Tumori Grosso Intestino

COLON AND RECTUM TUMOURS

Avvertenza per gli studenti del corso di Anatomia Patologica del corso Integrato Malattie dell’apparato Gastroenterico e

Infettive.

Questi appunti sono solo una traccia di ciò che ho svolto a lezione. Non possono e non vogliono sostituire la trattazione degli stessi argomenti sui libri di testo e non esimono dallo

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singolo studente.

Buon studio

Achille PICH

Colon and rectum tumoursWHO Histological

classification

Epithelial tumours BenignMalignant

Non-epithelial tumours BenignMalignant

Malignant lymphomas

Secondary tumoursPolyps

Adenoma

WHO histological classification

Epithelial tumours

• Tubular• Villous• Tubulovillous

Intraepithelial neoplasia (dysplasia) associated with chronic inflammatory diseases - Low-grade glandular intraepithelial neoplasia - High-grade glandular intraepithelial neoplasia

• Serrated

Epithelial tumours

Carcinoma• Adenocarcinoma• Mucinous adenocarcinoma• Signet-ring cell carcinoma• Small cell carcinoma• Squamous cell carcinoma• Adenosquamous carcinoma• Medullary carcinoma• Undifferentiated carcinoma


Epithelial tumours

Carcinoid (well differentiated endocrine neoplasm)

• EC-cell, serotonin-producing neoplasm

• Others

• L-cell, glucagon-like peptide and PP/PYY producing tumour

Mixed carcinoid-adenocarcinomaOthers


• Lipoma• Leiomyoma• Gastrointestinal stromal tumour• Leiomyosarcoma• Angiosarcoma• Kaposi sarcoma• Malignant melanoma• Others

Non-epithelial tumours


Malignant Lymphomas

• Marginal zone B-cell lymphoma of MALT type

• Burkitt lymphoma

• Others

• Diffuse large B-cell lymphoma

• Burkitt-like / atypical Burkitt-lymphoma

• Mantle cell lymphoma


Secondary tumours

Polyps• Hyperplastic (metaplastic)• Peutz-Jeghers• Juvenile


Adenoma


classificationEpithelial tumoursBenign

TubularVillous

TubulovillousSerrated

POLIPI DEL GROSSO INTESTINO

1.1. ADENOMA TUBULARE ADENOMA TUBULARE (POLIPO ADENOMATOSO)(POLIPO ADENOMATOSO)

Predisposizione familiare.Predisposizione familiare. Unico o multiplo. Peduncolato o sessile. Unico o multiplo. Peduncolato o sessile. Spesso (30%) con aree villose.Spesso (30%) con aree villose. Probabilità di cancerizzazione: Probabilità di cancerizzazione: 5%. 5%. Grado di atipia: lieve, moderata, grave (ca. in situ)Grado di atipia: lieve, moderata, grave (ca. in situ)

2. POLIPOSI FAMILIARE

Ereditaria, Dominante (Mutazione di APC sul cromosoma 5q21).Interessa anche lo stomaco e/o ileo.Il numero dei polipi (adenomatosi) è > 100.Elevata attività proliferativa della mucosa intestinale.Probabilità di cancerizzazione: altissima (quasi sempre).Tv. associata ad epatoblastoma, MEN, angiofibroma rinofaringeo, e ad aumentato rischio di ca. tiroideo e/opancreatico.

3. SINDROME DI GARDNER Malattia familiare.

Polipi adenomatosi multipli (tv. anche nello stomaco e/o ileo)

+ Osteomi multipli + Cisti cornee + Fibromatosi.

Probabilità di cancerizzazione: altissima (quasi sempre).

4. SINDROME DI TURCOT Polipi adenomatosi + tumori cerebrali (glioblastoma). Trasmissione ereditaria recessiva. Mutazione del gene APC o del mismatch-repair gene.

Adenoma



TubularVillous


5. ADENOMA VILLOSO

- Sessile

- Tv. Perdita di proteine (sindrome

proteinodisperdente)

- Probabilità di cancerizzazione: 30-70%

Adenoma



TubularVillous



classification

Polyps– Hyperplastic (metaplastic)

– Peutz-Jeghers– Juvenile

6. POLIPO IPERPLASTICO (METAPLASTICO)

Sessile Piccolo (per lo più < 5mm) Molto frequente: nel 30-50% degli adulti. Non è una neoplasia.


classification


– Peutz-Jeghers

– Juvenile

7. POLIPO GIOVANILE (DA RITENZIONE)

Solitario Nei bambini Tv. autoamputazione Non è una vera neoplasia

7c. SINDROME DI CRONKHITE - CANADA Non ereditaria. Polipi giovanili multipli + alopecia, atrofia ungueale, e/o iperpigmentazione. Possono insorgere adenomi tubulari e carcinomi colo-rettali.

7b. POLIPOSI GIOVANILE MULTIPLA Può essere rischiosa per la vita. Può associarsi ad adenomi tubulari ed adenocarcinomi dello stomaco, duodeno, grosso intestino e pancreas.


classification


– Peutz-Jeghers– Juvenile

9. SINDROME DI COWDEN Malattia autosomica dominante (mutazione gene PTEN/MMAC1). Polipi amartomatosi multipli + trichilemmomi faciali, cheratosi acrale, papillomi orali. Elevata incidenza di neoplasie in varie sedi.

8. POLIPO DI PEUTZ - JEGHERS Amartoma. Nella forma multipla (poliposi di Peutz-Jeghers) può interessare anche lo stomaco e il piccolo intestino.

Cancerizzazione dei polipi

Relationship with carcinoma1) Solitary hyperplastic polyps (which represent the large majority of epithelial colonic polyps), retention polyps, and Peutz-Jeghers polyps do not become malignant.

2) Patients with any type of polyposis syndrome are at increased risk for the development of large bowel carcinoma. This incidence is extremely high (nearly 100%) in familial polyposis and Gardner's syndrome; it is lower, but still increased, in patients with Peutz-Jeghers syndrome, juvenile polyposis, and hyperplastic polyposis.

3) Villous adenomas can become malignant, in a high proportion of cases (29% to 70%).

4) Adenomatous polyps can become malignant in about 5%.

The malignant transformation of polyps (so-called adenoma-carcinoma sequence) has been carefully documented with chemically induced colorectal tumors in animals by the demonstration that the morphologic progression from adenomatous polyp with mild to moderate to severe atypia ("carcinoma in situ") and to invasive and metastatic carcinoma is accompanied by (and presumably caused by) a series of molecular alterations. These alterations include the mutational activation of oncogenes and the inactivation of tumor-suppressor genes.

It is thought that mutations in at least four or five genes are required to produce a fully malignant phenotype. These include activational mutation of the ras oncogene, mutations of the p53 gene (located on chromosome 17), deletion of the dcc ("deleted in colonic carcinoma") gene (located on chromosome 18), and possibly mutations of the mcc ("mutated on colonic carcinoma") gene (located on chromosome 5). In familial polyposis, an additional (and very early) change is a mutation of the apc (adenomatous polyposis coli) gene (located on chromosome 5).

Treatment1) Solitary juvenile polyps. Simple removal is sufficient.

2) Familiar polyposis. Since all untreated patients eventually develop carcinoma of the colon, colectomy is indicated even though the patient is young.

3) Villous adenomas. Should be removed in toto; colon resection is sometimes necessary.

4) Adenomatous polyps. Solitary adenomatous polyps are routinely removed endoscopically. When several polyps are present, the patient can be safely managed by removing these polyps individually rather than performing a partial or total colectomy.

5) Adenomatous polyp with area of carcinoma.

a) The carcinomatous glands may be present only in the mucosa and lamina propria above the muscularis mucosae ("carcinoma in situ").This situation has never been found associated with lymph node metastases

simple polypectomy

b) They may extend beyond the muscularis mucosae but not invade the stalk of the polyp ("focal carcinoma")The incidence of lymph node metastasis is less than 1%.

simple polypectomy (unless the lesion is undifferen-tiated or is accompanied by obvious vascular invasion).

c) They may extend to the base of the stalk or beyond ("focal carcinoma with stalk invasion"). The possibility of lymph node metastases, although still relatively low, is probably high enough to justify a

formal bowel resection, especially when the carcinoma is found in the submucosa of the underlying colonic wall and/or when it is present at the surgical margin.


classificationEpithelial tumours

Malignant

Carcinoma– Adenocarcinoma– Mucinous adenocarcinoma– Signet-ring cell carcinoma– Small cell carcinoma– Squamous cell carcinoma– Adenosquamous carcinoma– Medullary carcinoma– Undifferentiated carcinoma

EPIDEMIOLOGIA

Circa 875.000 casi di carcinoma del colon-retto nel 1996, rappresentanti l’ 8.5% di tutti i nuovi carcinomi.

Incidenza (nuovi casi per 100.000 per anno):

- 44 (USA, Australia: età media 62 anni)- 35.6 Europa occidentale- 28 Argentina,Cile- 24.8 Europa orientale ed ex URSS- 17.5 Brasile- 13.3 Cina- 5.7 Africa- 2.7 Medio Oriente, India, Asia Sud Orientale

EZIOLOGIA

1) Dieta e stile di vita

Fattori di rischio: • Alimentazione ipercalorica e vita sedentaria • Consumo di carne • Fumo e alcool

Fattori protettivi: • Consumo di vegetali • Antiinfiammatori non-steroidei • Terapia sostitutiva estrogenica • Attività fisica • Dieta ricca di fibre (?)

2) Infiammazioni croniche Colite ulcerosa • (incidenza: x20) Malattia di Crohn • (incidenza: x3)

3) Pregressa irradiazione pelvica

4) Pregressa uretero-sigmoidostomia

5) Fattori genetici elevatissima predisposizione per il carcinoma nella • Poliposi familiare (100%) • Sindrome di Lynch (50%) • Sindrome di Torre-Muir

LOCALIZZAZIONE

About 50% of all carcinomas occur in the rectosigmoid area, although their relative incidence seems to be decreasing.

A shift in location toward the proximal colon during the past few decades has been noted. Right-sided tumors are said to be more common in the elderly, in blacks, and in patients with diverticular disease.

Multicentric carcinomas are found in 3% to 6% of the cases.

ASPETTO MACROSCOPICO

Most colorectal carcinomas can be described as either polypoid or ulcerative/infiltrating.

• Polypoid: a bulky mass with well defined, rolled margins and a sharp dividing line with the normal bowel.

• Ulcerative/infiltrating: has a less elevated surface and is centrally ulcerated.

A particular variant of this tumor type is referred to as "flat" or "depressed" carcinoma and is thought to arise de novo rather than through malignant transformation of an adenoma.

ASPETTO MICROSCOPICO Usually is a well to moderately differentiated adenocarcinoma secreting variable amounts of mucin.

The tumor cells represent a combination of columnar and goblet cells, with occasional participation of endocrine cells and the exceptionally Paneth cells.

Often there is an inflammatory and desmoplastic reaction, particularly prominent at the edge of the tumor. Most of the inflammatory cells are T lymphocytes, but B lymphocytes, plasma cell, histiocytes, and S-100 proteinpositive dendritic cells may also be present.

The tumor may be seen invading all the layers of the bowel and extending into the pericolic fat, permeating perineurial spaces, and invading veins.

HISTOLOGICAL GRADING

G1

G2

G3

Well differentiated(glandular structures in >95%)

Moderately differentiated(glandular structures in 50-95%)

Poorly differentiated (glandular structures in 5-50%)G4 Undifferentiated (glandular structures in <5%) • Mucinous and signet ring cell type • Medullary type

Carcinomas of the large bowel may present with rectal bleeding, changes in bowel habits (such as diarrhea alternating with constipation), anemia resulting from chronic blood loss, and vague abdominal pain. Intestinal obstruction is common when the tumor is situated in the left colon and rare for tumors in the cecum or ascending colon.

One of four cecal carcinomas will present with signs suggestive of appendicitis.

Perforation may rarely occur, either at the site of the carcinoma or in the cecum as a result of distention caused by an obstructing rectosigmoid carcinoma.

Unfortunately, the previously mentioned symptoms are often indicative of advanced disease.

CLINICAL FEATURES

To detect tumors at an earlier stage, one can perform appropriately timed proctosigmoidoscopic examinations of both men and women over 40 years of age; such examinations should detect about 50% of the cases. Whether routine examination of the entire large bowel with the fiberscope will prove rewarding as a screening method remains to be seen.

Routine barium enemas are too expensive and not entirely without risk.

Guaiac stool examination for occult blood is an efficient and inexpensive way of detecting cases of early, asymptomatic carcinoma.

DIAGNOSIS

Carcinoembryonic antigen (CEA) has been detected in the serum of 72% to 97% of patients with colorectal carcinoma. It disappears after resection of the tumor and reappears in the event of recurrence or metastases. Higher values are found in tumors that have spread beyond the bowel wall, in poorly differentiated neoplasms, and in tumors associated with blood vessel, lymphatic, and perineural invasion.

Elevated circulating levels of CEA also occur in carcinomas of the stomach, pancreas, breast, and prostate gland.

Unfortunately, the test is often negative during the early stages of colorectal carcinoma and is therefore not a good screening procedure. Its main utility has been in the monitoring of therapy and in the early detection of metastases.

CEA can also be detected in the tumor tissue by immunocytochemistry, radioimmunometric assay, or enzyme immunometric assay; its ability to discriminate between normal and carcinomatous tissue is higher than that of CA 19-9, CA 125, and CA 195, these being other antigens that have been found to be associated with colorectal carcinoma.

A novel and very promising screening approach is that of searching for ras oncogene mutations in the stools; unfortunately, the test does not distinguish polyps from carcinoma.

Cytology is of little practical value. In 87 patients with carcinoma the malignancy was correctly identified in seventy (80%); the incidence of false positives in 438 patients was 0.45%; however, the technique employed to obtain the specimen—which involves extensive cleansing of the colon followed by a diagnostic enema with manipulation of the patient—has led to an unenthusiastic response from clinicians.Low-lying rectal lesions can be easily sampled.

Brush cytology can also be performed via the fiberoptic scope. It is a sensitive technique, but it has not yet found widespread acceptance.

Cytology

A positive biopsy should always be obtained before radical surgery for colorectal carcinoma is undertaken. It is imperative that sufficient representative material be taken.

In large lesions, it is advisable to perform several biopsies from diverse areas.

Lesions below the peritoneal reflection should be removed in toto wherever possible to facilitate their orientation for section by the pathologist. Sometimes is more difficult (but just as critical) to ascertain the position and extent. Close communication with the endoscopist and surgeon, intact biopsy of an adequate size and depth, and proper orientation of the specimen are essential requisites for this determination.

Biopsy

IMMUNOISTOCHIMICA

Keratin Colorectal adenocarcinomas are invariably positive for keratin (positivity for CK 20 and negativity for CK 7).

CEA Reactivity for CEA is also the rule; as a matter of fact, failure to demonstrate CEA in an adenocarcinoma makes it unlikely that the tumor is primary in the large bowel. There is good correlation of the immunohistologic pattern with the serum levels but not with tumor staging or degree of differentiation.

Tumor-associated glycoprotein (TAG-72), recognized by MoAb B72.3, is present not only in 100% of invasive colorectal carcinomas but also in the majority of hyperplastic and adenomatous polyps and even in normal mucosa, but with variable pattern of expression. Another tumor-associated antigen, large external antigen (LEA), has been identified in the tumor tissue and sera of colorectal carcinoma cases. Carcinomas of the large bowel often show loss of blood group isoantigens and of HLA-A, B, and C expression, particularly if poorly differentiated and acquire reactivity for blood group substance H. Immunoreactivity for the secretory component of immunoglobulin is seen in about 50% and is particularly strong in the well-differentiated tumors.

p53 mutations have been detected by molecular techniques in the majority of colorectal carcinomas. About half of the tumors show positive staining; regardless of site, differentiation, or DNA ploidy.

Mutations of the ras oncogene have been found in a minority of colorectal carcinomas, particularly those in the metastatic group.

Enhanced expression of the c-myc oncogene occurs in about 90% of colorectal carcinomas.

The proliferative activity of colorectal carcinoma can be measured by S-phase determination, staining for Ki-67 or PCNA, and AgNOR counts. None of these determinations correlate very closely with microscopic grade, and they may carry prognostic implications of their own.

Villin, a cytoskeletal protein associated with the axial microfilament bundles of brush border microvilli, is consistently expressed regardless of differentiation. Increased expression of cathepsin B (a lysosomal cysteine proteinase) is also a feature of these tumors, particularly in advanced stages of the disease. Expression of the epithelial-specific adhesion molecule E-cadherin is closely related to the degree of tumor differentiation. A high percentage of colorectal carcinomas are immunopositive for HCG, particularly mucinous and poorly differentiated tumors. Placental alkaline phosphatase (PLAP) has been detected in about 10% of all colorectal carcinomas.

TNM Clinical Classification

TX Primary tumour cannot be assessedT0

Submucosa

T2 Muscularis propria

T3 Tumour invades subserosa or into non-peritonealized pericolic or perirectal tissues

T4 Tumour directly invades other organs or structures and/or perforates visceral peritoneumT4a Tumour perforates visceral peritoneumT4b directly invades other organs or structures

T - Primary Tumour

No evidence of primary tumour

T1Tis Carcinoma in situ: intraepithelial or invasion

of lamina propria


N0 No regional lymph node metastasisN1 Metastasis in 1 to 3 regional lymph nodes

N - Regional Lymph Nodes

NX Regional lymph nodes cannot be assessed

N1a Metastasis in 1 regional lymph nodeN1b Metastasis in 2-3 regional lymph nodesN1c Tumour deposit(s) (satellites) in the subserosa or in non-peritonealized pericolic or perirectal soft tissue without regional lymph node metastasis


M0 No distant metastasisM1

M - Distant MetastasisMX Distant metastasis cannot be assessed

N2 Metastasis in 4 or more regional lymph nodesN2a Metastasis in 4-6 regional lymph nodesN2b Metastasis in 7 or more regional lymph nodes

Distant metastasisM1a Metastasis confined to one organ (liver, lung, ovary, non-regional lymph node(s))M1b Metastasis in more than one organ or the peritoneum

STAGE GROUPING(1)

Stage I

Stage II

Stage IIC

T1,T2

T3,T4

T3

T4b

N0

N0

N0

N0

M0

M0

M0

M0

Stage 0 Tis N0 M0

Stage IIA

T4a N0 M0Stage IIB

STAGE GROUPING(2)

Stage IIIA

Stage IIIB

Stage IIIC

Stage IVA

T1,T2T1T3,T4aT2,T3

T4a

Any T

N1N2aN1N2a

N2a

Any N

M0M0M0M0

M0

M1a

Stage III Any T N1,N2 M0

T4b N1,N2 M0

T1,T2 N2b M0

T3,T4a N2b M0

Stage IVB Any T Any N M1b

Flat carcinomas have a greater tendency for deep stromal invasion with lymphovascular permeation than the more common polypoid types.

The most common sites of metastatic involvement of colorectal carcinoma are regional lymph nodes and liver. Lymph node metastases are more common in the tumors showing poorly differentiated areas and a highly infiltrative pattern of growth.

Liver metastases are more common in the tumors showing evidence of blood vessel invasion. Other relatively common metastatic sites include peritoneum, lung, and ovaries.

Rare metastatic sites include central nervous system, bone, testis, uterus, and oral cavity.

SPREAD AND METASTASIS

The standard therapy for colorectal carcinoma is surgical resection:

- ileocolectomy (carcinoma of the cecum or ascending colon), - abdominoperineal resection (tumour located below the peritoneal reflection) - anterior resection (tumors in other areas)

The current resectability rate for colorectal carcinoma is 92%, and the operative mortality for resections for cure is 2%.

TREATMENT

Fulguration, endoscopic transrectal resection, and fullthickness local excision are acceptable alternative procedures for rectal carcinomas if the tumor is small, superficial, and well differentiated and/or if the patient is a poor candidate for abdominoperineal resection.

The possible role of preoperative or postoperative irradiation and/or chemotherapy for operable carcinoma of the large bowel is still questionable.

The 5-year crude survival rate after curative resection for colorectal carcinoma ranges between 40% and 60% in most large series. Local recurrence and/or regional lymph node metastases occur in over 90% of the failure cases, and they represent the only site of tumor in about half of them. A total of 71% of the recurrences are evident within the first 2 years and 91% by 5 years.

PROGNOSIS

PROGNOSTIC FACTORS

1. Age. Tumors occurring in very young and very old patients are associated with a poor prognosis.

2. Sex. The prognosis is significantly better for females than for males.

3. Location. This factor remains controversial.

4. Multiplicity of tumors. The survival rate for patients with synchronous or metachronous malignancy of the large bowel is similar to that for patients with solitary colorectal carcinoma.

5. Local extent.

6. Size: is not a reliable prognostic indicator.

7. Obstruction.

8. Perforation: is linked to a poor prognosis.

9. Microscopic type and grade. There is a definite relationship between the microscopic grade of the tumor and its prognosis. Among the microscopic subtypes, mucinous carcinoma, small cell carcinoma, and signet ring carcinoma have a worse prognosis than the ordinary type of adenocarcinoma.

10. HLA-DR expression. Tumors having strong HLA-DR expression have the best survival, even within the same Dukes' stage.

11. Tumor margins. Carcinomas having pushing margins and an inflammatory infiltrate (plasma cells and lymphocytes) have a better prognosis.

12. Inflammatory reaction.

13. Vascular and perineurial invasion: negative prognosis.

14. Lymph node involvement.

15. Dukes' staging. The 5-year survival rates are 90% or higher for Dukes' A, 50% to 65% for Dukes' B, and 15% to 25% for Dukes' C.

16. DNA ploidy: several studies have shown a correlation between aneuploidy and risk of recurrence or survival.

17. Cell proliferation.

18. Allelic loss of chromosome 18q: negative prognostic significance.

19. Oncogene expression. K-ras mutations and overexpression of the ras p21 protein are associated with recurrent disease. p53 overexpression was found to be an independent predictor of survival. Expression of the c-myc oncogene has been found to correlate with the degree of differentiation of the tumor.



Malignant


Large lakes of extracellular mucin, mixed with collections of tumor cells, that constitute at least half of the tumor mass.

Mucinous tumors usually have an exophytic shape, comprise 15% of colorectal carcinomas and occur most commonly in the rectum. In 31% were associated with villous adenomas, 7% with ulcerative colitis, 8% with colitis, and 5% with prior pelvic irradiation. Mucinous carcinomas are also more frequently associated with adenomas and tend to present at a more advanced stage.

Their prognosis is somewhat worse than for the conventional type of adenocarcinoma, at least when they are located in the rectum and/or if they are stage B lesions.

Mucinous carcinoma



Malignant


Rare form of colorectal malignancy that usually affects young patients.

It usually presents grossly as a diffuse infiltration of the wall. Microscopically, the tumor grows in a diffuse fashion, with little if any glandular formation. Most or all of the mucin is intracellular and displaces the nucleus with a typical signet ring configuration of the cells.

Metastases tend to develop in lymph nodes, the peritoneal surface, and the ovary rather than the liver. The pattern of spread is mainly in the form of peritoneal dissemination. The prognosis is extremely poor.

The possibility of the colorectal lesion representing a metastasis from a gastric primary lesion should always be investigated.

Signet-ring cell carcinoma



Malignant


Tumor having a microscopic appearance similar to that of its pulmonary homonym, with few M.E. dense-core secretory granules in the cytoplasm, and IHC positivity for neuron-specific enolase and other endocrine markers, such as synaptophysin.

The entire tumor may have this appearance, or there may be foci of glandular or squamous. Most small cell carcinomas of the large bowel are located in the right colon.

The prognosis is poor, with early metastases to lymph nodes and liver.

Small cell carcinoma



Malignant


Squamous differentiation may be present in colorectal carcinoma; this is more common in cecal neoplasms but may be seen in any other area of the large bowel.

In most instances, the squamous component is associated with glandular elements (adenosquamous carcinoma) but occasionally it is seen in a pure form (squamous cell carcinoma).

An association has been noted between squamous changes in colorectal carcinoma and ulcerative colitis. For the squamous tumors located in the low rectum, the alternative possibility of upward extension or submucosal metastasis from a carcinoma of the anal canal should be considered.

Adenosquamous carcinoma



Carcinoid– EC-cell, serotonin-producing neoplasm

– Others

– L-cell, glucagon-like peptide and PP/PYY producing tumour

Mixed carcinoid-adenocarcinomaOthers

(well differentiated endocrine neoplasm)

Carcinoids are more common in the rectum.

In the colon they tend to be large, extend deeply through the wall of the bowel, and involve the regional lymph nodes.

In the rectum, they are often located in the anterior or lateral wall. Most measure less than 0.5 cm in diameter. Only very few, larger than 2 cm, are associated with lymph node metastases. Rectal carcinoids have been reported in bowels affected by ulcerative colitis or Crohn's disease and were multicentric. They have also been reported in association with ovarian carcinoid.

Colorectal carcinoids are practically never associated with the carcinoid syndrome.

Grossly, carcinoid may appear as a flat and slightly depressed plaque or as a polypoid lesion. One of its most distinctive features is the yellow color that it acquires after formalin fixation.

.

Microscopically, invasion of the stroma by small uniform cells growing in a ribbon or festoon fashion is seen. A minor tubular and/or acinar component associated with mucin production may also be present.

Argentaffin and argyrophil reactions are said to be usually negative, but consistently positive Grimelius stain has been reported by several authors.

Immunocytochemically, they stain for the panendocrine markers (neuron-specific enolase (NSE), chromogranin, synaptophysin) and for a variety of peptide hormones. The most common are somatostatin, glucagon, substance P, and peptide YY (usually absent in other sites), but gastrin-colecystokinin, calcitonin, pancreatic poly-peptide, and motilin have also been demonstrated.

Many of the tumors are polyhormonal.

Rectal carcinoids may also be positive for CEA, HCG, and prostatic acid phosphatase (PAP).

The PAP positivity is of practical importance because metastatic prostatic carcinoma may be suspected; however carcinoid is consistently negative for prostatic specific antigen.

Rectal carcinoid tumors smaller than 2 cm and limited to the mucosa or submucosa are best treated by local excision; those of larger size and/or exhibiting invasion of the muscularis externa need radical surgery, in view of their propensity for lymph node involvement.

In one study, all of the 19 nonmetastasizing carcinoid tumors showed a diploid pattern by flow cytometry, whereas all three metastasizing tumors were aneuploid. If this remarkable correlation is confirmed, DNA ploidy analysis may become important in this situation to decide on the extent of the operation.

TREATMENT AND PROGNOSIS

ASPETTI CLINICI DELLA SINDROME DA CARCINOIDE

1. Disturbi vasomotori Flushes cutanei e cianosi evidente (nella maggior parte dei pazienti)

2. Ipermotilità intestinale Diarrea, crampi, nausea, vomito (nella maggior parte dei pazienti)

3. Attacchi asmatici broncocostrittivi Tosse, sibili, dispnea (in un terzo dei pazienti)

4. Epatomegalia nodulare, correlata a metastasi epatiche (in alcuni pazienti)

5. Fibrosi sistemica

Interessamento cardiaco Ispessimento e stenosi valvolare tricuspidale e polmonare

Fibrosi endocardiaca, principalmente nel ventricolo destro (nei carcinoidi bronchiali è interessato quello sinistro)

Fibrosi retroperitoneale e pelvica

Placche collagene della pleura e dell’intimadell’aorta

– Leiomyoma– Gastrointestinal stromal tumour– Leiomyosarcoma– Angiosarcoma– Kaposi sarcoma– Malignant melanoma– Others


Colon and rectum tumoursWHO Histological classification

– Lipoma

– Lipoma

– Gastrointestinal stromal tumour– Leiomyosarcoma– Angiosarcoma– Kaposi sarcoma– Malignant Melanoma– Others


– Leiomyoma


– Lipoma– Leiomyoma– Gastrointestinal stromal tumour – Angiosarcoma– Kaposi sarcoma– Malignant Melanoma– Others


– Leiomyosarcoma


– Lipoma– Leiomyoma– Gastrointestinal stromal tumour – Angiosarcoma– Kaposi sarcoma– Malignant melanoma– Others


– Leiomyosarcoma


– Lipoma– Leiomyoma– Gastrointestinal stromal tumour – Angiosarcoma– Kaposi sarcoma– Malignant Melanoma


– Leiomyosarcoma


– Others


Malignant Lymphomas– Marginal zone B-cell lymphoma of MALT type

– Burkitt lymphoma

– Others

– Diffuse large B-cell lymphoma

– Burkitt-like / atypical Burkitt-lymphoma

– Mantle cell lymphoma

Malignant lymphomas are less frequent than in the small bowel or stomach. Some of the cases of large bowel lymphoma have been seen in renal transplant recipients or in patients with ulcerative colitis. These tumors can occur at any level of the colorectum.

Grossly, they may produce prominent mucosal folds, prominent ulceration, a large mass, or a solitary polyp, multiple small polyps distributed throughout the colorectum that may also extend to the small bowel ("lymphomatous polyposis").

The regional lymph nodes are involved in about half of the cases.

They are nearly always of non-Hodgkin's type; the large cell and small cell types are the predominant varieties.

The low-grade tumors have features similar to the group of MALT lymphomas. They often show evidence of plasmacytic differentiation; when this is extensive and associated with abundant immunoglobulin production (and occasionally also with amyloid deposits), the designation of plasmacytoma has sometimes been used for them.

The MALT concept Mucosa-associated lymphoid tissue (MALT) is the term proposed by Isaacson et al. for the component of the immune system that has evolved to protect the freely permeable surface of the gastrointestinal tract and other mucosal membranes directly exposed to the external environment.

This comprises lymphoid nodules (which in the ileum form the Peyer's patches), lymphocytes and plasma cells in the lamina propria, and intraepithelial lymphocytes.

The lymphomas arising from it ("MALTomas") have propensity to involve other mucosal sites, which has been explained by the normal homing pattern of MALT lymphocytes.

Lymphomatoid polyposis, which is nearly always composed predominantly of small cleaved cells and represents the colorectal manifestation of mantle cell lymphoma, may evolve into a high-grade lymphoma.

Other reported types of colorectal hematolymphoid malignancies include mantle cell lymphoma, anaplastic large cell lymphoma, AILD like lymphoma, and true histiocytic lymphoma.


classification

Secondary tumours

Metastatic tumors occur as a part of a disse-minated process.

These tumors form disk-like areas in which there is a central area of ulceration; the normal mucosa extends to the ulcer, giving indirect evidence that the metastatic focus began in the submucosa. This phenomenon is particularly common in malignant melanoma and primary carcinoma of the lung.

Prostatic carcinoma can extend into the

rectum and simulate a primary rectal neoplasm.

PSA positive immunostaining in prostate

carcinoma allows the differential diagnosis.

Tumori Grosso Intestino

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