive regurgitation of the tricuspid valve.

Because of the secretion of serotonin, the diagnosis is made through its by-product, 5-HIAA, which is excreted in the urine. Some individuals with carcinoid syndrome may have normal urinary 5-HIAA levels. In such instances, the serum serotonin level must be measured in order to establish the diagnosis.

Treatment of the Carcinoid Syndrome. Treatment of symptoms of diarrhea include loperamide, diphenoxylate/atropine, cyproheptadine, and methysergide. For flushing, management includes antihistamines (e.g., diphenhydramine) and antiulcer medications such as ranitidine. Phenoxybenzamine has also been recommended for the flushing.

In addition to chemotherapy, which is often offered but usually unhelpful, a somatostatin, octreotide (Sandostatin), is advised because it inhibits the severe diarrhea and flushing episodes associated with the disease. The suggested daily program during the first 2 weeks of therapy ranges from 100 to 600 µg/day, in two to four divided, subcutaneously injected doses. Along these lines, the resected specimen should be tested for somatostatin receptors. Somatostatin analogues, such as octreotide, lanreotide, and Somatuline, have shown variable inhibition of tumor growth and therapeutic tolerance.65 Lanreotide requires injection every 10 days compared with twice daily injections of octreotide—therefore, the former may be preferred.384 An antiproliferative effect of octreotide on metastatic carcinoid, with regression of the tumors, has been reported to occasionally occur.300 The addition of interferon-α has also been successfully employed for controlling symptoms and possibly retarding tumor growth.279 Adjuvant chemotherapeutic and biomodulating therapies are under clinical investigation.65






FIGURE 26-16. Pellagra dermatitis in a patient with carcinoid syndrome.

The most efficacious program for the treatment of the carcinoid syndrome is surgically to remove (debulk) as much of the primary and secondary tumors as is possible in order to limit production of the polypeptides. Other options include hepatic artery embolization, radiation therapy, and selective hepatic artery infusion chemotherapy.

Radiotherapy and chemotherapy have not proved to be effective in the treatment of carcinoid tumors of the colon and rectum. Adequate surgical excision remains the quintessential treatment. With respect to metastatic disease to the liver, drug combinations of 5-fluorouracil and streptozotocin have achieved high, albeit brief, response rates, whereas hepatic dearterialization and embolization are also useful palliative approaches.28,505



Bowen’s Disease, Perianal Paget’s Disease, and Basal Cell Carcinoma



Cloacogenic Carcinoma and Primary Malignant Melanoma



Squamous Cell Carcinoma

Primary squamous cell carcinoma of the colon and rectum is an extremely rare tumor; approximately 75 cases have been reported.68,99,175,301,521,541 The incidence of this tumor is believed to be 1 per 3,000 malignant tumors of the bowel.99,521 These lesions tend to be distributed uniformly throughout the colon.342

Numerous theories have been postulated about the etiology and pathogenicity. These include metaplasia of glandular epithelium, embryonal rests, squamous metaplasia of existing adenoma or adenocarcinoma, damaged epithelium from toxic substances, and basal cell anaplasia.52,99,316,521 Balfour believed that this entity is either a metastatic lesion or degeneration of a poorly differentiated adenocarcinoma.36 Others suggest that this condition may represent an adenoacanthoma with primarily squamous elements (see later). Specific predisposing factors that have been associated are ulcerative colitis, radiotherapy, colonic duplication, and schistosomiasis.

Gelas and coworkers identified certain criteria that must be satisfied before one can definitively establish the diagnosis of primary squamous cell carcinoma of the rectum.175 They are as follows:



  • Metastases from another site must be excluded.


  • A squamous-lined fistula tract must not involve the affected bowel.


  • Squamous cell carcinoma of the anus with proximal extension must be excluded.

Symptoms are the same as those of adenocarcinoma, especially bleeding and change in bowel habits. Evaluation of the patient should proceed in the manner outlined in Chapters 23 and 24. Total colonoscopy is suggested because of the not uncommon association of synchronous benign and malignant tumors.

Histologic examination may demonstrate squamous metaplasia of the colonic mucosa as well as the carcinoma (Figure 26-17).

In the absence of metastases, the lesion should be treated in the same manner as that of adenocarcinoma. However, consideration should be given to implementing the neoadjuvant therapy described in Chapter 25, especially if abdominoperineal resection appears to be the surgical alternative.294 It has been described as the primary treatment for rectal
squamous cell carcinoma.413 A case report of squamous cell carcinoma of the sigmoid colon with metastatic disease to the liver has been reported that responded well to systemic chemotherapy.258






FIGURE 26-17. Squamous cell carcinoma of the cecum. Note the island of malignant squamous cells (arrows) near benign colonic glandular mucosa. (Original magnification × 50; courtesy of Rodger C. Haggitt, MD.)


Adenosquamous Carcinoma or Adenoacanthoma

Adenosquamous carcinoma of the colon is an extremely rare tumor. In 1987, Chevinsky and colleagues identified 35 cases in the literature and also noted 25 reports of squamous carcinoma primary to the colon.88 However, some authors believe that if careful review of the histologic pattern of tumors thought to be squamous carcinomas are undertaken, some of the lesions would prove to be adenosquamous cancers (adenoacanthomas), a mixture of both glandular and squamous features (Figure 26-18).92 Petrelli and colleagues retrospectively reviewed the experience at the Roswell Park Cancer Institute in Buffalo, New York, between the years 1971 and 1994.395 Seven patients were identified, representing 0.18% of the adenocarcinomas at that institution. Cagir and associates identified 145 patients with adenosquamous carcinoma of the colon, rectum, and anus in the NCI’s SEER database for the years 1973 through 1992.71 The mean age was 67 years. Twenty-eight percent of the lesions were in the right colon.






FIGURE 26-18. Adenoacanthoma of the colon. Islets of malignant squamous epithelium immediately underneath the mucosa and gland-forming tumor below that (arrows). (Original magnification × 40; courtesy of Rodger C. Haggitt, MD.)

Theoretical causes of this histologic manifestation include embryonal rests, indeterminate basal cells, squamous metaplasia, and a germ or pluripotential stem cell.88 An increased association with ulcerative colitis has been suggested.343

Adenosquamous cancers in general are very aggressive tumors and are associated with a less favorable prognosis than is adenocarcinoma.79 Because the squamous component may have a greater potential for metastasizing and can do so as an undifferentiated carcinoma, Cerezo and colleagues as well as others suggest that all such lesions be carefully evaluated by means of immunoperoxidase stains and/or electron microscopy in order to identify squamous features.79,281 This would also imply that evidence of metastatic squamous cell carcinoma does not preclude the possibility of the source being the colon. In the Roswell Park experience, all patients had stage III or IV disease upon presentation.355 Median survival was only 23 months. In three individuals, the tumor was associated with ulcerative colitis. All died of their disease.

An assessment of the Mayo Clinic experience revealed a total of 31 patients with adenosquamous cancers of the colon and rectum and 11 pure squamous cell carcinomas.168 They did not separate the two groups but reported an overall 5-year survival of 34% with a 65% survival for stage I to stage III disease. When there was nodal involvement, the survival rate was 23%, whereas without nodal involvement it was 85%. In Cagir and associates’ SEER report, the overall adjusted 5-year survival rate was 30.7%.71 The survival rate for tumors that did not demonstrate nodal involvement was comparable to that of adenocarcinoma, but more advanced lesions were associated with a poorer survival rate than adenocarcinoma stage for stage.


Stem Cell Carcinoma

Another highly aggressive tumor of the colon and rectum may be a variant of adenoacanthoma, the so-called stem cell carcinoma. In theory, there may be a pluripotential stem cell in the mucosa of the GI tract capable of differentiation in several directions.386 Only a few cases have been reported. Palvio and colleagues reviewed tumors with adenosquamous and carcinoid elements in one patient and exocrine, NE, and squamous differentiation in another.386


▶ TUMORS OF LYMPHOID ORIGIN


Lymphoid Hyperplasia, Benign Lymphoma, and Lymphoid Polyp

Lymphoid hyperplasia is a benign, focal, or diffuse condition that occurs typically where clusters of lymphoid follicles are present (terminal ileum, rectum).106,107,133,219 Although the etiology is unknown, the possibility of an inflammatory reaction as well as a hereditary predisposition has been suggested. In children, an infectious process is thought to precipitate the acute form of the disease.256

One of the earliest reports of benign lymphoid hyperplasia was by Cohnheim who, in 1865, introduced the term gastrointestinal pseudoleukemia.96 He described a hyperplasia of the lymphoid follicles of the GI tract with polyp formation but without the blood picture of lymphatic leukemia. In 1940, Ewing stated that “the gastrointestinal tract is the seat of a remarkable form of primary lymphoid hyperplasia which lacks the destructive character of lymphosarcoma and fails to give lymphocytosis in the blood.”147 He pointed out
that lesions of the GI tract may be limited or diffuse and sometimes are associated with widespread lymphoid hyperplasia but never with leukemia. Symmers confirmed these findings in 1948.495 Since that time, isolated cases have been reported sporadically, all of which confirm the benign nature of the disease.70,98,108,242,256

In 1961, Cornes and colleagues reviewed 100 such patients.107 The tumors were described as usually single and most frequently found in the lower one-third of the rectum. They may be seen in an individual at any age, but in adults they are most commonly noted during the third and fourth decades.70,107,405 In children, the peak incidence is between 1 and 3 years and is twice as common in boys as in girls.12,256

Gruenwald suggested that the lesions are congenital malformations or hamartomas, a hypothesis that is supported by their occasional familial occurrence.202 Granet reported solitary benign lymphomas in identical twins.193 Beatty and Keeling noted the lesions in three siblings, ages 6, 7, and 9 years.48 Others have observed an association with familial polyposis.199,520

Lymphoid hyperplasia is characterized radiographically by small, uniform, localized, or generalized polypoid lesions (Figure 26-19). A fleck of barium may be seen in the center of the polyp on contrast study, representing umbilication at the apex of the lymphoid nodule. A central dimple in the nodule is considered good evidence for making the diagnosis.254 Endoscopic examination with biopsy confirms the nature of the lesion. The nodules are usually small, firm, and sessile but occasionally may be large and can become pedunculated (Figure 26-20). When removed and sectioned, the tumors are found to be composed of well-differentiated lymphoid tissue, with follicles separated by white fibrous bands and covered by a rather thin mucous membrane. The macroscopic and microscopic appearance may resemble malignant lymphoma or Hodgkin’s disease. In fact, the condition has been regarded by some as a form of malignant lymphoma and has even been designated as pseudolymphoma.495 However, the lesion lacks the infiltrating and destructive characteristics of malignant lymphoma and does not become disseminated. In the benign lymphoid polyp, a follicular pattern with a clearly defined germinal center is seen (Figure 26-21), whereas malignant lymphoma shows a poorly defined and irregular pattern with no germinal centers.405 The condition also can resemble leukemic infiltration of the bowel, but in leukemia the lesion tends to have a segmental distribution (Figure 26-22). In addition, evidence of the disease is usually apparent in the peripheral blood smear.






FIGURE 26-19. Lymphoid hyperplasia. Numerous small filling defects are evident in the rectum on this air-contrast barium enema study.







FIGURE 26-20. Colonoscopy reveals numerous confluent, sessile, mucosal nodules. Biopsy was consistent with nodular lymphoid hyperplasia.




Malignant Lymphoma

Malignant lymphoma, as a primary lesion or as part of a generalized malignant process, may involve the GI tract. This is the most common site for extranodal non-Hodgkin’s lymphomas.437 As a primary tumor lymphoma comprises between 1% and 4% of all GI malignancies, but only 0.5% of colonic and 0.1% of rectal cancers.335,454 Gastric involvement is more common than that of small or large intestinal lymphoma and carries a better prognosis.102 Colonic lymphoma preferentially involves the cecum and the rectum with 60% to 74% of colorectal lymphomas occurring in the cecum.548 However, concurrent tumors elsewhere in the large bowel, the small bowel, and the stomach have been reported.

Malignant lymphoma of the colon has been reported in association with a variety of other entities, especially those of altered immune status (e.g., AIDS; see Chapter 10).8,125,148,240,262,271,299,302,369,379,393,490,526 A high-grade B-cell lymphoma in an individual infected with HIV is considered an AIDS-defining condition.434 Most intestinal lymphomas in the AIDS population are of the non-Hodgkin’s type. GI non-Hodgkin’s lymphoma represents 17% of those with extranodal involvement.434

Waldenström pointed out considerable overlap among macroglobulinemia, lymphoma, and lymphocytic leukemia.526 This was exemplified by a case reported by Levy and coworkers in which cecal lymphoma developed in an 81-year-old individual while the patient was receiving immunosuppressive therapy for macroglobulinemia.302 Associations with chronic ulcerative colitis, Crohn’s disease, and celiac disease have also been observed.304 With the concern for possible
concomitant leukemia, total and differential white blood cell counts are mandated as part of an evaluation.544

In most series, the incidence is greater in men than in women by a ratio of almost two to one.550 Most patients are older than 50 years of age at diagnosis, but the condition can occur at any age.


Signs and Symptoms

Many individuals complain of abdominal pain that is usually cramping and localized to the area of the tumor. Other prominent symptoms include weight loss, change in bowel habits, diarrhea, weakness, nausea, vomiting, anorexia, bleeding, and fever. Discrete intra-abdominal masses are generally not appreciated until late in the course of the disease. The breakdown of signs and symptoms according to Fan and coworkers (37 patients) is as follows149:



  • Abdominal pain (65%)


  • Abdominal mass (54%)


  • Weight loss (43%)

The symptoms produced by rectal involvement are variable and largely depend on whether the growth has become ulcerated. In early stages, with an intact mucosa, symptoms consist of a bearing-down sensation or a feeling of fullness in the rectum, with some rectal irritability and low backache. When ulceration of the overlying mucosa has developed, bleeding and mucous discharge may be noticed. Later, pain and soreness are described if the growth begins to encroach on the anal canal. A high index of suspicion must be maintained in homosexual patients, and obviously if AIDS is known or suspected. Obstructive symptoms are unlikely to occur because the primary growth often remains fairly localized to one quadrant and does not usually extend in an annular fashion as seen with carcinoma.


Pathogenesis

It is thought that malignant lymphoma starts in the submucosal lymphoid tissue, which in places extends into the mucosa. It is not known whether it begins multicentrically or arises from a single area and later spreads by direct extension or through lymphatic channels. At presentation, a large segment of colon may be involved in a uniform and continuous fashion. Submucosal infiltration often extends beyond the area of obvious involvement, and additional lesions may be found apart from that region. Marked involvement is most common in the ileocecal or the rectosigmoid area, where tumors sometimes become confluent and form a large conglomerate mass. This may cause intussusception and intestinal obstruction. In the ileocecal region, the process usually extends into the appendix and into the ileum for a variable distance. When the rectum is the site of the tumor, inguinal nodes may be enlarged and palpable. Extensive serosal or retroperitoneal involvement is not characteristic of diffuse lymphoma.


Endoscopy and Radiology

Clinical and radiographic diagnosis of colonic and rectal lymphoma may be obscured by the variety of appearances it may assume. Usher reported 10 patients with rectal lymphoma from the Mayo Clinic and observed that in all cases the lesion was visualized on proctoscopic examination.517 In no instance could a definite diagnosis of lymphoma be made by the appearance of the lesion. Usually, it was described as a polypoid tumor, diffuse proctitis, a submucosal nodule, or carcinoma (Figure 26-23). The endoscopic appearance may resemble that of Crohn’s disease, such as has been described for the extremely rarely reported cases of granulocytic sarcoma and malignant histiocytosis.77,436

From the radiologic point of view, diffuse lymphoma of the colon must be differentiated from familial polyposis, ulcerative colitis with pseudopolyposis, granulomatous colitis, nodular lymphoid hyperplasia, and schistosomiasis. Although radiologic differentiation from carcinoma may be impossible, Halls pointed out that certain presentations strongly suggest lymphoma: presence of a bulky extracolonic component, concentric dilatation of the lumen, and a polypoid filling defect of the terminal ileum and ileocecal valve (Figures 26-24 and 26-25).209






FIGURE 26-23. Lymphomatous infiltration of the rectum treated by abdominoperineal resection. Multiple lesions (arrows) are noted. (Courtesy of Rudolf Garret, MD.)







FIGURE 26-24. Malignant lymphoma. Postevacuation barium enema demonstrates multiple polypoid filling defects of varying size with areas of ulceration.


Pathology

Macroscopic examination of the tumor reveals a polypoid or ulcerated mass resembling carcinoma or a diffuse process extending over a large segment of colon, sometimes with numerous polypoid intraluminal excrescences. The bowel wall is thickened and rubbery in consistency, and its cut surface demonstrates a greatly thickened mucosa, often with prominent convoluted folds resembling the surface of brain and reaching a thickness of 1 or 2 cm (Figure 26-26). The submucosa is markedly thickened as a result of infiltration by closely packed tumor cells. In contrast to disease in the small bowel, deep ulceration and perforation are uncommon. However, superficial ulceration and necrosis may be seen.

The presence of a nonulcerated, submucous tumor in the rectal wall requires differentiation from benign lesions, such as lipoma, myoma, and nodular lymphoid hyperplasia, and also from an inflammatory condition, such as an intramuscular abscess. Thus, biopsy and histologic examination are crucial to the evaluation of such lesions (Figures 26-27 and 26-28). Microscopic examination usually readily distinguishes lymphoma from other malignancies.519 However, a nonspecific lymphoid infiltrate in the mucosa and submucosa may present a problem with differential diagnosis. Under these circumstances, some investigators have recommended immunocytochemical studies as well as gene rearrangement analysis with DNA probes to elucidate the precise nature of the process.378

Regional lymph nodes are involved in approximately onehalf of the patients at the time of laparotomy. The presence of enlarged nodes may, however, represent reactive lymphoid hyperplasia and must be carefully examined histologically to document the presence of tumor. Because involvement beyond a single segment of bowel and its regional nodes excludes the diagnosis of primary lymphoma, a careful search for additional diseased nodes is necessary.






FIGURE 26-25. Malignant lymphoma of the cecum. Note the large, lobulated mass.


Classification

Malignant lymphoma is classified based on its cellular morphology and immunologic surface markers. Included are
the following histologic types: lymphocytic lymphoma, lymphosarcoma, reticulum cell sarcoma, giant follicular lymphoma, and Hodgkin’s disease. Hodgkin’s disease of the colon or rectum is the rarest.






FIGURE 26-26. Resected specimen showing lymphoma of the cecum. Note the convoluted folds.






FIGURE 26-27. Lymphoma of the sigmoid colon. Note the heavy infiltrate of lymphocytic tumor cells involving the mucosa and submucosa. (Original magnification × 80; courtesy of Rudolf Garret, MD.)

Tumors are also classified based on the extent of involvement:

Class I: confined to bowel wall

Class II: regional node involvement within the drainage area of the bowel primary tumor

Class III: para-aortic node involvement; direct extension to adjacent viscera

As pointed out by Wychulis and associates and by others, the prognosis of primary extranodal lymphoma in the colon or rectum is not clearly related to cell type but is affected by stage.149,304,438,550




Extramedullary Plasmacytoma

Primary plasmacytoma is a localized plasma cell tumor that is most commonly found in the nasopharynx, although it has been described in many other parts of the body. Plasma cell neoplasms are classified in five categories: multiple myeloma, solitary myeloma, extramedullary plasmacytoma (with multiple myeloma), plasma cell leukemia, and primary plasmacytoma.460

The condition involves the colon extremely rarely with fewer than 10 cases having been reported as a primary disease. Some have involved the bowel secondarily. Primary tumors elsewhere in the GI tract have also been noted.189,212,218 Disseminated multiple myeloma is often diagnosed in patients who have a localized plasmacytoma if these patients are followed for a sufficiently long period. Therefore, a bone marrow examination should be performed at some point once an extramedullary plasmacytoma has been diagnosed. Primary and secondary colorectal plasmacytoma is more common in men than in women by a ratio of 3:2.

Presenting symptoms include abdominal pain, bleeding, anorexia, nausea, vomiting, and weight loss. The tumor can be single or multiple and may consist of diffuse cellular infiltrates or of polypoid or nodular protrusions. Microscopic examination demonstrates the characteristic population of plasma cells (Figure 26-29). Identification by means of immunoperoxidase staining has also been advised.183

Treatment ideally consists of total excision when possible. If, for example, a GI lesion has been excised for purposes of diagnosis and the entire tumor was removed, no additional treatment would in all probability be indicated. Of the cases reviewed by Sidani and associates, none metastasized to any organ other than lymph nodes.460 Plasmacytomas that are not readily resectable may be responsive to radiotherapy. The use of chemotherapy is restricted to disseminated disease.







FIGURE 26-29. Extramedullary plasmacytoma. A: Colonic gland surrounded by atypical, infiltrative plasma cells. (Original magnification × 100.) B: Many plasma cells, some of which demonstrate hyperchromatic and eccentric nuclei. Note the apophyllic cytoplasm, a characteristic feature of plasma cells. There are also binucleate forms with discernible nucleoli. (Original magnification × 400.)


▶ MESENCHYMAL TUMORS


Fibrous Tissue Origin


Fibroma

Fibroma of the colon is a very rare tumor that belongs to the uncommon spindle cell group of benign tumors that also includes leiomyomas.479 Its incidence is only one-tenth that of leiomyoma, however.66

Although many authors use the terms fibroma, leiomyoma, and fibromyoma interchangeably, Rose emphasized that differential histologic tissue staining techniques distinguish the true fibroma from other spindle cell tumors.424 According to Aird, the tumor may originate in any layer of the bowel wall but arises most frequently in the submucosa.6 Fibromas have been reported in the appendicular stump and near the mesentery.154,511 Reports of fibroma of the colon are few.23,150,381,424 Abdominal pain and distension may be noted, and resection is the treatment of choice.

Fibroma of the anorectal region is very rare. It may arise from a hypertrophied papilla or by fibrous infiltration of a large prolapsing internal hemorrhoid, generally as a result of repeated attacks of thrombosis and strangulation without sloughing. It is encapsulated, firm, slightly movable, ovoid, of small to moderate size, and has little tendency to ulcerate. It is usually situated in the wall. In time, the covering of columnar epithelium becomes converted into squamous epithelium. A smooth, pale fibrous polyp results. The tumor may remain in the wall of the rectum or become polypoid and extend into the lumen. In general, it is single and of slow growth. However, fibrous polyps may be multiple, so a careful proctoscopy is essential.

Symptoms include tenesmus and a sense of heaviness in the rectum. If ulceration has occurred (an exception), bleeding may be noted. The diagnosis is seldom made without microscopic examination. Transanal excision is the appropriate treatment.


Inflammatory Fibroid Polyp or Eosinophilic Granuloma

Inflammatory fibroid polyp is a rare, focal lesion occurring in the submucosa of the GI tract, least commonly in the colon.255,305,400 Only a few cases have been reported.334,338,387,523 Another term for the condition is eosinophilic granuloma. Although the etiology is uncertain, the observation of the proliferation of submucosal mesenchymal fibrous tissue as well as variable eosinophilic infiltration suggests the effect of an inflammatory stimulus (Figure 26-30).305

Rectal bleeding, tenesmus, change in bowel habits, and diarrhea are the most common symptoms. Obstruction resulting from intussusception has also been reported.305 Radiographically, the impression may be that of a carcinoma.338 Because malignant degeneration has not been noted, however, endoscopic removal is suggested. A concern is that lesions may be sessile and submucosal and have a tendency to bleed readily. If colonoscopic resection is unsuccessful or inadvisable, colectomy or colotomy and polypectomy should be performed.


Fibrosarcoma

Of the sarcomas involving the GI tract, fibrosarcoma is one of the rarest. Stoller and Weinstein reported 21 cases of fibrosarcoma of the rectum in the literature from 1927 until 1954 and added 2 cases of their own.483 The mean age of the patients in this series was 51 years. All tumors were situated in the rectum within 10 cm of the dentate line. Only 2 cases of fibrosarcoma of the colon have been reported.45,228 Espinosa and Quan identified the only case of anal fibrosarcoma.145 The lesion apparently arose at the site of a previous fistulectomy incision.

The most common presenting symptom of fibrosarcoma of the rectum is difficulty with defecation. Pain is the second most common symptom, and bleeding, third.483 Proctosigmoidoscopic examination may reveal the tumor to be consistent with an adenocarcinoma, and only histologic determination can establish the definitive diagnosis.

Microscopically, the tumor is characterized by strands of fibrous tissue that infiltrate the adjacent structures of the bowel wall but tend to spare the mucosa until late in the disease (Figures 26-31).483 The presence of mitoses is helpful in confirming the malignant nature of the lesion.

Treatment is essentially the same as that for adenocarcinoma: radical resection of the involved bowel with or without a sphincter-saving approach. Neither radiotherapy nor chemotherapy has been helpful in the management of this rare condition.







FIGURE 26-30. Inflammatory fibroid polyp. The bowel wall is infiltrated by many eosinophils. Note some fibroblasts and small blood vessels lined by prominent endothelial cells. (Original magnification × 280; courtesy of Rudolf Garret, MD.)


Malignant Fibrous Histiocytoma

Malignant fibrous histiocytoma is an extremely rare fibrosarcoma variant in which histiocyte-like cells are present.39,452,530 The term was originally proposed by O’Brien and Stout to describe tumors composed of both fibroblasts and histiocytes (Figure 26-32).376 The lesion is usually found in the lower extremity.

It is difficult to present a meaningful evaluation of the signs, symptoms, diagnosis, therapy, and prognosis with such an uncommon condition. Tumors tend to be large, present with obstructive symptoms, and are thought clinically to be adenocarcinomas. Treatment is radical resection, but prognosis is presumably poor. A partial response has been reported with chemotherapy.210


Stromal Origin


Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are sarcomas arising from mesenchymal tissue. They are believed to represent the most common nonepithelial sarcoma of the GI tract, comprising approximately 0.1% to 3% of all GI cancers and approximately 5% of soft tissue sarcomas. GISTs can occur anywhere in the GI tract but most commonly arise in the stomach (65%) or small intestine (25%); about 5% to 10% of GISTs are located in the colon and rectum.185 GISTs are related to the musclelike nerve cells, the interstitial cells of Cajal, which coordinate the autonomic movements of the GI tract. Although the exact incidence is still somewhat unclear, it is now estimated that between 5,000 and 10,000 people each year develop GISTs. GISTs have a slight male predominance with the median age of diagnosis approximately 60 years.185 There appears to be an association with neurofibromatosis, and there have also been reports of germ line mutations in the KIT proto-oncogene.



Diagnosis and Tumor Behavior

The diagnosis of GIST is usually made on biopsy or, more commonly, at the time of exploratory laparotomy that was performed for an unknown mass. However, the diagnosis of GIST may be suggested by preoperative CT through the presence of a large mass without adenopathy.101 An incidental extrarectal mass may be felt or seen at the time of routine digital examination, proctoscopy, or colonoscopy (Figure 26-33).

In GIST, a specific DNA mutation causes the tyrosine kinase enzyme, known as KIT proto-oncogene, to be switched “on” all the time. KIT encodes for a transmembrane receptor tyrosine kinase signaling molecule, which is responsible for sending growth and survival signals inside the cell. If it is “on,” the cell stays alive and grows or proliferates. The overactive mutant KIT enzyme triggers the uncontrolled growth of GIST tumor cells. KIT can be identified by looking for a portion of the enzyme, the CD117 antigen. The presence of CD117 is, in fact, a defining feature of GIST and is widely used to confirm the diagnosis. GIST tumors have also been found to contain a
mutation in platelet-derived growth factor receptor alpha (PDGFRA).186






FIGURE 26-33. Malignant gastrointestinal stromal tumor (GIST). A: Extrarectal mass seen on retroflexion of colonoscope demonstrating mucosal preservation. B: Endorectal ultrasound shows a posterior mass of mixed echogenicity that upon excision proved to be a GIST.


Distinguishing benign from malignant tumors may be quite difficult. It is important to recognize that the current concept is that all GISTs are at risk for malignancy (Figure 26-34). The location of the tumor seems to affect behavior, but the most important prognostic factors for malignant risk are tumor size at diagnosis and mitotic count.346 Still, a small GIST in the small intestine may grow more quickly and be more likely to spread than a large gastric tumor. When a GIST metastasizes, it usually spreads to the liver or peritoneal cavity but rarely spreads to the lymph nodes.




Smooth Muscle Origin


Colonic Leiomyoma

Smooth muscle tumors of the alimentary tract are rare, and benign smooth muscle tumors of the colon are exceedingly uncommon. Stout conducted a 50-year study in which he found 30 leiomyomas in 200 benign neoplasms.484 In a 15-year study, Ferguson and Houston reported 2 leiomyomas from a total of 67 benign tumors.152 Skardalakis and Gray reviewed 59 cases of leiomyomas, and MacKenzie and coworkers collected reports of 19 cases from the literature and added 8 of their own.318,464

Smooth muscle tumors are found in patients of all ages, with a gradual increase in frequency and malignant degeneration up to the sixth decade.270 The tumor is classified according to its appearance and direction of growth. The intracolonic type may be pedunculated or sessile. The extracolonic type grows away from the lumen of the bowel and lies in the abdominal cavity attached to the wall. The dumbbell type grows into the lumen and into the abdominal cavity simultaneously. This type of tumor accounts for 4% of all smooth muscle tumors of the GI tract. These usually reach a much larger size than those with unilateral spread. The constrictive type encircles a variable length of bowel. Lookanoff and Tsapralis observed that the sigmoid and transverse colon seemed to be the most common sites and that very few leiomyomas were found in the cecum.309

The tumor may be an incidental finding in an asymptomatic individual, or the patient may present with pain or a lump. Perforation, intestinal obstruction (secondary to the tumor itself or to intussusception), and hemorrhage have been reported.85,362

Macroscopically, the tumor appears well encapsulated. On cross section, leiomyomas have a fleshy appearance;
because the tumor is under pressure, it tends to protrude (Figures 26-35,26-36,26-37 and 26-38).






FIG. 26-34 A: Small-bowel gastrointestinal stromal tumor with a diffusely thickened bowel wall. B: Gastrointestinal stromal tumor. Image obtained in the same patient as in the previous image. A more caudal portion of the tumor has areas of necrosis (arrows), with air present within the necrotic cavity that communicates with the lumen of the small bowel. C: Spindle cell GIST shows uniform cigar-shape cells with elongated nuclei (H-E stain X40). D: Formalin-fixed, paraffin-embedded human gastrointestinal stromal tumor stained with peroxidase-conjugate and DAB chromogen. Note cytoplasmic/membranous staining.

Histologically, a typical spindle cell neoplasm can be observed (Figure 26-39). Most investigators believe that the mitotic rate is the single most important criterion for diagnosis of malignancy.53,63,146,485 Other indicators are a variation in nuclear size and shape, hyperchromasia, frequent bizarre cells, and difficulty in identification of longitudinal myofibrils.53,63,146 If the mitotic rate is high, if the growth is rapid, if an ulcer is present, or if the lesion is greater than 2.5 cm in diameter, malignant degeneration should be suspected. Smooth muscle tumors are usually locally invasive, but metastasis from a primary tumor in the GI tract has been described.63

Radiologic features vary depending on whether the tumor is intramural, submucosal, subserosal, or dumbbell shaped.35



Rectal Leiomyoma

Only a few cases of rectal leiomyomas have been reported.16,372,442,451 Vorobyov and colleagues reported their
experience at the Research Institute of Proctology in Moscow.525 Thirty-six patients with benign leiomyoma of the rectum underwent surgery between the years 1972 and 1990. Approximately one-third were male. In this experience, the tumors often tended to arise from the internal anal sphincter. Some investigators have found that endorectal ultrasound is helpful in determining the limits of the lesion.451 A homogeneous hypoechoic tumor without invasion of the perirectal tissue may be noted.236






FIGURE 26-35. Pedunculated leiomyoma.

Smaller myomas usually cause no symptoms, can be found on routine rectal examination, and are usually removed with a diathermy snare or by transanal excision. Large lesions may cause interference with defecation, a sense of fullness in the rectum, and a frequent desire to defecate. Because of these distressing symptoms and the possibility of obstruction and malignant degeneration, removal of the growth is indicated.

When the tumor is essentially extrarectal, it is best to excise it by means of an extrarectal approach rather than transanally. Even large tumors may be treated by local excision, but if clinical suspicion of malignancy exists, such as ulceration, hemorrhage, or extrarectal fixation, radical surgical treatment by excision of the rectum is indicated. Biopsies may be difficult to interpret in such cases. In the experience of the group from the Research Institute of Proctology, one-third of their patients (n = 12) harbored lesions less than 1 cm in diameter, and these were all removed by means of transanal excision.525 An additional 10 patients with tumors from 2.5 to 5 cm also were treated by this approach. Six other individuals underwent excision by means of a perirectal operation, whereas abdominoperineal resection or abdominoanal operations were performed in those with tumors measuring from 8 to 20 cm. Recurrence was found in 9 patients, all of whom had local procedures. In 7, malignant transformation was the reason.






FIGURE 26-36. Leiomyoma. A well-encapsulated mass in the bowel wall. (Courtesy of Rudolf Garret, MD.)






FIGURE 26-37. A leiomyoma resected from the hepatic flexure reveals a fleshy tumor on cross section. (From Corman ML, Veidenheimer MC, Swinton NW. Diseases of the Anus, Rectum and Colon. Part I: Neoplasms. New York, NY: Medcom; 1972.)


Leiomyosarcoma


Colon

Leiomyosarcoma of the large bowel is a very rare lesion. The total number of published cases is probably fewer than 150, although many would today probably be classified as GIST
tumors (see earlier discussion).21,30,35,73,90,119,234,412,449,480 No age predilection for this disease is apparent. It affects the genders equally and is more than twice as common in the rectum as it is in the rest of the colon.






FIGURE 26-38. Sigmoid colectomy reveals characteristic leiomyoma in the bowel wall.






FIGURE 26-39. Leiomyoma of the colon. Spindle cell neoplasm filling the submucosa with thinning of the overlying mucosa. Nuclei are blunted at ends with surrounding vacuoles. There is no evidence of mitoses or pleomorphism. (Original magnification × 100.)

Leiomyosarcoma arises from the smooth muscle of the bowel wall (Figure 26-40). A very insidious disease, it can remain asymptomatic for a long period. Weight loss is almost never recorded, but pain is a common symptom. Tarry stools and the sequelae of anemia are the most frequent presentations (Figure 26-41). A palpable tumor is almost always present when the lesion occurs in the rectum, and in some instances, obstruction is also seen.

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Jul 17, 2016 | Posted by in GASTROENTEROLOGY | Comments Off on Less Common Tumors and Tumorlike Lesions of the Colon, Rectum, and Anus
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