Feline Hodgkin's-like lymphoma (a review of 20 cases)

©R. M. Walton and M. J. Hendrick Feline Hodgkin's-like Lymphoma: 20 Cases (1992–1999) Vet Pathol 38:504-511 (2001) http://www.vetpathology.org/cgi/content/full/38/5/504

In general, Hodgkin's disease (HD) in humans differs clinically from non-Hodgkin's lymphoma in several ways.1,6 In contrast to non-Hodgkin's lymphoma, HD typically involves a single axial group of nodes and spreads contiguously, and extranodal involvement is uncommon. The nature of HD is manifest as a minority of neoplastic cells, approximately 1–5% of cells in affected tissue,1,17 against a background of lymphocytes, macrophages, neutrophils, and eosinophils. Diagnosis and subclassification of HD therefore necessitates histologic evaluation of whole affected nodes and fine needle aspirate cytology is of limited use.

In humans, the importance of properly diagnosing HD lies in treatment and prognosis. Treatment modalities differ from conventional chemotherapeutic protocols for non-Hodgkin's lymphoma. Dependent upon clinical staging, surgical excision and/or radiation therapy may be primary treatment strategies.6 In contrast to most types of non-Hodgkin's lymphoma, HD is currently considered a curable neoplastic disease depending upon the stage at which it is diagnosed.1

The cases in this report conform to many of the histomorphologic criteria of HD as elaborated for humans. The tumours all consisted of a minority population of putative neoplastic cells within a background of small lymphocytes, histiocytes, and granulocytes. Subclassification schemes of human HD are predicated upon the presence of classic RS cells or L+H cells.1,6 The L+H cells are present only in the LPHD subtype, whereas classic binucleate RS cells and mononuclear or multinucleate variants are found in mixed cellularity HD, and lacunar cells and smaller numbers of classic RS cells or RS nuclear variants are characteristic of nodular sclerosis HD. For the most part, our cases conformed to these criteria. However, the feline tumours diverged from HD subclassification schemes in the following ways: 1) classic RS cells were scarce in cases of feline mixed cellularity and nodular sclerosis HD relative to human HD, 2) L+H cells were found in conjunction with classic RS cells/RS cell variants in mixed cellularity and nodular sclerosis, and 3) lacunar cells were noted in small numbers in LPHD.

The clinical presentation is unusual for feline lymphoma and appears very similar to that of human HD. In 95% (19/20) of cases, the cats were presented with either a single enlarged lymph node (17/20) or two contiguous enlarged lymph nodes (2/20). However, in all except six cats (Nos. 2–4, 18–20), internal/extranodal involvement was only assessed via palpation. No necropsies were available for any of the cats that were euthanatized, precluding accurate assessment of clinical progression. Further work is necessary to better characterize the clinical progression of feline HD to determine whether disease progression and biologic behaviour is indeed similar to that of human HD.

In the 20 cats evaluated, differences existed with respect to subtypes and sex predilection as compared with human HD. In humans, the nodular sclerosis subtype comprises 65–75% of HD cases, whereas 90% (18/20) of feline Hodgkin's-like disease cases fell into mixed cellularity (9/20) or lymphocyte predominance (9/20) categories. Unlike our findings for feline HD, males are overrepresented in all human HD subtypes except nodular sclerosis. However, the absence of a sex predilection in these cats is based upon a relatively small sample size.

Except for L+H cell variants, immunohistochemical staining of RS cells and RS variants in human HD has yielded diverse and inconsistent results.7 The emerging consensus of the identity of the RS cell and variants has largely been derived from genotypic analyses of T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements, which suggest a cell of lymphoid origin.5,7,8,11,20 Immunophenotypic and immunohistochemical studies of L+H cells consistently indicate a B-cell identity,11 but RS cells and RS variants in the mixed cellularity and nodular sclerosis subtypes are of less certain origin.4,7,8 Using a limited panel of markers, our findings suggest a B-cell phenotype (BLA.36+ and CD79a+) for the L+H cells in feline LPHD. None of the classic RS cells or mononuclear, multinucleate, or lacunar variants stained with CD79a, BLA.36, CD3, or MAC387 antibodies, a finding analogous to that for human HD.

A primary differential diagnosis that should be considered for HD is T-cell-rich B-cell lymphoma (BCL), a variant of BCL characterized by a minority of neoplastic B-cells (<=10%) in a reactive T-cell background.2,15 In humans, the importance of identifying T-cell-rich BCL is to distinguish it from HD or T-cell lymphoma, which are treated differently and have different prognoses. In one report, reclassification of 5% of LPHD diagnoses to T-cell-rich BCL was made on the basis of absence of characteristic L+H cells and transformed germinal centers. Furthermore, these patients presented with an aggressive and advanced stage of disease, which is very unusual for LPHD.2 Misdiagnosis of T-cell-rich BCL as HD occurred in 5% and 26% of cases in two studies, respectively.2,15 This diagnostic dilemma appears to present confusion in the veterinary literature as well. A series of eight cases of feline lymphadenopathy whose "clinical, histological, and immunophenotypic findings ... were identical with those of ‘nodular lymphocyte predominance (lymphocytic and histiocytic/L+H) Hodgkin's disease’ in man" was reported.3 However, the report was entitled, "T-cell-rich B-cell lymphoma in the cat." Similarly, the first report of T-cell-rich BCL in a cat has a clinical presentation and histologic features that might suggest HD rather than T-cell-rich BCL.19 The authors argued that the absence of classic RS cells precludes a diagnosis of HD; however, the description of the histology would suggest an LPHD subtype, characterized by the presence of L+H cells and marked paucity or absence of classic RS cells.

Other differential diagnoses to be considered for peripheral lymphadenopathy in the cat would include distinctive peripheral lymph node hyperplasia of young cats13 (DPLH) and generalized lymphadenopathy resembling lymphoma.12 DPLH may be distinguished clinically from HD by the age of onset (<=2 years) and the transient nature of the adenopathy. Histologically, the nodes are characterized by a mixture of histiocytes, lymphocytes, plasma cells, and "immunoblasts" that encroach upon and even efface lymphoid follicles; however, atypical lymphoid cells conforming to RS cells or RS variants have not been reported. Six of nine cats with DPLH tested positively for FeLV.13 As the name implies, the clinical presentation of generalized lymphadenopathy resembling lymphoma is not consistent with HD; the adenopathy also proves to be transient. Furthermore, histologic evaluation of the affected nodes reveals variable loss of normal architecture by a homogeneous population of lymphoid cells and lack of atypical RS cells or RS variants.12

In this report, preliminary clinical information suggests that feline Hodgkin's-like lymphoma may be a less aggressive neoplasm than non-Hodgkin's feline lymphoma. Eleven of the cats for which information was available received no treatment. Survival times in untreated cats were at least 7 months and as long as 4 years with the exception of three cats that were euthanatized at the owner's request or as a result of another disease and one cat that was lost to follow-up after 3 months. These findings are similar to those reported previously in which there was no recurrence of disease in three of eight cats after 6 months with no treatment, and one of eight cats survived for 12 months with no treatment other than excision of the affected node.3 One cat survived for at least 28 months with no treatment other than surgical excision of the affected node.19 To establish whether Hodgkin's-like lymphoma behaves less aggressively than non-Hodgkin's lymphoma in cats, statistical analysis of survival data is needed and results should be compared with published survival data for feline non-Hodgkin's lymphoma.

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