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SLIDE SEMINAR CASES 11th Digestive Pathology Course
Bucharest, November 2nd 2018
Alessandro Lugli, MD
Institute of Pathology
University of Bern
Switzerland
61 year old man
Known soor esophagitis
Endoscopically suspicious for eosinophilic esophagitis
Number eos / HPF ?
Biopsies from the middle and distal part of the esophagus
CASE 1 Clinical information
HISTOLOGY Distal esophagus
HISTOLOGY Distal esophagus
HISTOLOGY Middle esophagus
HISTOLOGY Middle esophagus
HISTOLOGY Diagnostic findings
Slight basel cell hyperplasia
Single eosinophils (max. 2 / HPF)
Presence of neutophils and lymphocytes
Special stains (PAS, Grocott): no sign for fungal infection
No dysplasia
HISTOLOGY Diagnosis, but………
Unspecific acute esophagitis
CLINICO-PATHOLOGICAL CONFERENCE Gastroenterology & Pathology
Endoscopically suspicious for an eosinophilic esophagitis
Known HSV infection (Urinary tract)
Reevaluation
HISTOLOGY – DISTAL ESOPHAGUS Peripapillary lymphocytic inflammation
HISTOLOGY – MIDDLE ESOPHAGUS Peripapillary lymphocytic inflammation
MIDDLE ESOPHAGUS IHC: CD3 (57 / HPF)
MIDDLE ESOPHAGUS Immunohistochemistry: additional analysis
Lymphocytes positive additionally for
CD2,CD4, CD7 and CD8
HSV 1 and 2 negative
DIAGNOSIS
Lymphocytic esophagitis
2ND CLINICOPATHOLOGICAL CONFERENCE Gastroenterology & Pathology
Endoscopy: Trachealisation of the esophagus
Antibiotic therapy for urinary tract infection
Therapy with Budenosid
Soor esophagitis suspected
Recovery of the lymphocytic esophagitis ?
HISTOLOGY – DISTAL ESOPHAGIS Soor esophagitis
HISTOLOGY – DISTAL ESOPHAGUS Intraepithelial lymphocytosis
HISTOLOGIE – DISTAL ESOPHAGUS IHC: CD3 (34 / HPF)
FOLLOW UP Clinico-pathological interpretation
Improvement under therapy with Budenosid
Histologically decreased lymphocytic infiltration
Antibiotic therapy for urinary tract infection
Therapy of the soor esophagitis
Clinical and endoscopical follow up
LYMPHOCYTIC ESOPHAGITIS Clinical aspects
More frequent in elderly women
Mean age: 63 years
Dysphagia, odynophagia
Reflux, retrosternal burning
Vomiting, foreign body sensation
Therapy not clear yet (PPI ?)
Haque, Genta, GUT 2012
LYMPHOCYTIC ESOPHAGITIS Endoscopic aspects
Especially peripapillary lymphocytic infiltration
Immunophenotype of T-cells not clear yet
Only few neutrophils and eosinophils
Intercellular edema and spongiosis
Basal cell hyperplasia
LYMPHOCYTIC ESOPHAGITIS Histological aspects
Reflux disease
Infections
Motility disorders
Allergy / Asthma
Autoimmune / dermatologic diseases
Immune suppression (HIV, CVID)
Crohn’s disease (especially in children)
Celiac disease
LYMPHOCYTIC ESOPHAGITIS Etiologic associations
SELECTED LITERATURE
1: Rubio CA, Ichiya T, Schmidt PT. Lymphocytic oesophagitis, eosinophilic oesophagitis and compound
lymphocytic-eosinophilic oesophagitis I: histological and immunohistochemical findings. J Clin Pathol.
2016 Jul 28. pii: jclinpath-2016-203782.
2: Genta RM. Lymphocytic Esophagitis. Gastroenterol Hepatol (N Y). 2015 Aug;11(8):559-61.
3: Xue Y, Suriawinata A, Liu X, Li Z, Gabbard S, Rothstein R, Lacy B, Lisovsky M. Lymphocytic
Esophagitis With CD4 T-cell-predominant Intraepithelial Lymphocytes and Primary Esophageal Motility
Abnormalities: A Potential Novel Clinicopathologic Entity. Am J Surg Pathol. 2015 Nov;39(11):1558-67.
4: Haque S, Genta RM. Lymphocytic oesophagitis: clinicopathological aspects of an emerging
condition. Gut. 2012 Aug;61(8):1108-14.
5: Purdy JK, Appelman HD, Golembeski CP, McKenna BJ. Lymphocytic esophagitis: a chronic or
recurring pattern of esophagitis resembling allergic contact dermatitis. Am J Clin Pathol. 2008
Oct;130(4):508-13.
6: Rubio CA, Sjödahl K, Lagergren J. Lymphocytic esophagitis: a histologic subset of chronic
esophagitis. Am J Clin Pathol. 2006 Mar;125(3):432-7.
52 year old woman
Ulcerative colitis since 2007
Complete remission under therapy with Infliximab since September 2015
Endoscopically mucosal healing, no activity
Chromoendoscopy negative
Ileal polypoid lesion
DD: Adenoma, GIST, NET/NEC
CASE 2 Clinical information
ENDOSCOPY Ileal polypoid lesion (size: 1.5cm)
HISTOLOGY Overview
HISTOLOGY Submucosal spindle cell proliferation
HISTOLOGY Spindle cells not atypic
HISTOLOGY Collagenous stroma
HISTOLOGY No mitoses
HISTOLOGY Scattered blood vessels
HISTOLOGY Immunhistochemistry
S100
SMA
CD34
No expression of c-kit,
DOG1, ALK or Stat6.
Regular expression of
ß-Catenin
HISTOLOGY Diagnosis, but………
Benign mesenchymal proliferation NOS
HISTOLOGY Expression of PDGFα
MOLECULAR PATHOLOGY ANALYSIS PDGFRα Mutation
Molecular Pathology results
Mutation analysis of KIT and PDGFRA:
PCR: KIT exons 9 and 11
Sanger sequencing: KIT Exons 9, 11, 13, 17 and PDGFR exons 12,
14 and 18
KIT mutation analysis: No mutation
PDGFRA mutation analysis:
mutation in exon 18, c.2525A>T (p.D842V)
DIAGNOSIS
Inflammatory fibroid polyp with
degenerative changes
Benign neoplasia (formerly reactive) (Vanek tumor)
Located in the whole GI tract
(Stomach, Small and large intestine, esophagus)
6th – 7th decade; size: 5-20cm
Rare familial cumulation
Clinical symptoms: Abdominal pain, obstruction
Therapy: Endoscopic or surgical excision
Prognosis: Favorable
INFLAMMATORY FIBROID POLYP Clinical aspects
INFLAMMATORY FIBROID POLYP Pathologic aspects
Tumour of the tunica submucosa
May infilitrate the mucosa and/or the muscularis propria (i.e. ileal)
Regular spindled and stellate mesenchymal cells
Onion skin pattern, edema, collagenous stroma, eosinophils, vascular
proliferation
Immunhistochemistry: PDGFRα and CD34 positive
PDGFRα mutation: 50-60% (exon 18 in the stomach, exon 12 in the small
intestine, rarely exon 14)
INFLAMMATORY FIBROID POLYP Differential diagnoses
GIST
- Origin: Muscularis mucosae
- Positiv: CD117, CD34 und DOG1
- KIT and PDGFRα mutation
Inflammatory myofibroblastic tumour
- Origin: Mesenterium
- Cellular myofibroblastic lesion
- ALK positive with ALK gene rearrangements
- Actin, calponin, desmin and caldesmon positive
INFLAMMATORY FIBROID POLYP Differential diagnoses
Leiomyom
- Origin: Submucosa
- Desmin, actin, calponin and
Caldesmon positive
- CD34 and S100 negative
- Hypocellular pattern
Perineuroma
- Origin: Lamina propria
- No inflammation
- EMA, GLUT1 and Claudin-1
positive
- No specific genetic
alterations
Schwannoma
- Origin: Muscularis propria
- Peritumoral, lymphoid
infiltration, few blood vessels
- S100 positive
- No specific genetic alterations
SELECTED LITERATURE
1: Liu TC, Lin MT, Montgomery EA, Singhi AD. Inflammatory fibroid polyps of the gastrointestinal tract:
spectrum of clinical, morphologic, and immunohistochemistry features. Am J Surg Pathol. 2013
Apr;37(4):586-92.
2: Huss S, Wardelmann E, Goltz D, Binot E, Hartmann W, Merkelbach-Bruse S,Büttner R, Schildhaus HU.
Activating PDGFRA mutations in inflammatory fibroid polyps occur in exons 12, 14 and 18 and are
associated with tumour localization. Histopathology. 2012 Jul;61(1):59-68.
3: Daum O, Hatlova J, Mandys V, Grossmann P, Mukensnabl P, Benes Z, Michal M. Comparison of
morphological, immunohistochemical, and molecular genetic features of inflammatory fibroid polyps
(Vanek's tumors). Virchows Arch. 2010 May;456(5):491-7.
4: Ozolek JA, Sasatomi E, Swalsky PA, Rao U, Krasinskas A, Finkelstein SD. Inflammatory fibroid polyps
of the gastrointestinal tract: clinical, pathologic, and molecular characteristics. Appl Immunohistochem Mol
Morphol. 2004 Mar;12(1):59-66.
5: Lasota J, Wang ZF, Sobin LH, Miettinen M. Gain-of-function PDGFRA mutations, earlier reported in
gastrointestinal stromal tumors, are common in small intestinal inflammatory fibroid polyps. A study of 60
cases. Mod Pathol. 2009 Aug;22(8):1049-56.
6: Pantanowitz L, Antonioli DA, Pinkus GS, Shahsafaei A, Odze RD. Inflammatory fibroid polyps of the
gastrointestinal tract: evidence for a dendritic cell origin. Am J Surg Pathol. 2004 Jan;28(1):107-14.
71 year old woman
Screening for colorectal cancer
No gastrointestinal symptoms
Four small polyps in the left colon
Slight diverticulosis
CASE 3 Clinical information
HISTOLOGY Overview
HISTOLOGY Diffuse mast cell infiltration
MC: >100 / HPF
HISTOLOGY Immunohistochemistry: c-kit expression
HISTOLOGY Immunohistochemistry: mast cell tryptase expression
HISTOLOGY Immunohistochemistry: CD25 expression
HISTOLOGIC AND MOLECULAR DIAGNOSIS
Systemic mastocytosis
KIT p.D816V mutation
SYSTEMIC MASTOCYTOSIS Clinical aspects
GI Trakt involved in approximately 70%
Skin lesions may be absent in 50% of cases; abdominal pain and diarrhoea
Clinical variants:
Indolent systemic mastocytosis
Systemic mastocytosis with associated clonal hematologic
Non-mast cell linear disease
Aggressive systemic mastocytosis
Mast cell leukemia
Diagnosis is based on one major and one minor or three minor criteria
Therapy:
Indolent variant: H1 and H2 histamine anatgonists
Severe variant: Interferon-α-2b, Imatinib, corticosteroids
Prognosis: No curative therapy available; variant dependent
Macroscopy
Erythema, teleangiectasis, nodular lesions or multiple polyps
Histology
Subepithelial linear mast cell infiltration
Nodular and polypoid lesions: diffuse and confluent mast cell infiltration
Cytologically spindle-like and round nuclei with clear cytoplasm
Co-expression of C-kit and CD25 in mast cells is diagnostic
for a systemic mastocytosis
KITD816V mutation
SYSTEMIC MASTOCYTOSIS Pathologic aspects
Major criteria
Multifocal dense mast cell infiltration within the tissue (≥15 cells)
Minor criteria
>25% spindle cel-like, immature or atypic mast cells
KITD816V mutation
CD25 and/or CD2 expression in mast cells
Serum tryptase continuously increased (>20 ng/mL) in absence of a
clonal myleoid disease
Diagnosis is based on one major and one minor or three minor criteria !
SYSTEMIC MASTOCYTOSIS Diagnosic criteria
Mastocytic enterocolitis
Not associated with systemic mastocytosis
Increased mast cell number (>20 / HPF) as in chronic diarrhoea
Mantle cell lymphoma
Expression of CD20, CD5 and cyclin D1
MALT lymphoma
Lympho-epithelial lesions and CD20 expression
Inflammatory bowel disease (IBD)
Crypt distorsion
Cryptitis and crypt abscess
Basal plasmocytosise
SYSTEMIC MASTOCYTOSIS Differential diagnoses
SELECTED LITERATURE
1: Doyle LA, Sepehr GJ, Hamilton MJ, Akin C, Castells MC, Hornick JL. A clinicopathologic study
of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessment of
mucosal mast cell density in irritable bowel syndrome and asymptomatic patients. Am J Surg
Pathol. 2014 Jun;38(6):832-43.
2: Chiu A, Orazi A. Mastocytosis and related disorders. Semin Diagn Pathol. 2012 Feb;29(1):19-
30. Review.
3: Hollmann TJ, Brenn T, Hornick JL. CD25 expression on cutaneous mast cells from adult
patients presenting with urticaria pigmentosa is predictive of systemic mastocytosis. Am J Surg
Pathol. 2008 Jan;32(1):139-45.
4: Hahn HP, Hornick JL. Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is
specific for systemic mastocytosis. Am J Surg Pathol. 2007 Nov;31(11):1669-76.
5: Jakate S, Demeo M, John R, Tobin M, Keshavarzian A. Mastocytic enterocolitis: increased
mucosal mast cells in chronic intractable diarrhea. Arch Pathol Lab Med. 2006 Mar;130(3):362-7.
6: Siegert SI, Diebold J, Ludolph-Hauser D, Löhrs U. Are gastrointestinal mucosal mast cells
increased in patients with systemic mastocytosis? Am J Clin Pathol. 2004 Oct;122(4):560-5.
THANK YOU FOR YOUR ATTENTION !