• are you a producer of the cancer-associated adenomatous polyps? If so, you need periodic careful follow up...possibly surgery.
• do you already have a cancer?
• hereditary nonpolyposis colorectal cancer (HNPCC) usually occurs in people younger than age 45.

Benign Lesions:

• non-tumorous, non-"growth" polyps:
  • bowel-prep-induced pseudopolyp: [temporary mucosal edema][LMC-02-4467A]
  • "simple polypoid tag": (polypoid exaggerated mucosa; mucosal "tag")[S-01-5948]; sometimes simple elongation of crypts with increased mucous-cell component but not in a case of IBD [S-01-6857; S-01-7899]; a 2 cm. polypoid malformation [S-02-4311] mucosal malformation "tag"...simple polyp [S-01-7366; LMC-02-4467B]
  • SRUS (solitary rectal ulcer syndrome) polyp: traction tag heading toward forming a "solitary ulcer"
  • lymphoid polyp: enlarged, normally-located mucosal lymphoid nodule.
  • everted colonic diverticulum (it "reverts" upon gentle endoscopic pressure ).
  • pneumatosis cystoides intestinalis
  • inverted hamartomatous polyp (localized colitis cystica profunda...looks like a submucosal mucocoel) [LMC-01-3740]
• tumors or growths, benign: Cardinal Rule: you must have/get an idea of lesion size and location when interpreting slides of colonic growths! The few small colonoscopic biopsies taken may not reflect the true lesion (especially those epithelial lesions with potentially mixed components)...we have seen many instances of polyp biopsies failing to show the adenomatous area or the malignant area.
  • juvenile polyp: marked expansion of lamina propria elements.
  • elastofibromatous polyp: polyp due to lamina propria accumulation of elastotic fibers remindful of actinic elastosis. [S-04-12744].
  • inflammatory polyp (or pseudopolyp): usually, but not necessarily, associated with IBD & with IBD can be extensive & even as filiform polyposis.[S-01-7388].
  • soft tissue polyps: lipoma ([LMC-03-5210]); ganglioneuroma [S-02-4741; S-02-12558; S-03-13548; LMC-04-4740; S-04-9790]; angiomyolipoma [LMC-03-7817]; leiomyoma [S-04-290].
  • xanthelasma of mucosa: lamina propria (usually) accumulation of foamy macrophages (usually a yellow lesion).
  • Peutz-Jeghers syndrome hamartomatous polyp: villous architecture & non-layered lining cells...at 1st glance they look adenomatous but are not dysplastic.
  • serrated polyps:
    • hyperplastic polyp, classical (HPP): pure; serrated only in upper 50% of crypts & simple crypt outlines, otherwise & almost always no larger than 1.0 cm.; rounded/exophytic; hyperplastic epithelial tufting & Ki67 shows that proliferative nuclei are in deep half-to-66% of crypts; & crypt bases are not (1) dilated or (2) horizontally outpouched. No adenomatous (dysplastic) component. 3 types¹⁰: goblet cell rich, microvesicular, & mucin poor.
    • hyperplastic with adenomatous (MHAPs): mixed; differs from (TSA), below, because any adenomatous foci are "traditional" (straight/tubular & sharply demarcated) & negative for "serratedness" in adenomatous component. HPP in transition to AP? Had growth continued, the adenomatous component is presumed to subsequently overwhelm the HPP.
    • traditional serrated adenoma (TSA):1990 report¹¹; looks pretty uniform¹⁰; serrated/sawtoothed lumenal surface contour & sawtoothed infolding & undulation of crypt epithelium; major population is eosinophilic columnar cell with centrally placed elongated nucleus & may be mildly stratified (but not to degree of TA or VTA) but Ki67 very low in this component...some cytologic dysplasia always present¹⁰; can be sessile or pedunculated¹⁴ & suspect it when you have a pedunculated polyp that does not readily appear to be adenomatous...especially if [warning] greater than 1.0 cm. (may have such a small adenomatous component that it takes Ki67 to recognize it¹²). Can have TSA & HPP butted together (below) & initially remindful of MHAP, above¹⁴. Probably no more cancer associated risk than HPP¹⁰. [LMC-01-8025; S-02-11695; /c cancer LMC-05-7076; /c cancer LMC-05-6990; /c branching S-05-10804]
    • sessile serrated polyp (SSP/SSA): classically pure & not mixed; 1996⁵ report¹³; tends (but not always) sessile and is the lesion in the old-terminology condition, "hyperplastic polyposis¹⁰ [L-05-7966?]" which had an increased cancer risk. Suspect in small biopsies of larger lesion [warning] when see HPP-like biopsy with too much pseudostratification or with eosinophilic cells pseudostratified & cytology like TSA¹⁰. SSA begins as a non-adenomatous, non-cytologically dysplastic (but may have "bottom up" nuclear atypia to mid/upper crypts, with rounded nuclei & nucleoli) proliferation BUT with architectural dysplasia with deep-crypt dilation, branching⁴, even horizontal/lateral outpouching or branching near muscularis¹⁰. May have a mitosis in upper third of crypt. Abnormal deep areas lined by excess cells of goblet or gastric-foveolar cell morphotypes/phenotypes¹⁰..."hypermucinous" change; when adds focal adenomatous component, is on the precancerous transition track¹⁰. Tends to be large, sessile, and right-sided⁵ [S-05-10858]. Thought of as slowly cancer risk associated, especially when a polyposis case¹⁰...and leads through adenomatous stage and progenitor of the "serrated adenocarcinoma". We see many instances throughout the colon of adenomatous polyps which have residual "hypermucinous change (in such cases, one might suggest that the polyp may have arisen by the "serrated pathway".
  • adenomatous polyp (traditional) (AP): DIAGNOSIS: (these polyps have "dysplasia": (1) histo-architectural: altered cell concentration & normal zonality as pseudostratification includes the crypt out to the colonic lumenal surface & polarity becomes lost; (2) cytologic dysplasia (mild & moderate = low grade; severe = high grade¹⁵): loss of columnar-cell simplicity with nuclear changes (enlargement, hyperchromia, & increased N/C ratio & decreased cytoplasmic mucous); (3) IHC-marker [Ki-67] demonstrated loss of proliferative confinement to the deep 50% of cypts [S-06-8606]). SPORADIC vs. GENETIC ...hereditary polyp associated syndromes: Lynch I & II; Muir's or Torre's; Down family syndrome; Bloom's; dyskeratosis congenita, etc.) [warning].
    • flat/sessile adenoma: can be villous, tubular, or villotubular.
    • villous adenomatous polyp (VA) (30% of those larger than 5CM contain a cancer⁶[warning]):
      • with usual adenomatous features: variable dysplasia
      • with excessive mucous cells (hypersecretory adenoma): usually low grade dysplasia, rectal location, and can be highly potassium losing lesion leading to electrolyte problems⁶. [LMC-05-6642]
    • tubular adenomatous polyp (TA):
    • tubulovillous adenomatous polyp (TVA):
    • mixed adenomatous and hyperplastic⁶: a hyperplastic polyp with discrete adenomatous areas & the adenomatous component does not have serrated lumenal surfaces (the tubules are straight/tubular); see serrated category, above.
    • entrapment: polyp with entrapped adenomatous component vs. cancer (DDX) [S-04-1740]
    • DALM ?: adenomatous polyps in a case of IBD vs. DALM (dysplasia associated lesion or mass; that is, is the lesion in the IBD case a relatively harmless sporadic adenoma or the relatively dangerous...DALM...harbinger of cancer in IBD?). (p352 discussion¹⁴ ).
    • familial polyposis information ( some known hereditary polyposis syndromes, include):
      • Familial adenomatous polyposis [FAP]
      • Attenuated adenomatous polyposis coli [AAPC]
      • Juvenile polyposis, hyperplastic polyposis
      • Hereditary mixed polyposis syndrome
      • some registries are members of the international Leeds-Castle Polyposis Group and the Collaborative Group of the Americas on Inherited Colorectal Cancer.
  • carcinoid (vast majority in the appendix): when found in rectum, if 1.0cm or less, biopsy and destroy
    • adenocarcinoid: worse behavior than classical carcinoid but not as bad as adenocarcinoma [another in 2004; LMC-05-4696].
    • general info here [L07-522].
      
  • tumors or growths, malignant:
    • carcinoma:
      • adenocarcinoma (very common):
        • intra-epithelial adenocarcinoma: this is CIS and has a convincing degree of epithelial polarity alteration and no evidence of intramucosal invasion; some¹⁵ view this as just an adenoma because there is no risk of metastasis.
        • intramucosal adenocarcinoma: ca. invades the lamina propria...which has no lymphatics...& does not breach the muscularis mucosae into the submucosa & is biologically identical to CIS...no mets even if grade III & some¹⁵ view it as an adenoma.
        • intrapolypoid ca. vs. pseudoinvasion; in endoscopically removed malignant polyps, pathologists should note: (1) measured proximity of the cancer to the endoscopic resection margin, (2) the tumor grade (degree of differentiation), (3) and whether or not any angiolymphatic invasion is seen¹⁵.
        • lymph node dissection:
          • NODEs: since node "positivity" adds adjuvant chemotherapy, then failure to find all nodes potentially denies life-saving therapy [our outstanding performance] if a positive node was missed. How much advantage will adjuvant (a "pre-emptive strike" against possible cells still in your body) chemotherapy give...Adjuvant!online...free registration and online use.
          • PTDs: very important to distinguish PTDs (pericolonic tumor deposits...especially if grossly palpable) from positive nodes (Cancer, 88:2228-2238, 2000 & ref.¹⁴), the latter either having residual lymph node component &/or a circumscribed (ovoid or round) cross-sectional profile¹⁴, lack of lymphoid foci & circumscription being diagnostic of a PDT (but a PDT can have some lymphoid foci as host reaction [L08-8186]). Some suggest thatpresence of PTDs is so detrimental as to represent pM positivity¹⁶.
        • grade: we grade the cancer more or less by the Broders system (grade I...well differentiated, cancer departs mildly from normal tissue features; grade II...departs moderately; grade III...departs severely and/or is solid).
        • Molecular groups:
          • Group #1: chromosome instability pathway, standard, ordinary, 5FU-responsive CRC marked by aneuploidy, "budding" infiltration at the tumor border and microcomedo-like necrosis of polys within tumor lumens. If these H&E findings not seen and not IEL rich, then think of groups #3 & #4.
          • Group #2: MSI (MSI-H) serrated pathway, MLH1 negative due to methylation, good prognosis, 5FU nonresponder (may even worsen) CRC marked by diploidy, tumor epithelium IELs rich.
          • Group #3: MYH pathway, poor prognosis CRC marked by diploidy & MSI-L.
          • Group #4: CpG island methylation pathway, good prognosis, younger age & HNPCC type with MLH1 (and several other possible markers) negativity by deletion. Use Amsterdam criteria for HNPCC and Bethesda criteria for HNPCC to help determine likelihood of this group.
        • staging tips: is now most commonly by the AJCC TNM system (at NCCN, colon cancer, staging); Dukes system is out-dated. If cancer invades through serosa, staging goes from pT3 to pT4 with implication of adjuvant possible need for radiation & chemo; it may make a difference if the serosal penetration is "free" vs. "sealed off" inside of down inside of an adhesion [L07-9096]. A good schematic portrayal of colorectal staging is HERE.
        • high risk: high risk cases are those that are (1) grade III (solid growth), or (2) node positive, or (3) pT3 or worse, or (4) show definite lymphovascular invasion⁷, or (5) show increased tumor cell invasive "budding"⁷ (budding assoc. /w likely vascular invasion⁸), or breach the serosa. Hi risk indicates need for consideration of adjuvant chemo & radiation.
        • neoadjuvant chemo & XRT for rectal: we see amazing preoperative reductions in rectal tumor size [LMC-03-2461].
      • small-cell carcinoma (rare and commonly associated with an adenomatous polyp and usual have distant mets at time of diagnosis, even if small) [S-01-3682].
      • medullary: tend to be big, right sided, expansile growth pattern /w dense peritumoral lymphoid, , diploid DNA, and slow to metastasize & better prognosis (differentiate this from routine poorly diff. adenoca.)³.
      • rendering an opinion of sporadic CRC vs. hereditary CRC, an algorhythm.
      • cancers and hereditary nonpolyposis colorectal cancer (HNPCC) .
      • serrated adenocarcinoma: serrated architecture, eosinophilic epithelium, and abundant mucous and arise from SA or SSP/SSA^5,9.
    • carcinoid tumor, malignant (there are ordinary and mucinous variants).
    • sarcoma
      • GIST:
        • specific IHC marker CD117 positive².
        • may be a tumor of the "interstitial cells of Cajal"².
        • roughly tend to be "myoid"  or "neural" (GANT...gastrointestinal autonomic nerve tumor) and there are at least two classification systems: Suster and Rosai².
        • behavior differs somewhat in different GI sites¹.
        • ASCO meeting in San Francisco, 13 May '01: report that Gleevec has some striking cure rates ^[newspaper].
        • favorable response to STI571².
      • other traditional sarcomas.
    • lymphoma:
      • MALT-type...low-grades arising primarily in the GI tract organ.
      • large B-cell lymphoma.
      • those secondarily affecting GI.
  • Other intestine-associated obstructing or mass lesions:

1. 4 May 2001, S. P. Seminar in Pittsburgh...lecture and seminar notes.
2. Cancer Control, J. of the Moffitt Cancer Center, 8(3):252-261.
3. Wang L, et. al., [med. colon ca.] Arch. Path. & Lab. Med.129(1):113-4, January 2005.
4. Lewin D, Issues with Adenomatous Polyps, MUSC McKee-PT Seminar, 6 April 2005.
5. Batts KP, Serrated Colorectal Polyps: New Challenges to Old Dogma, [2004 Rodger C. Haggitt Gastrointestinal Pathology Society address] @ USCAP website 5/05.
6. Fenoglio-Preiser CM, et. al., Gastrointestinal Pathology, an Atlas and Text, 2nd Ed.1999 (JBC).
7. Prail F, et. al., Tumor Budding as Prognostic Factor in Stage I/II Colorectal Carcinoma, Histopathology 47(1)17-24, 2005 (EBS' office).
8. Shinto E, et. al., A Novel Classification of Tumor Budding in Colorectal Cancer Based on the Presence of Cytoplasmic Pseudo-fragments Around Budding Foci. Histopathology 47(1):25-31, 2005 (EBS' office).
9. Higuchi T, et. al., Demographic and Pathological Characteristics of Serrated Polyps of Colorectum, Histopathology 47(1):32-40, 2005 (EBS' office).
10. Snover DC, Jass JR, Fenoglio-Preiser C, & Batts KP, Serrated Polyps of the Large Intestine, AJCP (3)124:380-391, Sept. 2005.
11. Longacer & Fenoglio-Preiser, AJSP 14(6):524-537, 1990.
12. AJSP 23(9):1158-1160, 1999.
13. Torlakovic & Snover, Gastroent. 110(3):748-55.
14. Odze, Goldblum, Crawford, Surg. Path. of the GI Tract, Liver, Biliary Tract, and Pancreas, 1067 pages, 2004 [EBS's office].
15. Rex DK, Ulbright TM, & Cummings OW, "Coming to Terms with Pathologists Over Colon Polyps with Cancer or High Grade Dysplasia", J. Clin. Gastroenterology 39(1):1-3, January 2005.
16. Puppa G, et. al., "Pathological assessment of pericolonic tumor deposits in advanced colonic carcinoma: relevance to prognosis and tumor staging ", Modern Pathology 20:843–855, May 2007.

(posted 9 February 2002; latest addition 24 August 2008)