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2006 7:53 Page 93

CHAPTER 5

Tumours of the Appendix

The appendix is the most frequent site of carcinoids,


i.e. tumours with endocrine differentiation, that span a wide
range of morphological variety.

Adenocarcinomas of the appendix also show interesting mor-


phological variations, from those that resemble the usual
colorectal carcinoma to those that arise from a carcinoid and
to mucinous tumours that may appear well differentiated and
indistinguishable from adenoma and yet spread widely
through the peritoneal cavity.
05 19.7.2006 7:53 Page 94

WHO histological classification of tumours of the appendix1


Epithelial tumours Non-epithelial tumours
Adenoma 8140/02 Neuroma 9570/0
Tubular 8211/0 Lipoma 8850/0
Villous 8261/0 Leiomyoma 8890/0
Tubulovillous 8263/0 Gastrointestinal stromal tumour 8936/1
Serrated 8213/0 Leiomyosarcoma 8890/3
Kaposi sarcoma 9140/3
Carcinoma Others
Adenocarcinoma 8140/3
Mucinous adenocarcinoma 8480/3 Malignant lymphoma
Signet-ring cell carcinoma 8490/3
Small cell carcinoma 8041/3 Secondary tumours
Undifferentiated carcinoma 8020/3
Hyperplastic (metaplastic) polyp
Carcinoid (well differentiated endocrine neoplasm) 8240/3
EC-cell, serotonin-producing neoplasm 8241/3
L-cell, glucagon-like peptide
and PP/PYY producing tumour
Others
Tubular carcinoid 8245/1
Goblet cell carcinoid (mucinous carcinoid) 8243/3
Mixed carcinoid-adenocarcinoma 8244/3
Others
______________
1
This classification is modified from the previous WHO histological classification of tumours {845} taking into account changes in our understanding of these lesions. In the case of
endocrine neoplasms, it is based on the recent WHO classification {1784} but has been simplified to be of more practical utility in morphological classification.
2
Morphology code of the International Classification of Diseases for Oncology (ICD-O) {542} and the Systematized Nomenclature of Medicine (http://snomed.org). Behaviour is coded
/0 for benign tumours, /3 for malignant tumours, and /1 for unspecified, borderline or uncertain behaviour.

TNM classification of tumours of the appendix


TNM classification1, 2

T – Primary Tumour M – Distant Metastasis


TX Primary tumour cannot be assessed MX Distant metastasis cannot be assessed
T0 No evidence of primary tumour M0 No distant metastasis
Tis Carcinoma in situ: intraepithelial or invasion of lamina propria3 M1 Distant metastasis

T1 Tumour invades submucosa


T2 Tumour invades muscularis propria
T3 Tumour invades through muscularis propria into subserosa Stage Grouping
or into non-peritonealized periappendiceal tissue
T4 Tumour directly invades other organs or structures Stage 0 Tis N0 M0
and/or perforates visceral peritoneum Stage I T1 N0 M0
T2 N0 M0
N – Regional Lymph Nodes Stage II T3 N0 M0
NX Regional lymph nodes cannot be assessed T4 N0 M0
N0 No regional lymph node metastasis Stage III Any T N1 M0
N1 Metastasis in 1 to 3 regional lymph nodes Any T N2 M0
N2 Metastasis in 4 or more regional lymph nodes Stage IV Any T Any N M1
______________
1
{1, 66}. The classification applies only to carcinomas.
2
A help desk for specific questions about the TNM classification is available at http://tnm.uicc.org.
3
This includes cancer cells confined within the glandular basement membrane (intraepithelial) or lamina propria (intramucosal) with no extension through muscularis mucosae into
submucosa.

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N.J. Carr
Adenocarcinoma of the appendix M.J. Arends
G.T. Deans
L.H. Sobin

Definition with abdominal distension. Rarely, exter- mucocoele, but this is descriptive not a
A malignant epithelial neoplasm of the nal fistulation occurs {251, 393, 707}. pathological diagnosis {250, 251}.
appendix with invasion beyond the mus-
cularis mucosae. Imaging Tumour spread and staging
Ultrasound, computerised tomography Although the TNM classification currently
ICD-O codes (CT) scan or barium enema are of limited uses the same criteria as for colorectal
Adenocarcinoma 8140/3 benefit in the pre-operative diagnosis of tumours, appendiceal cases should be
Mucinous adenocarcinoma 8480/3 cases presenting as acute appendicitis. separately classified. This is particularly
Signet-ring cell carcinoma 8490/3 Ultrasound and CT scan are the pre- important because of the special nature
ferred imaging procedures in cases pre- of pseudomyxoma peritonei, where
Epidemiology senting with abdominal mass or malignant cells may be scarce and acel-
Adenocarcinoma of the appendix occurs pseudomyxoma peritonei {393, 707}. lular mucin may seem to have spread fur-
in 0.1% of appendicectomies, corre- Serial CT scanning and CEA measure- ther than the malignant cells {250}.
sponding to an estimated incidence of ments can assess the extent of peri- Well differentiated mucinous appen-
0.2/100,000 per annum {393, 1928}. toneal involvement and the subsequent diceal adenocarcinomas generally grow
Adenocarcinomas accounted for 58% of course of the disease. Intraepithelial neo- slowly, and typically produce the clinical
malignant appendiceal tumours in the plasia of the appendix may occur con- picture of pseudomyxoma peritonei.
SEER database, the remainder being currently with a carcinoma elsewhere in Lymph node metastases tend to occur
mostly carcinoids. The rates for the car- the large intestine {393}. late. Rarely, tumour growth in the
cinomas stayed constant during the peri- retroperitoneum may produce ‘pseudo-
od 1973-1987 {1928}. The median age of Macroscopy myxoma retroperitonei’ {1194}. The
patients with mucinous and non-muci- In cases of primary adenocarcinoma, the behaviour of non-mucinous carcinomas
nous adenocarcinoma was about 65 appendix may be enlarged, deformed or resembles that of their colonic counter-
years in SEER data; other studies sug- completely destroyed {250, 251, 1612}. parts.
gest a peak age at manifestation in the Well differentiated lesions are often cys-
sixth decade {250, 393}. Males appear to tic and may be called cystadenocarcino- Pseudomyxoma peritonei
be more commonly affected than mas. A grossly appreciated swelling of Pseudomyxoma peritonei is the pres-
females {393}. the appendix due to the accumulation of ence of mucinous material on peritoneal
mucus within the lumen can be termed surfaces. It is not a complete histological
Aetiology
Patients with chronic ulcerative colitis
(UC) have an increased susceptibility to
formation of epithelial dysplasia and
malignancy in affected segments of
bowel; inflammatory involvement of the
appendix is seen in approximately half of
UC cases with pancolitis.
Both adenoma and adenocarcinoma of
the appendix have been described in
patients affected by long-standing ulcer-
ative colitis {1394}.

Clinical features
Signs and symptoms
Many patients with appendiceal adeno-
carcinoma have clinical features indistin-
guishable from acute appendicitis. Most
of the remaining cases present as an
abdominal mass {250, 393}. Spread to
the peritoneal cavity may produce large
volumes of mucus, causing pseudomyx-
oma peritonei. Such cases may present Fig. 5.01 Mucinous adenocarcinoma arising in a villous adenoma. The lumen is lined by a villous adenoma.

Adenocarcinoma 95
05 19.7.2006 7:53 Page 96

A B
Fig. 5.02 Appendiceal mucinous adenocarcinoma. Fig. 5.03 Pseudomyxoma peritonei. A Several loops of bowel are encased in a multilocular mucinous mass.
B Well differentiated mucus producing epithelium embedded in a fibrous matrix; mucus is present within the
lumen and is extravasated into the stroma.

diagnosis in itself; the prognosis will such cases are examples of well differen- mine the extent of invasion, because well
depend on the nature of the causative tiated adenocarcinoma. differentiated carcinomas of the appen-
lesion. Nevertheless, pseudomyxoma Although most cases of pseudomyxoma dix can mimic adenomas by invading on
peritonei is often applied to a distinctive peritonei are due to spread from a pri- a broad front rather than showing infiltra-
clinical picture produced by well differ- mary carcinoma of the appendix, cases tive or single-cell invasion. Conversely, in
entiated mucinous adenocarcinomas in have been reported in association with some adenomas, acellular mucin dis-
which the growth of malignant cells with- mucinous carcinomas of other sites, sects through the wall, mimicking inva-
in the peritoneal cavity causes a slow but including gallbladder, stomach, colorec- sion; this feature may be especially
relentless accumulation of mucin. Cells tum, pancreas, fallopian tube, urachus, prominent if there is inflammation. If there
may be very scanty within this mucinous lung, and breast {346, 612, 707, 981, is acellular mucin in the appendiceal
material. 1199, 2199}. wall, the diagnosis of adenoma should
A distinctive feature of well differentiated Although the ovary has been thought of only be made if the muscularis mucosae
mucinous carcinomatosis is its distribu- as a common primary site {104, 1705}, is intact since this term implies that the
tion in the abdomen. There is a tendency there is an accumulating body of evi- lesion is curable by complete excision.
to spare the peritoneal surfaces of the dence based on immunohistochemistry It is appropriate to use the term muci-
bowel, whereas large-volume disease is and molecular genetics suggesting that nous tumour of uncertain malignant
found in the greater omentum, beneath this is not the case, and that in most potential for neoplasms in which the his-
the right hemidiaphragm, in the right patients with low-grade mucinous tu- tological features do not allow distinction
retrohepatic space, at the ligament of mours of the ovary and appendix with between a lesion that is benign (an ade-
Treitz, in the left abdominal gutter and in pseudomyxoma peritonei the lesions are noma) from one that has the potential to
the pelvis {1854}. In these cases, tumour probably metastatic from an appendiceal cause metastases (an adenocarcinoma).
growth tends to remain confined to the primary {1536, 1611, 1612, 1871, 2187}. The term low-grade mucinous cystic
abdomen for many years. Mucinous tumour has also been used for lesions
cysts within the spleen occur occasional- Histopathology that are histologically not frankly malig-
ly {433}. The majority of appendiceal adenocarci- nant {2187A}.
It has been suggested that appendiceal nomas are well differentiated and muci-
adenomas can cause widespread pseu- nous {250, 706}. If signet-ring cells Grading
domyxoma peritonei with an ultimately account for more than 50% of the neo- Grading is the same as in the large intes-
fatal outcome, and some authors use the plasm, the term signet-ring cell carcino- tine. Some adenocarcinomas of the
term ‘adenomucinosis’ for the spread of ma is appropriate. appendix are so well differentiated that
such lesions through the abdomen {1611, The term mucinous cystadenocarcinoma their neoplastic features may be very
1612}. It is considered more likely that may be used for well differentiated muci- subtle {250}.
nous tumours with cystic structures. How-
ever, this designation is descriptive and
does not constitute a separate disease
entity {251, 2115}.

Diagnostic criteria
The fundamental criterion for making the
diagnosis of adenocarcinoma is the
presence of invasive neoplasm beyond
the muscularis mucosae; this is the same
criterion that is applied throughout the
large intestine (see Table 5.01). However,
Fig. 5.04 Pseudomyxoma peritonei. in practice it is not always easy to deter- Fig. 5.05 Mucocoele of appendix.

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05 19.7.2006 7:53 Page 97

Fig. 5.06 Serrated adenoma of appendix. Fig. 5.07 Serrated adenoma (left) and tubulovillous Fig. 5.08 Adenoma with undulating morphology.
adenoma (right).

Precursor lesions and benign tumours adenocarcinoma as the presenting fea- polyp with villous adenomatous changes
By analogy with the rest of the large intes- ture {1464}. and focal carcinoma in situ {1243}.
tine, an adenoma-carcinoma sequence is
assumed to occur in the appendix; the Hereditary non-polyposis colorectal can- Genetics
finding of a residual adenoma in some cer (HNPCC) Limited data are available on molecular
cases of adenocarcinoma supports this This familial cancer syndrome confers genetic alterations in appendiceal
contention {1548}. However, some ade- increased susceptibility to proximal tumours, and these data indicate similar-
nocarcinomas appear to arise from gob- colon cancer {1936}, but it is not yet clear ities to those in colorectal tumours. KRAS
let cell carcinoid tumours {209, 250}. whether there is also an increased risk of mutations have been identified in
Compared to adenomas of the colon, appendiceal neoplasms. approximately 70% of appendiceal muci-
adenomas of the appendix are more like- nous adenomas, mostly in codon 12 and
ly to be villous or serrated {250, 706, Other polyposis syndromes a few in codon 13 {1871}. In addition,
1548, 2115, 2110}. It is difficult to establish accurately the KRAS mutation has been identified in an
Many appendiceal serrated and villous risk of genetic susceptibility to tumours of appendix cystadenoma associated with
adenomas display minimal cytological the appendix in Peutz-Jeghers and juve- a long history of ulcerative colitis {1123}.
abnormalities; such lesions need to be nile polyposis syndrome on account of Tumour suppressor gene allelic imbal-
distinguished from hyperplastic polyps or the rarity of these conditions. Intussus- ances have been found in about half of
mucosal hyperplasia. Pedunculated ception with an ‘inside-out’ appendix in appendiceal mucinous adenomas with
hyperplastic polyps of the type seen in Peutz-Jeghers syndrome has been loss of heterozygosity (LOH) at several
the colon are unusual in the appendix, reported, caused by a hamartomatous chromosomal loci, including 5q22, 6q,
but diffuse hyperplasia is relatively com- polyp of the appendix or an appendiceal 17p13, and 18q21. LOH was most fre-
mon {2184}. The diagnosis of hyperplas-
tic polyp/diffuse hyperplasia should not
be made if there are cytological abnor-
malities in the epithelial cells; if any are
present, then the diagnosis of adenoma
should be considered. The presence of
villous structures is also a pointer towards
adenoma.
As they grow, adenomas of the appendix
typically become cystic, and the lining
epithelium becomes undulating rather
than villous. Such lesions may produce a
mucocoele and be given the descriptive
appellation of cystadenoma.

Genetic susceptibility
Familial adenomatous polyposis coli
(FAP)
A review of 71 000 appendix specimens
revealed 33 benign and 6 malignant
appendiceal tumours in patients with
familial polyposis coli {324}. Several
cases of adenocarcinoma of the appen-
dix have been reported in FAP patients,
including a patient with appendiceal Fig. 5.09 Hyperplastic polyp of appendix. Cytological abnormalities of intraepithelial neoplasia are absent.

Adenocarcinoma 97
05 19.7.2006 7:53 Page 98

quent at the 5q locus linked to the APC high-grade, and nonmucinous histology evidence of invasion of underlying struc-
tumour suppressor gene which in the {345, 1365, 1769}. The spread of mucus tures have been found to be poor prog-
colorectum is strongly associated with beyond the right lower quadrant of the nostic factors, whereas complete exci-
transition to adenoma {1871}. In cases of abdomen (whether or not cells are iden- sion of tumour is associated with pro-
pseudomyxoma peritonei (well differenti- tified within it) is an independent prog- longed disease-free survival {346, 1612,
ated mucinous adenocarcinoma), LOH nostic variable, as is the presence of 612}.
at one or two polymorphic microsatellite neoplastic cells outside the visceral peri- Cytological examination of aspirated
loci was seen in approximately half of the toneum of the appendix {250}. When mucus and DNA flow cytometry are
cases and was considered an indication pseudomyxoma peritonei is present, unhelpful in predicting prognosis {612,
of monoclonality. abdominal distension, weight loss, high 707}.
histological grade, and morphological
Prognosis and predictive factors
SEER data showed the 5-year survival Table 5.01
rates for localized adenocarcinoma to be Terminology of epithelial neoplasms of the appendix.
95%, compared with a 5-year survival of
80% for mucinous or cystadenocarcino- Diagnosis Criteria Significance
ma. When distant metastases were pres-
ent, the 5-year survival rates were 0% Adenoma Tumour confined to appendiceal mucosa Does not have the capacitiy to
and 51% respectively {1928}. This (Cystadenoma) and metastasize and can be cured by
No histological evidence of invasion complete local excision.
reflects the low aggressive potential of
mucinous tumours that spread to the Adenocarcinoma Histological evidence of mural invasion Can spread beyond the appendix
peritoneum {1769}. (Cystadenocarcinoma) or with peritoneal, lymph node or dis-
Features that have been associated with Presence of metastases, tant metastases.
a poor prognosis in appendiceal adeno- including spread to peritoneal cavity
carcinoma include advanced stage,

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C. Capella
Endocrine tumours of the appendix E. Solcia
L.H. Sobin
R. Arnold

Definition
Tumours with endocrine differentiation
arising in the appendix.

Epidemiology
Incidence and time trends
Carcinoids account for 50-77% of all
appendiceal neoplasms {1252, 1131}.
Their incidence rate is 0.075 new cases
per 100,000 population per year and
appears to have been decreasing in the
time period 1950-1991 {1251}. Approx-
imately 19% of all carcinoids are located
in the appendix.

Age and sex distribution


The mean age at presentation is 32-43
years (range, 6 to 80 years) {1251, 1252,
1607}. Tubular carcinoids occur at a sig-
nificantly younger age than goblet cell
carcinoids (average, 29 versus 53 years)
{209}.
Appendiceal carcinoids occur more fre- A B
quently in females than in males {1251}. Fig. 5.10 A, B EC-cell carcinoid tumour.
This could reflect the greater number of
incidental appendicectomies performed
in women {1252} but in the SEER data- metastases, usually to the liver and mas of the appendix may be found in any
base, the frequency of non-carcinoid retroperitoneum {1252, 1927}. portion of the appendix and appear as
appendiceal tumours is similar among an area of whitish, sometimes mucoid
males and females, suggesting that the Macroscopy induration without dilatation of the lumen.
higher rate of appendiceal carcinoids in Appendiceal EC-cell carcinoids are firm, They range in size from 0.5 to 2.5 cm
women may not be due solely to higher greyish-white (yellow after fixation), and {442}.
rates of appendicectomy {1251}. fairly well circumscribed, but not encap- Because of their diffusely infiltrative
Furthermore, the prevalence of girls sulated, and measure usually less than nature, goblet cell carcinoids tend not to
among children with appendiceal carci- 1 cm in diameter {1252}. Tumours > 2 cm form distinct tumours and their size gen-
noids can not be explained by differ- are rare; most are located at the tip of the erally cannot be assessed accurately. In
ences in appendicectomy rates {866A, appendix {1254}. Goblet-cell carcinoids a series of 33 cases {209} only two were
1255}. and mixed endocrine-exocrine carcino- suspected grossly; 11 involved the tip
and 22 were circumferential.
Clinical features
The majority of appendiceal endocrine Histopathology
tumours are found incidentally in appen- Carcinoid (well differentiated endocrine
dicectomy specimens; the majority of neoplasm)
these are asymptomatic and located in Most endocrine tumours of the appendix
the distal end of the appendix. In a small are serotonin-producing enterochromaf-
number of cases, carcinoids involving fin (EC)-cell carcinoids, while only a
the remaining portions of the appendix minority are glucagon-like peptide and
may obstruct the lumen and produce PP/PYY-producing L-cell carcinoids and
appendicitis {2059, 209}. mixed endocrine-exocrine carcinomas.
Carcinoid syndrome caused by an They are classifiied according to the
appendiceal carcinoid is extremely rare Fig. 5.11 Carcinoid tumour of appendix with typical WHO histological classification of
and almost always related to widespread yellow colouration. endocrine tumours {1784}.

Endocrine tumours 99
05 19.7.2006 7:53 Page 100

{1115, 586, 1182}. In contrast, sustentac-


ular cells are lacking in ileal and colonic
EC-cell tumours, which develop from EC-
cells of the mucosal crypts {1115, 1291}.

L-cell, glucagon-like peptide


and PP/PYY-producing carcinoid
These are much less common. L-cell
tumours are non-argentaffin, producing
glucagon-like peptides (GLP-1, GLP-2,
Fig. 5.12 Carcinoid tumour infiltrating mesoappendix. and the enteroglucagons glicentin and Fig. 5.13 Small cell carcinoma arising in an appen-
oxyntomodulin) and PP/PYY. They feature diceal tubulovillous adenoma.
a characteristic tubular or trabecular pat-
EC-cell, serotonin-producing carcinoid tern (type B pattern according to Soga
Argentaffin EC-cells, producing both and Tazawa {1775, 820, 1724, 1783}). Brunner glands may be present {2059,
serotonin and substance P, are arranged These tumours generally measure only 2 790}. Mucin stains are intensely positive
in rounded solid nests with some periph- to 3 mm and are the appendiceal coun- within goblet cells and extracellular
eral palisading (type A structure accord- terpart of L-cell tumours that are most fre- mucin pools {790}. Argentaffin and argy-
ing to Soga and Tazawa {1775}). Occa- quent in the rectum. rophil cells, sparse or forming small
sionally, there may also be glandular for- nests, are identified in 50% and 88% of
mations (type C structures), forming a Mixed endocrine-exocrine neoplasms cases, respectively {2059}.
mixed (A+C) pattern. Most tumours dis- This term is used for certain tumours of Immunohistochemically, the endocrine
play muscular and lymphatic invasion or the appendix that show features of both cell component is positive for chromo-
perineural involvement; two thirds of the glandular and endocrine differentiation, granin A, serotonin, enteroglucagon,
cases invade the peritoneum, possibly i.e. goblet cell carcinoid, tubular carci- somatostatin, and/or PP {790, 725}. The
through endolymphatic spread {1252}. noid and mixed carcinoid-adenocarcino- goblet cells express CEA. On ultrastruc-
Despite these signs of apparent aggres- mas {2059, 1254}. tural examination, both dense core
siveness appendiceal carcinoids infre- Goblet-cell carcinoid. This tumour is endocrine granules and mucin droplets
quently produce lymph node or distant characterized by a predominant submu- are found {442, 725}. Both elements are
metastases, in contrast to ileal carci- cosal growth. It typically invades through occasionally present within the cyto-
noids. the appendiceal wall in a concentric plasm of the same cell {442, 790}.
No relevant histologic, cytological, or manner that does not produce a well- Tubular carcinoid. This tumour is often
cytochemical differences have been defined tumour {209}. The mucosa is misinterpreted as a metastatic adenocar-
detected between ileal and appendiceal characteristically spared, with the excep- cinoma, because it does not resemble
carcinoids, despite their very different tion of areas of connection of tumour the typical carcinoid and shows little con-
clinical behaviour, with the exception of nests with the base of the crypts. The tact with the mucosa. It is composed of
the presence of S100-positive sustentac- tumour is composed of small, rounded small, discrete tubules, some with inspis-
ular cells surrounding tumour nests in nests of signet-ring-like cells resembling sated mucin in their lumen. Short trabec-
appendiceal lesions. In this respect, EC- normal intestinal goblet cells, except for ular structures are frequent, but solid
cell appendiceal carcinoids resemble nuclear compression. Lumens are infre- nests are generally absent. In sparse
subepithelial neuroendocrine complexes quently observed. Lysozyme-positive cells or in small groups of tumour cells,
rather than intraepithelial endocrine cells Paneth cells as well as foci resembling the argentaffin reaction is positive in 75%

A B
Fig. 5.14 EC-cell carcinoid tumour. A Chromogranin B. B S-100 immunohistochemistry demonstrating sustentacular cells.

100 Tumours of the appendix


05 19.7.2006 7:53 Page 101

Fig. 5.15 L-cell tumour showing trabecular pattern Fig. 5.16 Clear cell carcinoid. Fig. 5.17 Tubular carcinoid.
and glicentin immunoexpression.

A B C
Fig. 5.18 Goblet cell carcinoid tumour. A Typical concentric mural distribution of tumour with preservation of the appendiceal lumen. Mucin positive tumour nests
(green) are seen in this Movat stain. Lumen is compressed, but intact. B Typical clusters of goblet cells. C Chromogranin A positive cells.

and the argyrophil reaction in 89% of Unlike colonic adenocarcinomas, KRAS Location of tumours at the base of the
cases {2059}. Useful criteria for diagnos- mutations have not been detected either appendix with involvement of the surgi-
ing this tumour are origin from the base in typical or in goblet-cell carcinoid of the cal margin or of the caecum is prognos-
of the crypts, integrity of the luminal appendix {1556}, while in the same tically unfavourable, requiring at least a
mucosa, orderly arrangements, and study, TP53 mutations (mainly G:C to A:T partial caecectomy to avoid residual
absence of cytological abnormalities and transitions) were detected in 25% of gob- tumour or subsequent recurrence {1931}.
mitoses. Immunohistochemically, tumour let-cell carcinoids. The reported frequency of metastases
cells are often positive for chromogranin from appendiceal carcinoids ranged
A, glucagon, serotonin, and IgA, while Prognosis and predictive factors from 1.4% and 8.8% in older series
they are unreactive for S100 protein {586, The majority of patients with endocrine {1252, 1927, 1254, 1780}, while in a more
209}. tumours of the appendix have a recent study the frequency of regional
Mixed carcinoid-adenocarcinoma. This favourable prognosis. Clinically non- metastases was 27%, and that of distant
term has been proposed to designate functioning, non-angioinvasive lesions metastases 8.5% {1251}.
carcinomas of the appendix that arise by confined to the appendiceal wall, and The 5-year survival of patients with
progression from a pre-existing goblet- < 2 cm in diameter are generally cured appendiceal carcinoid is 94% for local-
cell carcinoid. These carcinomas occur by complete local excision, whereas ized disease, 85% for regional disease,
in the apparent absence of neoplastic invasion of the mesoappendix or beyond and 34% for distant metastases {1251}.
change in the mucosal epithelium {209}. or metastatic spread indicates that the Goblet-cell carcinoids are more aggres-
lesion is aggressive. The most important sive than conventional carcinoids, but not
Genetics risk factors appear to be tumour size as malignant as adenocarcinomas of the
Loss of heterozygosity at MEN-1 gene > 2 cm and invasion of the mesoappen- appendix. In one study the percentage of
locus in sporadic appendiceal carci- dix {1134}. Lesions confined to the patients dead of goblet cell carcinoids
noids was reported {829}, but has not appendiceal wall that show angioinva- was 12.5% {442}. Tubular carcinoids, in
been confirmed in more recent studies sion or are > 2 cm in size, carry an uncer- contrast, are clinically benign {209}.
{394, 1938}. tain malignant potential.

Endocrine tumours 101


05 19.7.2006 7:53 Page 102

N.J. Carr
Miscellaneous tumours of the appendix L.H. Sobin
C. Niederau

Neuromas are common in the appendix.


The most frequent manifestation is the
axial neuroma, which causes fibrous
obliteration of the appendiceal lumen.
Occasionally, neuromas may be found in
the mucosa or submucosa without lumi-
nal obliteration {1423, 251, 1818}.
Appendiceal neuromas may be reactive
lesions. Histologically, they consist of a
myxoid and collagenous background
within which a variety of cells is present,
including nerve fibres, spindle cells that
immunoexpress S-100 protein, endo-
crine cells, mast cells and eosinophils. In
this context, the presence of endocrine
cells should not be mistaken for carci-
noid tumour. However, it has been sug-
gested that some carcinoids of the
appendix might develop in the same set-
ting as appendiceal neuroma. {251}. Fig. 5.19 Burkitt lymphoma of appendix.

Stromal tumours may affect the appendix


on rare occasions; they have generally Malignant lymphomas involve the appen- tract, breast, lung, and gallbladder.
been described in the literature as being dix usually as part of more general intes- Metastatic thymoma and melanoma have
of smooth muscle type {324, 865}. tinal spread. Lymphomas presenting as also been reported {130, 98, 570, 607,
primary disease of the appendix are rare; 1051, 1407, 1615, 1822, 2129}. A com-
Kaposi sarcoma may be found in the some are of Burkitt type {1295, 1761}. mon pattern is serosal involvement, pre-
appendix as part of the acquired immuno- sumably due to transcoelomic spread.
deficiency syndrome {406}. Rarely, it Secondary tumours are unusual in the
occurs in individuals without evidence of appendix. Primary sites include carcino-
HIV infection {295}. mas of the gastrointestinal and urogenital

102 Tumours of the appendix