CD-30 Positive Peripheral T-cell Lymphoma of the Waldeyer's Ring

We describe a patient with peripheral T cell lymphoma of the Waldeyer's ring that ran a highly aggressive course. This is followed by a discussion on the differential diagnoses of nasal T/NK cell lymphoma and Ki-1 ALCL, based on clinical and pathological features.

Keywords: peripheral T cell lymphoma. Ki-1 ALCL, nasal T/NK cell lymphoma, ALK1

CD30 (Ki-1) is a 120-KD transmembrane protein with the extracellular domain homologous to that of the tumor necrosis factor receptor superfamily.[1] It is a lymphocyte activation marker initially identified in Reed-Sternberg cells in Hodgkin's disease (HD) and subsequently also found in a subgroup of diffuse large cell lymphoma with very large pleomorphic bizarre cells. The latter was subsequently designated as Ki-1 positive anaplastic large cell lymphoma (ALCL).[2] Extranodal involvement, especially of the skin, occurs in up to two-thirds of patients in Ki-1 ALCL.[3,4] However, CD30 is not specific for HD and Ki-1 ALCL and is also expressed in other types of non-Hodgkin's lymphoma (NHL), especially those of T-cell lineage.[5]

Primary NHL of the Waldeyer's ring are usually of B-lineage[6] while the majority of NHL of the nose and nasopharynx are of T-cell in lineage.[7,8] Here we describe a patient with peripheral T-cell lymphoma of the Waldeyer's ring, which ran an extremely aggressive clinical course. The overlap with nasal T/NK cell lymphoma and Ki-1 ALCL with respect to the clinical, histological and immunophenotypic features will be discussed.

A 42-year-old man presented with a two-month history of sore throat, intermittent fevers and weight loss of 3 kilograms. A nasal endoscopy revealed tumorous growth in the right nasopharynx and ulcerated erosion of the soft palate (Fig. 1). Physical examination showed fever and two right cervical lymph nodes measuring 1 cm in diameter. MR imaging showed soft tissue swelling in the right lateral wall of the oro- and naso-pharynx including the right palatine tonsil (Fig. 2). Biopsy of the tumor showed diffuse infiltration by large lymphoid cells with a heavy admixed population of small lymphocytes (Fig. 3). These cells were positive for CD3 and CD30 (Fig. 4) but were negative for CD56, ALK1 and B cell markers. Angiocentricity was not a feature. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was negative. This lymphoma was, therefore, interpreted as CD30-positive peripheral T-cell lymphoma.

Investigation showed hemoglobin of 11.8 g/dL (Normal range: 11-15 g/dL), platelet count of 163 x 109/L (NR: 150 - 400 x 109/L) and leukocyte count of 7.5 x 109/L (NR: 4 - 11 x 109/L). Serum sodium, potassium, urea, creatinine, transaminase levels were within normal limits. Serum albumin was 36 g/L (NR: 42-54 g/L) and lactate dehydrogenase level was 545 u/L (NR: 200-400 u/L). Serology for HIV was negative. Computerized tomography of the thorax and abdomen were normal. Bilateral trephine biopsies revealed normal hemopoiesis and no evidence of lymphoma involvement. The disease and B symptoms remained refractory to CEOP (cyclophosphamide 650 mg/m2 D1, epirubicin 60 mg/m2 D1. vincristine 1.4 mg/m2 D1 and prednisolone 100 mg/d DI-5), ProMACE-Cyta-BOM (prednisone, cyclophosphamide, methotrexate, cytarabine, etoposide, bleomycin, vincristine) and local radiotherapy (40Gy). The patient died of progressive, disseminated disease involving the Waldeyer's ring and the liver four months after diagnosis.

Waldeyer's ring is one of the common primary sites of extranodal NHL. The architecture of most primary NHL of Waldeyer's ring is diffuse and majority are large-cell of B lineage[6] in contrast to the T-lineage of our case.

As the disease in our patient involved the naso-pharynx (part of the Waldeyer's ring) and was extremely aggressive clinically, it resembled nasal T/NK cell lymphoma which is similarly aggressive.[8,10] However, nasal T/NK cell lymphoma often exhibits angiocentricity and zonal necrosis, and is CD56 positive, surface CD3 negative and EBER positive in contrast to our case. Besides. nasal T/NK cell lymphoma primarily involves the nasopharynx and nose.[8,11] In contrast, the main bulk of tumor in the current case was in the oropharynx and palatine tonsil, as evidenced by MR imaging. However, as the tumor cells were CD30-positive, differential diagnoses included Ki-1 ALCL and Hodgkin's disease. The absence of classical Reed-Sternberg cells and their variants, and the expression of CD3 in our patient excluded the diagnosis of Hodgkin's disease.

Ki-1 (CD30+) ALCL is classified as a distinct clinicopathological entity in both the updated Kiel Classification and the REAL classification.[12] Primary systemic Ki-1 ALCL often harbors t(2;5)(S535, 2p23) and the expression of the resultant fusion protein NPM-ALK is detectable in up to 60-85% of cases by anti-ALK antibodies such as p80, ALK1 or ALKc.[13-15] One-half to two-thirds of patients with Ki-1 ALCL are of T cell phenotype,[3,4] and "hallmark cells", which are large-sized with prominent nucleus and inclusion-like nucleoli, are usually present.[13,14] Although our case was CD30 positive, it was negative for ALK1 and hallmark cells were absent. Besides, patients with Ki-1 ALC fare better than other types of aggressive lymphoma of both Band T-lineage with a very favorable 5-year failure-free and overall survival of 58% and 77% respectively.[16] In contrast, our patient pursued a rapidly downhill course despite the limited disease stage and intensive chemoradiotherapy.

Recent studies showed that Ki-1 ALCL encompasses a wide morphologic spectrum, including many cases that show neither large or anaplastic morphology.[13,14.17] However, in cases which are ALK1 negative, presence of hallmark cells is required in order to be classified as ALK1 negative ALCL.[13] Our case, despite the expression of CD30, was negative for ALK1 and "hallmark" cells were absent. Therefore, it was diagnosed as PTCL. Besides, the extremely aggressive clinical course in our patient was indeed much more consistent with a PTCL than a Ki-1 ALCL.

In conclusion, our patient is unique in that he had a CD-30 positive peripheral T cell lymphoma of the Waldeyer's ring. Clinically it resembled nasal T/NK cell lymphoma in the nsopharyngeal involvement and the aggressive clinical course, and immunophenotypically it overlapped with Ki-1 ALCL because of the expression of CD30. This case illustrates the usefulness of CD30 in the diagnosis of Ki-1 ALCL but also the potential confusion as CD30 is not specific to Ki-1 ALCL and also demonstrates the evolving diagnostic criteria employed as a result of new data obtained from anti-ALK immunohistochemistry studies.

Leukemia and Lymphoma, 2000, Vol. 38(1-2), pp. 165-3

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PHOTO (BLACK & WHITE): FIGURE 1 Clinical photograph showing the necrotic ulcer in the right palatine tonsil and soft palate (See Color Plate XIII at the back of this issue)

PHOTO (BLACK & WHITE): FIGURE 2 (a) An axial T2-weighted scan of the oropharynx shows a hyperintense soft mass revolving the right lateral oro-pharyngeal wall including the palatine tonsil (arrows); (b) A T1-weighted scan more superiorly in the nasopharynx shows extension of disease to the right lateral pharyngeal wall (arrowheads)

PHOTO (BLACK & WHITE): FIGURE 3 (a) A dense inflammatory infiltrate in the nasopharynx. The neoplastic lymphoid cells are medium sized with occasional nucleolus. (H & E, x 85): (b) there is an admixed population of small lymphoid cells. (H & E, x 200) (See Color Plate XIV at the back of this issue)

PHOTO (BLACK & WHITE): FIGURE 4 The tumor cells show membranous and occasionally paranuclear Golgi staining of CD30. (x 300) (See Color Plate XV at the back of this issue)

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