COVID-19 Update - This is to inform you that the Government of India has announced a complete lockdown in India 22nd March 2020 to 3rd May 2020. As a result, our offices will now be closed till 3rd May 2020 and all our employees will be working from home. Office telephones will not be answered, and therefore you are requested to direct all your queries related to manuscript submission, review process, publication etc. at below mentioned details. editor@innovativepublication.com, rakesh.its@gmail.com, Mob. 8826373757, 8826859373, 9910947804


Print ISSN:-2581-5725

Online ISSN:-2456-9267

CODEN : IACHCL

Current Issue

Year 2020

Volume: 5 , Issue: 1

  • Article highlights
  • Article tables
  • Article images

Article Access statistics

Viewed: 60

Emailed: 0

PDF Downloaded: 42

Ch. Geetha, Farheen, and Deshpande: Histopathologic study of Mucinous lesions of the appendix


Introduction

Mucinous lesions of appendix are rare and account for 0 .2 – 0.7% of all appendicetomy surgeries.5, 4, 3, 2, 1 T hey are complex, diverse group of epithelial neoplasms ranging from simple mucoceles to complex pseudomyxoma peritonei. In 1842, Rokitansky first described mucocele as a dilatation of the appendiceal lumen by an abnormal mucus accumulation.6 Morphologically mucocele refers to cystic dilatation of appendix due to accumulation of gelationous material.

Mucoceles of appendix are divided into four types based on histology: (1) simple retention cysts, (2) mucosal hyperplasia, (3) mucinous adenoma, and (4) mucinous adenocarcinoma.1 The clinical presentation is nonspecific abdominal pain and sometimes as acute appendicitis because of localised inflammation. Mostly clinical presentation is rather non-specific making preoperative diagnosis rare. Histopathology is very crucial for diagnosis and categorisation of mucinous lesions.

In this study, we evaulated clinical, radiological and histopathological findings of all the mucinous lesions of appendix.

Materials and Methods

It is a retrospective study carried out at KAMSRC from 2013 to 2017 over a period of five years. It included ten cases of mucinous lesions of appendix. Clinical details and radiological findings were retrieved from case sheets.

All the specimens are collected in 10% neutral buffered formalin (NBF). Gross examination findings are noted in all the cases and the sections are taken accordingly. Sections are stained with Hematoxylin & Eosin (H&E). Special stain for mucin was done with AB-PAS as and when required. Diagnosis and classification is based on WHO 20107 and recommendations in the AJCC 8th edition.8

Results

Mucinous lesions of appendix are rare and accounted for 0.8% of all the appendicetomy specimends. Benign lesions include simple mucoceles or retention cysts and benign neoplastic adenomas. Malignant lesions include invasive adenocarcinomas.

Benign lesions are more common than malignant lesions and account for 50% of all lesions. All the benign lesions are seen in females at a younger age in contrast to malignant lesions which are seen in males at an older age.

All the patients presented with clinical features of appendicitis (4 cases), pain abdomen (4 cases), abdominal pain and mass (2 cases)

Simple Mucocele (Retention cyst) are seen in 2/10 cases. One case was seen in 26 years female who presented with chronic appendicitis and underwent interval appendicectomy. Other case is seen in 35 years female with dilated appendix. Gross examination revealed dilated appendix filled with mucoid material. Histopathology showed dilated lumen filled with mucinous material, lined by single layered, flattened epithelium. There is no proliferation or atypia of the lining epithelium.

The 2010 WHO classification recognizes 3 main categories of mucinous neoplasms: mucinous adenoma, LAMN and appendiceal adenocarcinoma.7

Benign mucinous adenomas accounted for 33% (3/10) cases (Figure 1). All the cases are seen in females with mean age of 44 year. Two cases clinically presented as appendicitis and one case presented with abdominal pain. Imaging revealed dilated appendix in two cases. One case was diagnosed as mucocele on ultrasonography. Gross examination revealed dilated appendix filled with mucin. Microscopy shows appendiceal mucosa thrown into villous architecture, composed of benign columnar cells with stratification and abundant mucin and is confined to mucosa with no evidence of invasion beyond muscularis mucosa.

Low grade appendiceal mucinous neoplasm (LAMN); One case 1/10 of LAMN is seen in our study. It is seen in 36 years female who presented with abdominal pain and mass and ultrasound revealed dilated appendix. Gross examination revealed dilated appendix of 6x7cm. filled with mucin. Histopathology revealed w ell differentiated adenoma with acellular mucin dissecting the musclaris propria of appendix. There is flattened epithelial growth with loss of muscularis mucosae and mild fibrosis of submucosa.In our study, LAMN is associated with low grade pseudomyxoma peritonei (PMP) with pools of mucin and scaterred epithelial cells showing low grade cytological atpia in seperately received omental biopsy

Mucinous cystadenocarcinoma is seen in 4 cases accounting for 40 % cases (Figure 2). All are males with a mean age of 60 yrs. Abdominal pain is the most common symptom. Imaging findings showed perforated appendix in two case s and growth at the base of the appendix in other case, Grossly the appendix is markedly enlarged with serosal congestion in all cases and two cases revealed perforation. Microscopy is characterised by invasive neoplastic glands with high grade cellular atypia and nuclear pleomorphism and mitotic activity extending into muscularis propria.

Mucinous hyperplasia and High grade appendiceal mucinous neoplasm(HAMN) are not encountered in our study

Summary of all the cases:

Table 1
S. No Age Gender Clinical Diagnosis Radiology findings Histopathology
1 32 F Abdominal pain-Appendicitis Dilated appendix Benign Mucinous Adenoma
2 50 F Abdominal pain Dilated appendix Benign Mucinous Adenoma
3 36 F Abdominal pain and mass Dilated appendix LAMN w ith pseudomyxoma peritonei
4 46 M Abdominal pain and mass USG;Dilated appendix CT-growth at the base of appendix Mucinous Adenocarcinoma
5 60 M Abdominal pain Dilated appendix Mucinous Adenocarcinoma
6 60 M Abdominal pain Perforated appendix Mucinous Adenocarcinoma
7 61 M Appendicitis Perforated appendix Mucinous Adenocarcinoma
8 26 F Appendicitis Interval appendicectomy Retention cyst (Simple mucocele)
9 50 F Appendicitis Dilated appendix Benign Mucinous Adenoma
10 48 F Pain abdomen Dilated appendix Retention cyst (Simple mucocele)
Figure 1

Mucinous adenoma(A )Dilated appendix ith dilated lumen obliterated by mucinous material (B) Appendiceal mucosa is lined by papillary folds composed of benign columnar cells with stratification and abundant mucin (H&E 200x)

https://s3-us-west-2.amazonaws.com/typeset-media-server/61aacd60-2f1d-47ee-8c68-4bde76f8fb3eimage1.png

Figure 2

Mucinous adenocarcinoma (A)Dilated appendix with mucinous material at the base (B) Appendiceal mucosa is lined by papillary neoplastic glands infiltrating muscularis (H&E 200x)

https://s3-us-west-2.amazonaws.com/typeset-media-server/61aacd60-2f1d-47ee-8c68-4bde76f8fb3eimage2.png

Discussion;

Primary tumors of the appendix are rare and represent less than 2% of surgical appendectomy specimens9 They include epithelial tumors, carcinoid tumors, mesenchymal tumors, lymphomas. Mucinous neoplasms of the appendix are still rare and second only to carcinoids10

Mucocele of the appendix can result from obstruction of appendiceal ostium due to mucus, mucuous hyperplasia, benign and malignant lesions. Other causes include fecal impaction or polyps of the cecum, inflammation from surrounding tissues1 and rare causes found in the literature are endometriosis and metastatic melanoma.12, 11 Presently the term mucocele is only used for the macroscopic description or for imaging and as a clinical term, never as a definitive diagnosis

Mucoceles of appendix are divided into four types based on histology: (1) simple retention cysts, (2) mucosal hyperplasia, (3) mucinous cystadenoma, and (4) mucinous cystadenocarcinoma.1

Simple mucoceles are retention cysts, characterised by accumulation of mucus with normal epithelial lining and rarely exceed 2 cm.14, 13 They result from an obstructing fecolith, extrinsic compression or inflammatory conditions and rarely endometriosis.

Mucinous neoplasms of appendix include Mucinous adenoma, Low-grade appendiceal mucinous neoplasm and Mucinous adenocarcinoma. Salient features of these three entities is summarised in Table 2

There are no cases of Mucinous hyperplasia and High grade appendiceal mucinous neoplasm in our study.

Table 2
Mucinous adenoma Low-grade appendiceal mucinous neoplasm (LAMN) Mucinous adenocarcinoma
Confined to appendiceal mucosa Non-invasive glands with mucin dissecting beyond the appendix Invasive glands extending beyond the appendix
No extra-appendiceal mucin Acellular or cellular extra- appendiceal mucin Invasive epithelium in the extra-appendiceal mucin
Not associated with PMP Associated with low-grade PMP Associated with high-grade PMP
PMP Benign, no recurrences Frequent recurrences ˂10% 10-year survival

Salient features of mucinous appendiceal neoplasms17, 16, 15, 14, 13, 7

Table 3
Parameter Cerame MA 19 Nitecki SS 18 Present Study
Age 57.1 56.5 60
M:F 1.4:1 1.2:1 All are males
Presentation as Acute appendicitis 68% 50% 50%
Perforation 50% - 50%

Mucinous adenocarc inoma

Mucinous lesions of appendix are rare and accounted for 0.8% (10/1200) of all the appendicectomy specimens in our study. This is in comparision to other studies where they represented 0.2 – 0.7% of all appendicetomy surgeries5, 4, 3, 2, 1

Benign mucinous lesions are more common than malignant lesions similar to studies by Morano et al and Higa et al20, 1

In our study, Male to female ratio is 2:3. This is in contrast to other studies by Carr NJ et al.16 which showed a male predominance (5 : 2). But in comparision to a retrospective study of 135 patients by Omari et al.10 where 55% were females

Benign and mucinous lesions as a whole are more common in females as comparable to study by Morano WF.20 Higa et al1

Mucoceles and mucinous cystadenomas are seen in females and all the mucinous adeno carcinomas are seen in males. However, AM are considered to occur more frequently in women.21 Mucinous cystadenomas have high frequency in women compared to men with a ratio of 4:1, and it tends to affect patients over 50 years of age.6 Other tumors of the gastro intestinal tract, ovary, breast and kidney can be associated in up to one-third of the patients.21 Omari et al. recommend surveillance colonoscopy in patients with diagnosis of neoplastic mucinous lesions of appendix.21

All the cases of adeno cacinoma are seen in males and in the sixth decade similar to study to Tirumani et al.17 They have an increased association with other colonic neoplasia and chronic ulcerative colitis but such association is not seen in our study.

Mean age of presentation of mucinous cystadenoma is 44 years, mucinous cystadeno carcinoma is 56.7 years. Cystadenocarcinomas are seen at a later age than cystadenomas similar to other studies

The most common clinical presentation is nonspecific abdominal pain as seen in 60% of cases similar to study by Emre et al.22 Abdominal pain is associated with mass in two cases. Appendicitis as clinical presentation is seen in 40% of all the cases in contrast to other studies by Omari et al21 where only 8% to 14% of the cases presented as acute appendicitis.21, 3 Ruiz-Tovar et al.3 reported 14% of their patients had an intraoperative diagnosis of appendicitis with AM. Other features can be weight loss, nausea and vomiting, obstipation, and change in bowel habits. They can also present as intestinal strangulation, appendiceal intussusception, or generalised abdominal pain5

Mostly clinical presentation is rather non-specific making preoperative diagnosis difficult. Preo perative diagnosis is possible with the help of radiological investigations (abdominal USG, CT, or MRI) when there is cystic dilation of the appendix, mural calcification of the appendix wall, luminal diameter greater than 15mm. Macroscopic appearance of the appendix examined intraoperatively gives a clue to the diagnosis. Histopathological examination of the specimen.25, 24, 23 enables the establishment of final diagnosis. In our study, USG was done in all the cases which revealed a dilated appendix. CT scan was done in one case of adeno carcinoma which showed growth at the base of appendix.

Simple retention cyst of appendix is non-neoplastic dilated appendix filled with mucin. There are two cases in our study.

Histopathology showed flattened lining epithelium with no atypia. Most of the benign mucoceles are asymptomatic. These are mostly detected incidentally during ultrasonography, computed tomography and other radiographic examinations of gastrointestinal tract, or during a laparotomy.5 Simple appendectomy is the treatment of choice for simple mucoceles.

Mucinous adenomas

Adenomas show female predominance and typically occur in fifth decade but the age range is wide.1Abdominal pain that mimics acute appendicitis is the most common clinical presentation.1 It can also present as an abdominal mass or as intussusception of the appendix or can be asymptomatic.

Grossly, appendix is dilated and filled with mucin. The serosa is smooth with absent mucin.

Microscopic examination reveals tumors limited to mucosa with intact muscularis mucosae. There is no mucin dissecting into the wall or mucin extrusion outside the appendix. The tumor consists of a proliferation of mucinous epithelial cells thrown into villi.

Appendiceal adenomas are benign and are treated by appendectomy alone.

LAMN with pseudomyxoma peritoni

Low-grade appendiceal mucinous neoplasm (LAMN) is a rare malignancy accounting for 1% of gastrointestinal neoplasms and is found in less than 0.3% of appendectomy specimens.27, 26 In our study only one case is seen accounting to 0.1% of all appendicetomy specimens.

They are commonly seen in men, particularly in the sixth decade in contrast in our study where LAMN is seen in 36 years female w ho presented with abdominal pain and mass. Other symptoms include abdominal pain, intussusception, and obstruction and some times asymptomatic.

Complications of LAMN include intussusception, ureteral obstruction, volvulus, small bowel obstruction (SBO), rupture, and PMP27, 26 In our case, it is associated with low grade PMP. PMP refers to the accumulation of mucin within the peritoneal cavity secondary to mucinous epithelial neoplasia. This most often occurs because of peritoneal spread of a mucinous neoplasm from the appendix but has been described with mucinous tumors from other sites, including colon, ovary, gallbladder, pancreas, and urachus.

Imaging modalities for diagnosis include ultrasound (USG) and CT. In our case, USG w as done which showed dilated appendix and CT scan revealed PMP.

Grossly, LAMN shows markedly dilated appendix filled with mucin. There is hyalinization and fibrosis of the appendiceal wall.28, 27, 26 LAMNs less than two centimeters (cm) are rarely malignant. Masses larger than 6 cm have higher risk of malignant cells, a higher risk of appendiceal perforation, and development of PMP.27

Histopathology shows low grade atypical glandular cells and epithelial cells with “ pushing invasion ” of atypical cells creeping into the appendiceal wall with possible diverticular formation.28 In our case, histopathology showed mucin pools and strips of cells on the serosal surface

Management of LAMN includes the prevention of rupture, seeding, and development of PMP.27 Right hemicolectomy with or without omentectomy is recommended when there is infiltration of malignancy into submucosa or with the presence of lymph node metastasis.29

Mucinous adeno carcinoma

Adenocarcinomas of the appendix are rare entities, representing <0.5% of all gastrointestinal malignancies and 4-6% over lesions of the appendix neoplasm 9. Collins et al30 found an incidence of 0.082% among 50 000 appendectomy specimens. There is an increased incidence among men in some series8,18 but not in others.19, 31 Patients usually present in fifth to seventh decade of life31, 18 and us ually as acute appendicitis. Other less common modes of presentation include a palpable mass, obstruction, gastrointestinal bleeding, or symptoms.

Appendiceal adenocarcinomas are classified as adenocarcinoma not otherwise specified, mucinous adenocarcinoma, signet ring cell adenocarcinoma, and undifferentiated carcinoma. Only Mucinous adenocarcinoma are included in our study.

Invasive adenoca rcinoma of the appendix is surgically treated by right hemicolectomy and lymph node dissection, in order to stage the tumor and ensure complete resection.19

In our study all the cases are diagnosed on histopathology of appendicetomy specimens. Right hemicolectomy was advised in all the cases. Further follow-up details are not available.

Comparitive study of age, M :F ratio, clinical presentation of mucinous adeno carcinoma with other studies is summarised in Table 3.

Conclusion

Mucinous lesions of appendix are rare. Mucinous lesions range from simple mucocele to mucinous adenocarcinomas. They are more common in females. Most of them present with non-specific abdominal pain making pre-operative clinical diagnosis difficult. Imaging shows dilated appendix. Intra operative gross examination gives us a clue to diagnosis. Final diagnosis is established by histopathological study of the excised specimen. Neoplasms confined to the mucosa of the appendix are adenomas, whereas neoplasms extending beyond the appendix can be LAMNs or adenocarcinomas. The treatment for simple mucocele is appendectomy. Right hemicolectomy is advised for intermediate /malignant lesions depending on the size and location. Maximum care should be taken to avoid intraperi­ toneal rupture of a mucocele because of the risk of PMP. Risk of developing adenocarcinoma in colon, ovary, endometrium, breast, kidney is greater in patients with a mucocele than in the general population, warranting regular cancer survillence and monitoring in these cases. Clear communication between the radiologist, pathologist and surgeon is essential for optimal patient management.

Source of funding

None.

Conflict of interest

None.

References

1 

E J Rosai C A Pizzimbono L Wise Mucosal hyperplasia, mucinous cystadenoma, and mucinous cystadenocarcinoma of the appendix. A re-evaluation of appendiceal‘mucoceleCancer197332615251541

2 

Ravi Marudanayagam Geraint T Williams Brian I Rees Review of the pathological results of 2660 appendicectomy specimensJ Gastroenterol2006418745749

3 

J. Ruiz-Tovar D. García Teruel V. Morales Castiñeiras A. Sanjuanbenito Dehesa P. López Quindós E. Martínez Molina Mucocele of the AppendixWorld J Surg2007313542548

4 

R.M. Smeenk M.L.F. van Velthuysen V.J. Verwaal F.A.N. Zoetmulder Appendiceal neoplasms and pseudomyxoma peritonei: A population based studyEur J Surg Oncol (EJSO)2008342196201

5 

S Yakan C Caliskan A Uguz M A Korkut A C¸oker A retrospective study on mucocele of the appendix presented with acute abdomen or acute appendicitisHong Kong J Emerg Med2011183144149

6 

C Rokitansky A Manual of Pathological AnatomyA Manual of Pathological Anatomy21855

7 

N Carr L Sobin F Carneiro F T Bosman F Carneiro R H Hruban N D Theise Tumors of the appendixWorld Health Organization classification of tumours 4th edn.Lyon, France: IARC Press2010122125

8 

N J Carr T D Cecil F Mohamed Peritoneal Surface Oncology Group International. A consensus for classification and pathologic reporting of pseudomyxoma peritonei and associated appendiceal neoplasia: the results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi ProcessAm J Surg Pathol20164011426

9 

S J Connor G B Hanna F A Frizelle Appendiceal tumors: retrospective clinicopathologic analysis of appendiceal tumors from 7,970 appendectomiesDis Colon Rectum1998417580

10 

Perry J. Pickhardt Angela D. Levy Charles A. Rohrmann Amir I. Kende Primary Neoplasms of the Appendix: Radiologic Spectrum of Disease with Pathologic CorrelationRadio Graphics2003233645662

11 

A A Alduaij M B Resnick M Kawata V E Pricolo Metastatic malignant melanoma presenting as an appendicealJ Oncol201120114

12 

D K Driman D E Melega G A Vilos E A Plewes Mucocele of the appendix secondary to endometriosis: report Case Reports in Oncological Medicine 5 of two cases, one with localized pseudomyxoma peritonei,Am J Clin Pathol20001136860864

13 

R K Pai T A Longacre Appendiceal mucinous tumors and pseudomyxoma peritonei: histologic features, diagnostic problems, and proposed classificationAdv Anat Pathol 200512291311

14 

R K Pai A H Beck J A Norton T A Longacre Appendiceal mucinousneoplasms: clinicopathologic study of 116 cases with analysis of factors predicting recurrenceAm J Surg Pathol 20093314251439

15 

J Misdraji Appendiceal mucinous neoplasms: controversialissuesArch Pathol Lab Med2010134864870

16 

N J Carr W F Mccarthy L H Sobin Epithelial noncarcinoid tumors and tumor-like lesions of the appendix. A clinicopathologic study of 184 patients with a multivariate analysis of prognostic factorsCancer199575757768

17 

S H Tirumania M F Hill R Auer Mucinous neoplasms of the appendix: a current comprehensive clinicopathologic and imaging reviewCancer Imaging20131311425

18 

Samy S. Nitecki Bruce G. Wolff Richard Schlinkert Michael G. Sarr The Natural History of Surgically Treated Primary Adenocarcinoma of the AppendixAnn Surg199421915157

19 

M A Cerame A 25-year review of adenocarcinoma ofthe appendix. A frequently perforating carcinomaDis Colon Rectum198831145150

20 

F Morano Gleeson Clinicopathological features and management of appendiceal mucoceles;a systamic reviewAm surg2018842273281

21 

Abdelkarim H Omari Muhammad R Khammash Ghazi R Qasaimeh Ahmad K Shammari Mohammad K Bani Yaseen Sahel K Hammori Acute appendicitis in the elderly: risk factors for perforationWorld J Emerg Surg201491

22 

A Emre M Sertkaya I Taner Kale Clinicopathological analysis of appendiceal mucinous tumors: A single-center experienceTurk J Surg 201733274278

23 

Murat Ozgur Kilic Aydin Inan Mikdat Bozer Four mucinous cystadenoma of the appendix treated by different approachesTurk J Surg20143029799

24 

F U Malya M Hasbahceci A Serter G Cipe O Karatepe E Kocakoc Appendiceal mucocele: clinical and imaging features of 14casesChirurgia (Bucur)2014109788793

25 

L Stocchi B G Wolff D R Larson J R Harrington Surgical Treatment ofAppendiceal MucoceleArch Surg2003138585590

26 

V Ramaswamy Pathology of mucinous appendiceal tumors and pseudomyxoma peritoneiIndian J Surg Oncol20167258267

27 

Vennila Padmanaban William F. Morano Elizabeth Gleeson Anshu Aggarwal Beth L. Mapow David E. Stein Incidentally discovered low-grade appendiceal mucinous neoplasm: a precursor to pseudomyxoma peritoneiClin Case Rep2016411121116

28 

Joseph Misdraji Robert H. Young Primary epithelial neoplasms and other epithelial lesions of the appendix (excluding carcinoid tumors)Seminars Diagn Pathol2004212120133

29 

K J Kelly Management of appendix cancerClin Colon Rectal Surg201528247255

30 

D C Collins Adenomatous polyps of the vermiform appendixSurg Clin North Am19321210631067

31 

G M Proulx C G Willett Daleyw Appendiceal carcinoma:patterns of failure following surgery and implications for adjuvant therapyJ Surg Oncol 1997665153



jats-html.xsl

© 2020 Published by Innovative Publication. This is an open access article under the CC BY-NC license (creativecommons.org)