California Tumor Tissue Registry
Case of the Month
July, 2003
A 63-year-old male presented with a persistent sore throat and
was noted to have an enlarged right tonsil. A four cm oval
tonsil was excised. The patient’s history was noteworthy for
his having received a kidney transplant five years earlier. Up
to this time his immunosuppressant treatment had been
uneventful.
Fig. 1: Tonsillar tissue showed architectural distortion by sheets of eosinophilic structures.
Fig. 2: The structures were be variably sized, consisting of homogeneous eosinophilic material in
both cytoplasmic and nuclear locations. The cytoplasmic structures were felt to represent Russell
Bodies and the rarer nuclear ones were felt to be Dutcher Bodies.
Fig. 3: A CD79a immunostain highlighted a population of plasma cells.
Fig. 4: Kappa (left, 4a) was negative while Lambda (right, 4b) was positive.
PAS and CD138 stains were positive. A CD117 was positive in a few of the plasma cells.
Negative stains included CD20/CD3, Congo red, and Crystal violet.
Diagnosis:
“Post Transplant Lymphoproliferative Disorder - Plasmacytoma Type, With
Prominent Russell Body and Dutcher Body Formation”
Sajjad P Syed, MD, Jung Wang, MD, William P Illig, MD, and
Donald R Chase, MD


Loma Linda University Medical Center, and California Tumor Tissue
Registry, Loma Linda, California, USA.
Midwest Pathology Consultants, P.C., Oklahoma, USA.
Since 1969, it has been well established that organ transplant recipients have an increased
incidence of neoplasms, especially skin and lip carcinomas, as well as lymphoid lesions. The
latter conditions are usually B-cell proliferations, with many being Epstein Barr Virus (EBV)
related. They cover a complex spectrum ranging from reactive lymphoid hyperplasia to
lymphoma (1). The clinically and histologically heterogenous group of EBV-driven lymphoid
proliferations that arise following solid organ transplantation are collectively referred to as posttransplantation lymphoproliferative disorders (PTLD). Twenty percent (20%) of these, however,
have been found to be EBV-negative, and among renal allograft recipients up to 50% may not be
associated with EBV. EBV-negative cases tend to occur later than EBV-positive cases (usually >
CTTR’s Case of the Month
July, 2003
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5 years after transplant) (9). Using serology, 93 percent of post-transplant patients in the
University of Pittsburgh study had EBV (3). PTLDs occur more frequently in children than in
adults (2). Patients who have undergone heart-lung transplantation are reported to have the
highest incidence and shortest interval of development of PTLD (9.4 %), whereas patients
receiving kidney transplants have the lowest incidence and longest interval of development
(approx. 1%) (3). Donor origin PTLDs appear to be most common in liver and lung allografts
(9). The variable incidence of PTLD has been attributed to the different intensities of
immunosuppression needed for the different types of allografts. Patients who have undergone
more than one transplant have a higher likelihood of developing PTLD. Agents associated with
the development of PTLD include: cyclosporine A (6), tacrolimus, OKT3 antibody, and
azathioprine or antilymphocyte globulin (3). The interval between transplant and development of
PTLD is relatively short with a mean interval of 48 months having been described in literature.
Some cases have been reported as early as 0.7 months (3).
The majority of PTLDs occur in extranodal locations. The patients generally fall into three
categories:



those with head and neck disease, who present with either as a mononucleosis-like illness
with fever, sore throat with tonsillar enlargement and lymphadenopathy, or a localized
mass (5),
those with abdominal disease, usually secondary to involvement of the gastrointestinal
tract with ulceration or perforation, and
those with single organ involvement, the central nervous system being the most common
site (3).
According to the WHO classification, PTLD is categorized from ‘early lesions’ to ‘overt
lymphomas’(9):
1. Early lesions
 Reactive plasmacytic hyperplasia
 Infectious mononucleosis-like proliferations
2. Polymorphic PTLD
3. Monomorphic PTLD (classified according to lymphoma classification)
B-Cell neoplasms
 Diffuse large B-cell lymphoma (immunoblastic, centroblastic, anaplastic)
 Burkitt/Burkitt-like lymphoma
 Plasma cell myeloma
 Plasmacytoma-like lesions
T-Cell neoplasms
 Peripheral T-cell lymphoma, NOS
 Other types
4. Hodgkin lymphoma (HL), and Hodgkin-like PTLD
The presence of plasmacytic elements is considered a hallmark of PTLD, and in a transplant
recipient a predominance of these cells within an infiltrate should suggest PTLD rather than a
nonspecific inflammation of another cause (1). The rare PTLD plasmacytoma-like lesion is
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characterized by a proliferation of monomorphic B-cells and morphologically is similar to
plasmacytomas which arise in non-transplantation settings. In general, plasmacytomas may be
subclassified into four groups based on location:




extramedullary (extraskeletal),
solitary plasmacytoma of bone,
multiple myeloma, and
plasma cell leukemia (4).
Post transplant plasmacytoma-like lesions are almost always extramedullary, usually occurring in
the gastrointestinal tract, extranodal locations, lymph nodes, or other sites (9).
In non-immunocompromised patients who develop plasmacytoma de novo, the median age is 5070 years. Men are affected three to four times as often as women. Although extramedullary
plasmacytomas have been reported in almost every organ (including skin), primary involvement
of a lymph node is rare (4). Between 80-90% of extramedullary plasmacytomas occur in the head
and neck, primarily in the upper respiratory tract, especially the nasal cavity (25–30 %), paranasal
sinus (20–25 %), nasopharynx (20–25 %), tonsil (5–10 %), larynx (5 %), and oral cavity (5 %).
The latter includes the gingiva, submaxillary and parotid gland, and the roof of the mouth. In the
setting of organ transplant, findings of masses in the Waldeyer’s ring or an excessive number of
cervical nodes should increase the index of suspicion of PTLD (7). Children without previous
EBV exposure may develop PTLD localized to the tonsils/adenoids, and biopsy of these tissues
may permit early diagnosis and clinical intervention (8). Post transplant plasmacytoma of the
heart is reported to have the worst outcome (10).
When involving the G.I. tract, PTLD is usually submucosal, and is from two to five cm in
greatest diameter. It is usually red, soft or firm, and either sessile or pedunculated. It tends to
bleed easily. Extraosseous tumors rarely show destruction of adjacent bone (4).
Histologically, PTLDs are fairly uniform, consisting of a dense, homogenous infiltrate of plasma
cells. These plasma cells have been shown to be clonal, though polyclonal proliferations exist.
They may demonstrate varying degree of atypia, including prominent nucleoli, dispersed
chromatin, irregular nuclei, and multinucleation (4). Three variants have been described:



The plasmacytic (well-differentiated) variant consists of plasma cells having clumped
chromatin and little cytologic dysplasia.
The plasmablastic (moderately differentiated) type, consists of plasma cells having more
dispersed chromatin and more prominent nucleoli. The cytoplasm is more amphophilic
than a normal plasma cell.
The anaplastic (poorly differentiated) type has more nuclear immaturity and dysplasia
(4).
Immunoglobulin inclusions in the cytoplasm (Russell bodies) or nuclear psuedoinclusions
(Dutcher bodies) can be present in all more-differentiated types of plasmacytomas. In our
presentation case, the most striking feature was the remarkably overwhelming presence of
immunoglobulin inclusions (Russell bodies), which nearly completely replaced the native cells.
Rarely, amyloid or amorphous deposits of immunoglobulin, sometimes accompanied by a foreign
body reaction, may be seen (4).
Immunohistochemistry shows the plasma cells to be surface immunoglobulin negative. They do,
however, contain immunoglobulin in their cytoplasm. Most B-cell antigens are negative (CD19,
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CD20, CD22), but CD79a may be positive. Other markers which are variably positive include
CD45, HLA-DR, CD38, EMA, CD43, and CD56 (4). Immunoglobulin heavy-chain and lightchain genes have been shown to be rearranged or deleted, and to show variable regional
mutations similar to post-germinal center cells (1). In recent molecular studies, EBV does not
appear to be of major importance in the pathophysiology of extramedullary plasmacytoma(4).
If untreated, PTLDs of either polyclonal and monoclonal type often have a rapid progressive,
even fatal clinical course (3), with overall mortality in solid organ allograft recipients being
approximately 60%. If progression occurs, the tumor is usually treated as a lymphoma, with
standard therapies such as irradiation and chemotherapy being utilized (3). Acyclovir, a drug that
inhibits EBV DNA replication, has sometimes been given with varying success, but its use in
extramedullary plasmacytoma is not clear. Radiotherapy has been shown to be an effective
treatment for primary extramedullary plasmacytomas. To prevent PTLD from developing in
patients who will receive bone marrow transplant, pre-transplant depletion of B cells from the
donor marrow prior to infusion may be considered (1). Of some interest is that if
immunosuppressive therapy is withdrawn or substantially reduced, some PTLDs have been
shown to completely regress.
With early diagnosis, prompt reduction of immune suppression, and careful administration of
chemotherapy or radiation therapy, the prognosis for all types of PTLD has improved (9).
References
Neoplastic Hematopathology, 2nd Ed. Knowles. Pgs.117, 524, 579-595, 702, 720-721, 1048-1052,
1217-1218, 1292-1292, 1339-1341
2. Immunodeficiency Disorders. Pediatric Hematopathology, Collin & Swerdlow. Pgs.48-57
3. Surgical Pathology of the Lymph Nodes and Related Organs, 2nd Ed. Jaffe. Pgs.325-330, 527
4. Surgical Pathology of the Head and Neck, Vol 2, 2nd Ed. Leon Barnes. Pgs.1323-1329
5. Hague et al. Posttransplant Lymphoproliferative Disease Presenting as Sudden Respiratory Arrest
in a Three Year Old. Ann Otol Rhinol Laryngol 1997 Mar;106(3):244-7.
6. Nalesnik et al. The Pathology of Posttransplant Lymphoproliferative Disorders Occurring in the
Setting of Cyclosporine A – Prednisone Immunosuppression. Am J Pathol 1988 Oct;133(1):17392.
7. Loevner et al. Posttransplantation Lymphoproliferative Disorder of the Head and Neck: Imaging
Features in Seven Adults. Radiology 2000 Aug; 216(2):363-9.
8. Lones et al. Changes in Tonsils and Adenoids in Children With Posttransplant
Lymphoproliferative Disorder: Report of Three Cases With Early Involvement of Waldeyer’s
Ring. Hum Pathol 1995 May;26(5):525-30.
9. Tumors of Haematopoietic and Lymphoid Tissues. Elaine S. Jaffe, Nancy Lee Harris, Harold
Stein, and James W. Vardiman. WHO, 2001. Pgs.264-271
10. Fernandez LA, Couban S, Sy R, Miller R. An Unusual Presentation of Extramedullary
Plasmacytoma Occurring Sequentially in the Testis, Subcutaneous Tissue, and Heart. Am J
Hematol 2001 Jul;67(3):194-6.
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