The 11th International Course on the Pathology of the Digestive System CASE 2 Alina Nicolae MD, PhD
Clinical History 20-year-old female patient Jan 2016 - acute right lower quadrant abdominal pain, nausea, vomiting, fever Ultrasonography enlargement of the appendix, no other lesions Laparotomy - appendectomy has been performed Macroscopically: 5cm long vermiform appendix, with pseudomembranes on serosal surface Dg: Acute appendicitis with periappendiceal abscess
March 2017 Rapid increase of abdominal circumference, epigastric & lumbar pain Biologically: hepatic cytolysis, cholestasis, increase lipase & LDH Imaging (CT, TEP-scan): mesenteric mass 19cm (SUV-18) nodules (3-5 cm) peritoneal, perihepatic, Douglas s pouch diffuse GI wall hyperfixation (SUV- 11) (stomach, jejunum) thyroid nodules inferior vena cava thrombosis, ascites
Clinicians asked for a retrospective histopathological review of the appendix
Some reflections. What is your dg? How many of you would agree with the dg of acute appendicitis? Would you ask for further IHC? If yes, which antibodies?
CD20 CD5
CD20 CD5
CD10 Bcl-6 MUM1 Hans algorithm
p53 p21 Ki-67 Bcl- 2 cmyc
BL/DLBCL morphology BL-like phenotype BL HGBCL, NOS HGBCL w R MYC+BCL2+/-BCL6 DLBCL, NOS FISH studies NO MYC/8q24; BCL2/18q21, BCL6/3q27 gene rearrangments Revised diagnosis Primary appendicular DLBCL, NOS GC phenotype (Hans algorithm) FISH 8q24 break-apart probe Absence of MYC translocation, fusion signal pattern
Apr 2017: Core needle biopsies of mesenteric mass were performed to confirm the dg
CD20 CD3
Further clinical work-up Flow cytometry peripheral blood and bone marrow - negative for lymphoma Bone marrow biopsy absence of infiltration Cytology LCR - negative Ann Arbor Stage IV (digestive, peritoneal) aaipi 2 (LDH, Stage)
Follow-up Apr 2017: COP treatment for debulking (remarkable regression of tumor mass) R-COPADEM, FISH results neg switched to R-CHOP 14 (GAINED study) No ovarian cortex cryopreservation (emergency treatment) May 17 PET scan Sept 2017 CR CR 13 months after ASCT Aug 17
Journal of Surgical Research 2017 Rare, <250 cases, 1.7% of appendiceal tumors Mean age 48y (range 4-70), M:F - 1.5:1, most White Most pts no relevant medical history, immunocompetent Non-specific clinical findings, often signs and symptoms suggestive of acute appendicitis Right hemicolectomy confers no survival benefit over appendectomy CHT primary treatment modality
CT scan Markedly homogeneous enlargement (2.5-4cm) of the appendix Usually preserved vermiform morphology Stranding of the periappendiceal fat : superimposed inflammation or tumor extension Coexisting abdominal LAD or aneurysmal dilatation of the appendiceal lumen specific for lymphoma Pickhardt et al AJR Am J Roentgenol. 2002 Contrast enhanced CT Axial images from unenhanced CT
Pathological examination Diffuse, circumferential wall thickening w obliteration of the lumen Diffuse lymphocytic infiltration of the appendiceal wall Periappendiceal inflammation, necrosis, and/or lymphomatous extension into adjacent fat Lymphoma types: DLBCL (34%), BL (26%, young age), FL (15%) Pickhardt et al AJR Am J Roentgenol. 2002 Ayud et al. J Surg Res 2017
Take home message Primary lymphomas of the appendix exist and can affect young pts All appendectomies should be sent for HP dg Appendix with >2.5 cm diameter suspicious for neoplasm extensive sampling Awareness is crucial to achieve the correct dg; clinical signs of appendicitis, young age and acute inflammation are pitfalls in recognizing lymphomatous appendiceal involvement