CS05 NEW DEVELOPMENTS IN GASTROINTESTINAL PATHOLOGY-GIPS FUNNY FORMS OF ESOPHAGITIS: BEYOND GERD AND EOSINOPHILIC ESOPHAGITIS

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CS05 NEW DEVELOPMENTS IN GASTROINTESTINAL PATHOLOGY-GIPS FUNNY FORMS OF ESOPHAGITIS: BEYOND GERD AND EOSINOPHILIC ESOPHAGITIS Rhonda K. Yantiss, M.D. Professor of Pathology and Laboratory Medicine Weill Cornell Medicine New York, NY

IN THE PAST 12 MONTHS, I HAVE NOT HAD A SIGNIFICANT FINANCIAL INTEREST OR OTHER RELATIONSHIP WITH THE MANUFACTURER(S) OF THE PRODUCT(S) OR PROVIDER(S) OF THE SERVICE(S) THAT WILL BE DISCUSSED IN MY PRESENTATION.

CASE 1 30-year old woman with dysphagia History of psoriasis

Patchy parakeratosis Epithelial hyperplasia

Lots of intraepithelial lymphocytes

OUTCOME Case shown to dermatopathology Psoriasis of the esophagus The esophagus is lined by squamous epithelium, but it isn t the skin Patterns of cutaneous inflammation generally don t mean the same thing in the esophagus

LYMPHOCYTIC ESOPHAGITIS Increasingly recognized as more patients undergo biopsy of proximal esophagus for eosinophilic esophagitis 80% of cases identified in past 5 years Females affected more than males, older adults Manifestation of Crohn disease in children May be associated with other immune-mediated disorders Dysphagia, odynophagia, dysmotility Endoscopy 30% normal Plaques, rings, furrows simulating eosinophilic esophagitis Histology 20-100 lymphocytes/high-power field Granulocytes should be infrequent, or absent

Lymphocy5c esophagi5s Lymphocytes most numerous in peripapillary epithelium

Lymphocy5c esophagi5s Mucosal injury with edema and cellular necrosis

Clustered in epithelium Dyskerato5c cells Lymphocy5c esophagi5s

How about this one? 60- year old female with dyspepsia

Lymphocytes in GERD, ogen 20/HPF or more

Candidal esophagi5s

Neutrophils are a clue to Candida

THERE ARE MANY CAUSES OF ESOPHAGEAL LYMPHOCYTOSIS.A DIAGNOSIS OF LYMPHOCYTIC ESOPHAGITIS REQUIRES CLINICAL CORRELATION

LYMPHOCYTIC ESOPHAGITIS DIAGNOSTIC CRITERIA I generally don t make this diagnosis unless There are numerous intraepithelial lymphocytes with clustering and evidence of injury Dyskeratotic epithelial cells Intercellular edema Other etiologies (GERD, eosinophilic esophagitis, candidiasis, stasis) rigorously excluded Endoscopic findings suggest a diffuse mucosal abnormality (not just near the GE junction) Restricted definition likely identifies a group of patients with immune-mediated or drug-related injury similar to lymphocytic itis of the remaining GI tract

CASE 82-year old woman with CHF, COPD, recent fall Admitted to evaluate iron deficiency anemia

ESOPHAGITIS DISSECANS SUPERFICIALIS SLOUGHING ESOPHAGITIS Elderly patients Men and women equally affected Asymptomatic, dysphagia Self-limited with endoscopic resolution Chronic debilitating diseases Medications NSAIDs, bisphosphonates, potassium chloride CNS depressants Medications that cause dry mouth (opioids, SSRIs)

Desquama5on Underlying mucosa essen5ally normal

Two- toned layer of parakeratosis

Normal squamous epithelium

Necro5c parakeratosis

How about this one? Underlying mucosa is not normal 72- year old female with odynophagia

Thin strips of parakerato5c material; not dead or two- toned

Thin mucosa Radia5on injury Vacuolated weird cells in basal zone

GraG versus Host Disease

GraG versus Host Disease Apopto5c kera5nocytes Degenerated basal kera5nocytes

Pemphigus vulgaris; esophageal desquama5on, but subtle histologic findings

Bullae are flaccid, so may be disrupted or desquama5ve; confirm with DIF for intercellular IgG and C3 deposits Tombstone appearance of clinging basal kera5nocytes

Alendronate: severe injury, may completely desquamate

Alendronate: extensive necrosis

THERE ARE MANY MIMICS OF SLOUGHING ESOPHAGITIS.THE HISTOLOGIC DIAGNOSIS REQUIRES CLINICOPATHOLOGIC CORRELATION

ESOPHAGITIS DISSECANS SUPERFICIALIS DIAGNOSTIC CRITERIA I generally don t make this diagnosis unless There is two-toned parakeratosis with necrosis of superficial layer The epithelium under parakeratosis is normal The clinical picture fits Endoscopy shows diffuse desquamation with normal underlying mucosa Other etiologies are excluded Radiation Graft versus host disease Bullous disorders Drugs (bisphosphonates)

CASE 30-year old woman with odynophagia Otherwise well

Pa5ent was receiving doxycycline for acne treatment

PILL ESOPHAGITIS More common among older patients Sites of luminal narrowing (GE junction, extrinsic compression) Many medications can cause injury, but the big offenders are Tetracyclines (treatment of acne) Tetracycline, doxycycline, minocycline, oxytetracycline Bisphosphonates (alendronate) Iron Kayexelate

Ulcer debris may contain foreign material (pill fragments)

Pill fragments in epithelium

Refrac5le material is not specific; common component of enteric coa5ng

Tetracyclines: striking mucosal edema or bullae with neutrophils

Tetracyclines: striking mucosal edema or bullae with neutrophils

Alendronate: extensive necrosis

Iron pill esophagi5s

Kayexelate

Kayexelate

Fish scales Purple, jagged Kayexelate Pink with yellow edge two- toned Cracked scales Sevelamer Bright red, purple No internal structure None of these Cholestyramine

MEDICATION-RELATED ESOPHAGEAL INJURY Consider a drug injury when Foreign material is embedded in inflammatory foci (recognize kayexelate and iron) Mucosal necrosis Bottom heavy pattern of injury with edema and inflammation (neutrophils) Disease is discontinuous with gastroesophageal junction Ulcers in mid/upper esophagus

LESS COMMON CAUSES OF ESOPHAGITIS TAKE HOME POINTS Diverse types of injury can produce similar histologic changes Clues to classification Distribution of injury in mucosa Nature of inflammatory infiltrate Severity of epithelial injury Correlation with clinical history, medication list, and endoscopy The best ancillary test is often a phone call