British Division of the
International Academy of Pathology
November 1996
Slide Seminar Histories and Answer Sheet
Edited by
Dr N Rooney
Dr N Shepherd
Table of Contents
History
Female. 45 years. Solitary smooth surfaced 6cms tumour on the antimesenteric aspect of ileum, discovered incidentally at laparoscopic sterilisation. Cut surface solid and pale with haemorrhagic areas.
Microscopy
This is a well demarcated but not encapsulated tumour intermingled with the muscularis propria. The tumour cells are spindle shaped with vascular and epithelioid areas focal myxoid degeneration and pseudoacinar structures. There is focal necrosis and atypical cells. The mitotic rate is 2/30 high power fields. Some pink deposits are present within the tumour which correspond to sphenoid fibres. Immunostaining showed the tumour was positive for vimentin and PGP9.5 but negative with smooth muscle actin and neurone specific enolase, synaptophysin, Leu7, cytokeratin and CD34. Electron microscopy showed dense core granules and sphenoid fibres.
Diagnosis - Gastrointestinal autonomic nerve tumour (GANT).
The tumours are derived from the autonomic nerve plexus and differentiate towards neurones but not schwann cells. They occur in the small bowel stomach and mesentery and may account for many of the epithelioid stromal tumours. As such they are part of the GIST (gastrointestinal stromal tumour group)
References
Gastrointestinal autonomic nerve tumors: A clinicopathological, immunohistochemical, and ultrastructural study of 12 cases. Lauwers GY, Erlandson RA, Casper ES, Brennan MF, Woodruff JM American Journal of Surgical Pathology, 1993 17:887-897
Gastrointestinal autonomic nerve tumours: a report of nine cases. Shanks JH, Harris M, Banerjee SS, Eyden BP. Histopathology 1996 29:111-121
History
Female. 37 years. Long history of small bowel obstruction. Extensive investigations revealed an absence of Raynaud's phenomenon, normal immune status and bone marrow, negative ANAs, normal oesophageal and rectal manometry and normal upper and lower GI endoscopy. Small bowel manometry revealed a total absence of motor activity.
Microscopy
The villi are blunted and there is an increase in inflammatory cells in the lamina propria and epithelium. The muscularis propria is atrophic but there is no fibrosis. There are large numbers of lymphocytes in the submucosa and infiltrating Auerbachs plexus and in areas the lymphocytes can be seen surrounding ganglion cells. These are CD4 positive helper T cells. The diagnosis is of primary inflammatory visceral myopathy. This may occur in association with coeliac disease or systemic sclerosis or may occur denovo as is seen in diffuse lymphocitic inflitrate of the intestine. There was no evidence of coeliac disease or systemic sclerosis in this patient. However while the patient was under observation she developed vascilitic skin lesions and a diagnosis of systemic sclerosis was made.
Diagnosis - Primary Inflammatory Visceral Myopathy
References
Chronic intestinal pseudo-obstruction in two patients. Overlap of features of systemic sclerosis and visceral myopathy Venizelos ID, Shousha S, Bull TB, Parkins RA Histopathology 1988 12 533-540
Intestinal pseudoobstruction caused by diffuse lymphoid infiltration of the small intestine. McDonald GB, Schuffler MD, Kadin ME, Tytgat GNJ. Gastroenterology, 1985 89 882-889
Small intestinal mucosa in pseudo-obstruction syndromes. Schuffler MD, Kaplan LR, Johnson L. Am J Dig Dis 1978 23:821-828
Pathologic observations in systemic sclerosis (scleroderma). D'Angelo WA, Fries JF, Masi AT et al. Am J Med 1969 46: 428-440
History
Female. 49 years. Six-month history of recurring lower abdominal pain. Presented acutely with large bowel obstruction. At laparotomy obstructing tumour of sigmoid colon.
Microscopy
There was evidence of diverticular disease but also of a carcinoma. Adjacent to the carcinoma was an area where benign grandular structures and stroma could be recognised. Both the glands and the stroma were positive for oestrogen receptor confirming the diagnosis of endometriosis. There was no other history of endometriosis in this patient. ER can be helpful in the diagnosis of endometriosis but colorectal cancer in females can be weakly positive in the epithelium but the stroma is always negative.
DIAGNOSIS Endometrioid adenocarcinoma arising in sigmoid colonic endometriosis.
References.
Mucosal changes in the large bowel with endometriosis: A possible cause of misdiagnosis of colitis? Langlois NEI, Park KGM, Keenan RA. Human Pathology, 1994 25 1030-1034
Endometrioid carcinoma arising from endometriosis of the sigmoid colon during estrogenic treatment. Dunn S, Roed-Petersen K, Wilk Michelsen J. Acta Obstet Gynecol Scand 1993 72: 676-678
Diagnosis and management of endometriosis of the colon and rectum. Graham B Mazier WP. Dis Colon Rectum 1988 31: 952-956
The development of malignancy in endometriosis. Scully RE Richardson GS, Barlow JF. Clin Obstet Gynecol 1966 9: 384-388
History
Male. 12 years. Chronic productive cough
Microscopy
The bowel had a grossly thickened wall with extensive sub mucosal and serosal fibrosis. There was focal vascular ectasia and inflammation. The patient had indeed been on high dose pancreatic supplements but only for the five weeks.
DIAGNOSIS Fibrosing colopathy due to pancreatic supplements.
References
Fibrosing colopathy in cystic fibrosis: results of a case controlled study.
Smyth RL etc. Lancet 1995 346 1247-1251
Extensive pathological changes of the colon in cystic fibrosis and high strength pancreatic enzymes.
Knabe N Lancet 1994: 343 1230
Fibrosing colonopathy associated with pancreatic enzymes. Current problems in pharmacovigilance. CSM 1995 21:11
History
Male. 65 years. Acute gut perforation. Longstanding history of malabsorption. Normal peripheral blood count, eosinophil count, albumin and anti-gliadin antibodies. At laparotomy jejunal perforation.
Microscopy
The small bowel adjacent to the ulcer is abnormal with crypt hypertrophy and villous atrophy. There is a marked increase in intra epithelial lymphocytes, all features typical of coeliac disease. The ulcer is infiltrated by a pleomorphic population of large cells with prominent nucleoli. Eosinophils and lymphocytes are admixed with the tumour cells. The tumour cells are positive for CD45, CD45RO, CD3 and CD8 but negative with CD20, CD68 and CAM5.2. The tumour cells are strongly positive with Ki67. Beneath the non ulcerated mucosa is a collection of foamy macrophages. These are probably accumulating lipid in response to lymphatic obstruction by the tumour cells.
DIAGNOSIS Intestinal T-cell lymphoma with/without enterophy.
This is the current terminology in the REAL classification in what was previously called EATL (enteropathy associated T-cell lymphoma).
References
Non-Hodgkin's lymphoma, coeliac disease, and Epstein-Barr virus: A study of 13 cases of enteropathy-associated T- and B-cell lymphoma. Ilyas M, Niedobitek G, Agathanggelou A, Barry RE, Read AE, Tierney R, Young LS, Rooney N Journal of Pathology, 1995, Vol.177, No.2, pp.115-122
Enteropathy-associated T-cell lymphoma in the west of Ireland: Low frequency of Epstein-Barr virus in these tumors. Walsh SV, Egan LJ, Connolly CE, Stevens FM, Egan EL, McCarthy CF Modern Pathology, 1995, Vol.8, No.7, pp.753-757
Schmitt-Graff Intestinal T-cell lymphoma Virchow'Archives 1996 429 27-36
History
Female. 60 years. At time of cholecystectomy, multiple nodules on omentum and mesentery.
Microscopy
This tumour consists of confluent clumps of histiocytoid cells, lymphocytes and some large pink tumour cells. The tumour cells are cytokeratin positive. HMFG1 and 2 postive and weakly positive for S100. The tumour cells were negative for CEA AUAI, LeuM1, CD45 negative. Kappa and Lamda were polyclonal. Electron microscopy showed bushy microvilli on the surface of the tumour cells and intracytoplasmic lumina also with villi.
DIAGNOSIS Lymphohistiocytoid variant of malignant mesothelioma .
References
Lymphohistiocytoid mesothelioma: A rare lymphomatoid variant of predominantly sarcomatoid mesothelioma. Henderson DW, Attwood HD, Constance TJ, Shilkin KB, Steele RH Ultrastructural Pathology, 1988, Vol.12, No.4, pp.367-384
Deciduoid peritoneal mesothelioma: An unusual phenotype affecting young females. Nascimento AG, Keeney GL, Fletcher CDM American Journal of Surgical Pathology, 1994, Vol.18, No.5, pp.439-445
History
Female. 47 years. Diarrhoea and protein-losing enteropathy for 10 weeks. Small bowel resection. The small bowel mucosa was for the most part eroded and covered by a patchy pseudo-membrane. Lesions less marked distally. Sections from the proximal and distal part of the small bowel resection provided.
Microscopy:
Histologically in the section from the proximal part of the small intestine, the intestinal epithelium is totally destroyed and the mucosa is replaced by granulation tissue covered by a thick mucopurulent exudate. There is quite extensive inflammation but this is of a non-specific nature and only patchily extends into the submucosa which is otherwise normal. There is no indication in these sections as to the nature of the aetiological factors involved. In the sections taken from the distal part of the resection however the damage is less severe. The epithelial surface is intact but there is evidence of villous blunting and crypt irregularity associated with a marked inflammatory reaction in the lamina propria. There is no increase in intraepithelial lymphocytes but the enterocytes appear patchily vacuolated. The mucosal infiltrate consists mainly of plasma cells but occasional eosinophils can be detected. The crypts show distinctive changes. First of all there is evidence in places of apoptotic activity; and secondly foci of gastric metaplasia or the ulcer associated cell line can be detected. The overall appearances however are non-specific in character.
It is notable that apoptotic activity is also demonstrated in gastric biopsies and in rectal biopsies taken shortly before intestinal resection was carried out.
Further investigations
Haematology: Initially normal, later became pancytopenic; this soon resolved.
Biochemistry: Bilirubin 49, alkaline phosphatase 455, aspartate aminotransferase 930, alanine aminotransferasc 1545, gamma GT 799. These changes also resolved.
Microbiology: Stools negative for bacteria, parasites, enteroviruses, clostridial toxin. Serology for yersinia, amoebiasis, typhoid, hepatitis viruses, EBV, CMV and parvovirus also negative.
Past History
Prior to the onset of this patient's intestinal disease she had complained of low back pain for two months: she had been given diclofenac sodium, suprofen and lobak. The intestinal appearances taken in conjunction with the aaematological and biochemical investigations would therefore support a diagnosis of severe drug-induced disease.
DIAGNOSIS Acute erosive enteritis (probably drug-related).
References
Park RHR, Mills PR, Russell RI, Lee FD, McArdle C. Acute ulceration of the entire small intestine. Post Grad Med J 1989; 65; 45-48.
Lee FD drug-related pathological lesions of the intestinal tract. Histopathology; 25; 303-308.
History
Male. 46 years. Large mass of `anal warts' present for 20 years. Heterosexual, cigarette smoker. Lesion 20 cms in diameter and encircled the anus. Local excision.
Microscopy
There is a papillomatous lesion with connective tissue cause between the epithiliul cells clefts and a mild lyphpocytid infiltrate. The maturation in the epithilium is uniform with marked koilocytosis. The deep boundary was rounded, well circumscribed and not infiltrative. There was partial keratosis.
Diagnosis giant condyloma of Buschke Loewenstein.
The differential diagnosis of verrucous carcinoma can be excluded by the absence of hyperparakeratosis and keratin filled pits. Furthermore in verrucous carcinoma the connective tissue cause are inconspicuous or absent. Verucous carcinoma is a deeply invasive lesion often associated with sinuses and a dense inflammatory reaction.
References .
Bogomoletz WV, Potet F, Molas G. Condyloma acuminata, giant
condyloma acuminatum (Buschke-Loewenstein tumour) and verrucous carcinoma
of the perianal and anorectal region: a continuous precancerous spectrum?
Histopathology 1985;9:1155-1170.
Pilotti S, D'Amato L, Della-Torre G, Donghi, R, Longoni A, Giarola
M, Sampietro G, De-Palo G, Pierotti MA, Rilke F. Papilloma virus, p53
alteration, and primary carcinoma of the vulva. Diagn Mol Pathol
1995;4:239-48.