dodo Case 18 A 56 year old male presented with lesions on the forearms. Lesions initially responded to steroids, but then recurred. T-cell gene rearrangement was positive. IgH gene rearrangement was negative.

CD3

No rimming around fat spaces

CD20

PD-1/CD279 CD10 T-FH phenotype: Explains the presence of numerous B-cells In a T-cell lymphoproliferative disorder (Rodriguez-Pinilla et al. Am J Surg Pathol, 2009

Case 18 Diagnosis: Primary cutaneous CD4-positive small/medium T-cell lymphoma / lymphoproliferative disease

Primary cutaneous CD4 positive small/medium T- cell lymphoma (Provisional entity WHO 2008)

Primary Cutaneous T & NK Cell Neoplasms (2008) Mycosis Fungoides Sezary Syndrome Primary cutaneous anaplastic large-cell lymphoma Primary cutaneous gamma-delta T-cell lymphoma Primary cutaneous aggressive epidermotropic CD8 positive cytotoxic T-cell lymphoma* Primary cutaneous small/medium CD4 positive T-cell lymphoma* Hydroa vacciniforme-like lymphoma * provisional

Primary cutaneous small/medium CD4 positive T-cell lymphoma vs. Pseudolymphoma Beltraminelli et al Am J Derm patientsMedian Age 53 (3-90) All but three lesions were solitary –75% head and neck area TCR gamma clonal 60% Excellent prognosis –41/45 (91%) NED, median follow up 63 months –4/45 (9%) alive with cutaneous disease –Treatment not discussed Proposal: cutaneous nodular proliferation of pleomorphic T- lymphocytes of undetermined significance

Other clinical series Grogg et al. Mod Pathol 2008 (15 pts) –14/15 single lesion –Sole patient with multiple lesions had progressive disease following chemo/ stem cell transplant Garcia-Herrera et al. JCO 2008 (24 pts) –16 pts, localized disease, CR 14/16, no deaths –5 pts, aggressive disease, bulky tumors (>5cm), high Ki-67; 5/5 DOD; median survival, 23 mos. –3 pts, prominent eosinophilia, varied course

Primary cutaneous CD4 positive small/medium T- cell lymphoma (Provisional WHO 2008) For patients with isolated cutaneous lesions, alternative terminology may be warranted: Cutaneous CD4+ T-cell lymphoproliferative disorder of undetermined significance.

Clonal T-cell LPDs of low or indeterminate malignant potential Indolent CD8+ lymphoid proliferation of the ear (Petrella et al, 2007) –Dense, non-epidermotropic; Clonal –Rx with local radiotherapy or excision –Local recurrence in some, but no progression –Also involves other acral cutaneous sites

CD8 38 yo. male with lesion of ear

Indolent CD8+ T-cell LPD of GI tract “Low grade intestinal T-cell lymphoma” “Cytotoxic T-cell lymphoproliferative disease” “Lymphomatous polyposis of T-cell type” –Carbonnel 1994; Egawa 1995; Hirakawa 1996 –Ranheim 2000; Isomoto 2004 Multiple mucosal and intestinal sites Relapsing but non-progressive

Indolent T-cell lymphoproliferative disease of the gastrointestinal tract – A report of 10 cases Perry AM et al. Colon

CD8 38 yo male with lesions of stomach, sm bowel, colon over 2 yrs No invasion of epithelium

Indolent T-cell lymphoproliferative disease of the GI tract (10 cases) Perry et al. Ages (median 48), M:F 6:4 Oral cavity, stomach, small intestine, colon, esophagus (1) Diarrhea, pain, rectal bleeding –“Crohn’s disease (2 patients), Colitis Follow-up: months; Median 38 months –2 pts followed >10 yrs 6 patients received chemotherapy for PTCL, with no response

Indolent T-cell LPD of the GI tract Immunophenotype/ Genotype 8 cases: CD8+/CD4- –1 case CD4+/CD8-; 1 case CD8-/CD4- TCR beta pos/ TCR gamma neg (6 tested) Proliferation rate: <10% 10/10: Clonal PCR TRG EBV negative

Oral Bx 1999 Intestine 2012 TCR gamma PCR – Two lesions 13 years apart

Superficial infiltrate Confined to mucosa No invasion of the wall Very low proliferation rate No destruction of the glands No cytological atypia Very bland infiltrate Ki-67 ? Optimal management Do not respond to chemorx

Indolent CD8+ T-cell LPD of GI tract Perry et al. Blood 203 Important to distinguish from EATL and other intestinal T-cell lymphomas –Indolent and non-progressive clinical course –Optimal therapy uncertain; do not respond to conventional chemotherapy Etiology underdetermined – may be related to antigen drive Relationship to inflammatory bowel disease uncertain Similar in phenotype and clinical behavior to CD8+ LPD of the “ear”

NK-cell Enteropathy An atypical proliferative lesion mimicking lymphoma Mansoor, A., S. et al. Blood 117: , cases: M:F 1:3; Median age 49 (27-70) Vague GI symptoms, but negative for celiac disease Superficial lesions with hemorrhage, edema, ulceration Lesions in stomach, small intestine, and colon

Colon: Endoscopy and Immuno-Histology (CD3)

CD56 Colon biopsy

Immunophenotype: NK-cell Enteropathy (8 cases) CD56 strongly + TIA-1+/ GrB+ cCD3+, CD7+, CD2 variable T-cell ag negative: CD4, CD8, CD5, BF1 PCR neg for TCR gene rearrangement EBV-negative PB and BM: normal in pts studied

NK-cell enteropathy is a indolent disease of unknown etiology Similar cases reported by Takeuchi et al. in stomach This could represent an immune response to an unknown pathogen The cytological atypia and CD56+ often leads to a mistaken dx of NK-cell or T-cell lymphoma Be cautious about making the diagnosis of lymphoma on superficial biopsies