522 Am J Clin Pathol 2006;126:522-529

522 DOI: 10.1309/AFHA406GBT0N2Y64

American Society for Clinical Pathology
Hematopathology / TRAUMATIC ULCERATIVE GRANULOMA
Traumatic Ulcerative Granuloma With Stromal Eosinophilia
A Reactive Lesion of the Oral Mucosa
Abraham Hirshberg, MD, DMD,
1
Ninette Amariglio, PhD,
2
Sharon Akrish, DMD,
1
Ran Yahalom, DMD,
3
Hanna Rosenbaum, MD,
4
Elimelech Okon, MD,
5
and Ilana Kaplan, DMD
5
Key Words: Traumatic ulcer; Clinical pathology; Hematology; Eosinophilic ulcer; CD30; Anatomic pathology, head and neck; Lymphoma;
Traumatic ulcerative granuloma with stromal eosinophilia
DOI: 10.1309/AFHA406GBT0N2Y64
A b s t r a c t
Traumatic ulcerative granuloma with stromal
eosinophilia (TUGSE) is a benign lesion of the oral
mucosa of an unclear pathogenesis. We analyzed the
profile of the inflammatory infiltrate in 12 cases of
TUGSE by using immunohistochemical analysis and
polymerase chain reactionbased repertoire analysis to
detect T- and B-cell receptor gene rearrangements. The
inflammatory infiltrate consisted in most cases of B and
T lymphocytes, macrophages, abundant eosinophils,
and large atypical cells. In 5 cases, CD30+ cells were
found. Spectratyping analysis displayed a polyclonal
rearrangement of the T-cell receptor gene in 6 cases
and oligoclonality in 5 cases. Monoclonality was
observed in 1 case that also fulfilled histologic criteria
for lymphoma. Healing was uneventful in all cases,
including the one suspected of being lymphoma, with no
recurrences in more than 2 years follow-up. TUGSE
can be regarded as reactive. Some cases, however, may
harbor a dominant clonal T-cell population; in these
cases, long-term follow-up is mandatory.
Traumatic ulcerative granuloma with stromal eosinophilia
(TUGSE) is a chronic, benign, self-limiting lesion of the oral
mucosa, manifesting as an ulcer with elevated margins. The
most common location is the tongue, although other locations in
the oral mucosa are possible.
1
Various terms have been used to
describe TUGSE, including eosinophilic ulcer, eosinophilic
granuloma of soft tissue, ulcerative eosinophilic granuloma, and
traumatic ulcerative granuloma with stromal eosinophilia.
1-10
In
infants, TUGSE is called Riga-Fede disease.
2
Histologically,
TUGSEs show a diffuse polymorphic inflammatory infiltrate,
rich in eosinophils, involving the superficial mucosa and the
deeper muscle layer. Atypical large mononuclear cells scattered
within the inflammatory infiltrate have been described in some
cases, thus the term, atypical histiocytic granuloma.
11
The pathogenesis of TUGSE is controversial. Although
trauma was considered to have a major role in its pathogenesis,
obvious trauma could not be demonstrated in most cases.
It has been suggested that TUGSE may be a CD30+ lym-
phoproliferative disease.
12,13
Alobeid et al
13
found T-cell mono-
clonality in 3 cases by using immunohistochemical and poly-
merase chain reaction (PCR) analysis and suggested that the oral
lesions seemed to be the counterpart of the spectrum of primary
cutaneous CD30+ lymphoproliferative disorders.
The aim of the present study was to analyze the phenotypic
and genotypic profile of the inflammatory infiltrate of TUGSE
by using immunohistochemical analysis and PCR-based reper-
toire analysis for T- and B-cell receptor gene rearrangements and
to discuss the pathogenesis and outcome of these cases.
Materials and Methods
The archives of the oral pathology laboratory at the School
of Dental Medicine, Tel Aviv University, Tel Aviv, Israel, were
Am J Clin Pathol 2006;126:522-529 523
523 DOI: 10.1309/AFHA406GBT0N2Y64 523
American Society for Clinical Pathology
Hematopathology / ORIGINAL ARTICLE
reviewed for TUGSE cases diagnosed between January 2000
and December 2004. Only cases with detailed clinical informa-
tion (age, sex, clinical diagnosis) and follow-up information
were used for the study.
The diagnosis of TUGSE was based on clinical and histo-
logic features that included the presence of an ulcer with a poly-
morphic inflammatory infiltrate intermixed with eosinophils.
The infiltrate extends into the deeper tissues.
Formalin-fixed, paraffin-embedded biopsy material from
12 TUGSE cases was included in the study. We cut 5-m-thick
sections from each case. One slide was stained with H&E to ver-
ify the diagnosis and evaluate the inflammatory infiltrate.
Additional sections were mounted on charged glass slides and
processed for immunohistochemical analysis, and 5 sections
were submitted for PCR analysis.
Immunohistochemical Analysis
Table 1 lists the monoclonal antibodies used in this study.
Immunohistochemical analysis was performed according to
standard procedures. Briefly, sections were deparaffinized in
xylene and hydrated through graded alcohols. Endogenous per-
oxidase activity was blocked by 3% hydrogen peroxide in
methanol (10 minutes) and washed in phosphate-buffered saline.
After incubation with 10% nonimmune goat serum (10 minutes)
to block nonspecific binding, slides were incubated with the pri-
mary antibody for 1 hour in a moist chamber. Sections were
washed in phosphate-buffered saline and incubated with biotiny-
lated antimouse IgG (10 minutes) followed by incubation with
avidin-biotin complex and horseradish peroxidase reagents (10
minutes) at room temperature. Visualization with the AEC kit
(Zymed, San Francisco, CA) was followed by counterstaining
with Mayer hematoxylin.
PCR Studies
DNA Extraction
Sections, 5 m thick, were prepared under sterile condi-
tions. DNA was extracted by Proteinase K digestion at 55C
overnight, followed by chloroform-phenol extraction using
standard protocols.
Detection of T-Cell Receptor and Immunoglobulin Gene
Rearrangement
Approximately 1 to 2 g of extracted genomic DNA was
used as a template for PCR with consensus primers for the
variable (V) and joining (J) regions of T-cell receptor (TCR)
chain genes and the immunoglobulin heavy chain (IgH) gene
as previously described.
14
Automated High-Resolution PCR Fragment Analysis
(Spectratyping)
Spectratyping allows analysis of all V and J regions of the
TCR chain gene using 4 sets of consensus primers specific for
the V regions of the TCR chain gene and primers specific for
the J region. Spectratyping analysis of the T-cell rearrangement
is an accurate, essential tool for detecting clonality and has
been found to be superior to the conventional PCR reaction.
The primers were labeled at the 5' end with 5-carboxy-
fluorescein (FAM). After amplification, the labeled PCR prod-
ucts were separated by using an automated sequencing system
(ABI 310; Applied Biosystems, Weiterstadt, Germany).
During electrophoresis, the capillary was scanned and the
intensity of the fluorescent signals analyzed using Genescan
Software ABI 672 (Applied Biosystems). The electrophoretic
profile of PCR products demonstrates the presence of mono-
clonal, oligoclonal, or polyclonal populations according to the
number and distribution of signal peaks. Polyclonality is rep-
resented by a Gaussian distribution of the PCR products,
oligoclonality corresponds to a skewed TCR repertoire as
visualized by spectratyping, and monoclonality to a single
peak. In each case, the TCR repertoire was tested by 4 PCRs,
and duplicate runs were performed to confirm reproducibility.
Results
A search of the files between 2000 and 2004 retrieved 12
cases of TUGSE. The clinical data are shown in Table 2.
Most patients were older than 50 years (mean, 49.2 years),
with an equal sex distribution. Patients were otherwise healthy
without reported skin lesions.
Table 1
Monoclonal Antibodies Used in the Study
Antigen Target Source
CD30 Activation/early differentiation antigen DAKO, Carpinteria, CA; mouse antihuman CD30
ALK Anaplastic lymphoma kinase Zymed, San Francisco, CA; rabbit, polyclonal anti-ALK
TIA-1 T-cell intracytoplasmic antigen Biocare Medical, Concord, CA; monoclonal antihuman TIA
CD4 T-cell subset (helper) Zymed; mouse antihuman T-cell
CD8 T-cell subset (cytotoxic) Zymed; mouse anti-CD8
CD3 T lymphocytes DAKO; mouse polyclonal antihuman T-cell
CD20 B lymphocytes DAKO; mouse antihuman B-cell clone L26
von Willebrand factor Endothelial cells Zymed; mouse antihuman von Willebrand factor clone F8/86
CD68 Macrophages, monocytes DAKO; mouse antihuman macrophage CD8 clone PG-MA
Ki-67 Proliferation marker DAKO; mouse antihuman clone MIB-1
524 Am J Clin Pathol 2006;126:522-529
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Hirshberg et al / TRAUMATIC ULCERATIVE GRANULOMA
In all patients, there was only a single lesion at the time
of examination. The tongue was involved in 7 cases and the
vestibule, buccal mucosa, and floor of the mouth in the
remaining 5 cases. The lesions manifested mostly as chronic
ulceration with rolled-up margins, usually associated with
mild pain. In case 1, the lesion appeared as an exophytic mass
in proximity to the margin of a denture (epulis fissuratum).
Information on duration was limited to general estimations by
patients and varied from several days to 1 year.
Local trauma could be considered an etiologic factor in 4
cases, 2 resulting from a sharp tooth cusp and 1 from an ill-fit-
ting denture; 1 developed following a biopsy for leukoplakia
several months earlier. In the remaining 8 cases, local trauma
had not been identified. Healing was uneventful in all cases,
without recurrences, following excisional or incisional biopsy.
Histopathologic Findings
All cases showed ulcerated mucosa with a dense cellular
infiltrate focally involving the epithelium, extending into the
deeper underlying soft tissues and between the muscle fibers
Image 1. The infiltrate was composed primarily of small,
round lymphocytes, granulocytes, and abundant eosinophils
Image 2. In 7 cases, large atypical cells could be identified in
clusters or scattered as single cells within the inflammatory
infiltrate; the large cells had irregular nuclear contours, fine
chromatin, small nucleoli, and abundant cytoplasm Image 3.
In case 2, mitotic figures were observed in several of the large
cells Image 4. Proliferating endothelial cells and blood ves-
sels were distributed throughout the lesion. The diagnostic cri-
teria for TUGSE were met in all cases. However, in case 2,
malignant T-cell lymphoma had been suspected because of the
Table 2
Clinical Data for 12 Patients With Traumatic Ulcerative Granuloma With Stromal Eosinophilia
Case No./ Size Recurrence/
Sex/Age (y) Location Duration (mm) Treatment Follow-up (y) Trauma
1/F/51 Anterior maxillary vestibule 1 y 12 Excision No/1.5 Trauma from denture
2/M/55 Tongue, dorsal Unknown 10 Excision No/2.5 None
3/F/72 Mandibular vestibule Few days 8 Excision No/4 None
4/F/67 Tongue, ventral 1 mo 5 Excision No/3 None
5/M/14 Buccal mucosa 2 mo 3 Excision No/3.5 Trauma, sharp tooth cusp
6/M/87 Floor of mouth 3-4 wk 12 Excision No/3.5 None
7/M/57 Tongue, posterior lateral Several months 13 Excision No/3 Trauma, sharp tooth cusp
8/M/52 Tongue, anterior lateral Unknown 4 Excision No/3 Following incisional biopsy for leukoplakia
9/F/36 Mandibular vestibule Several months 12 Excision No/4.5 None
10/F/44 Tongue, middle lateral Several months 15 Excision No/4 None
11/F/34 Tongue, middle lateral Several months 5 Excision No/2 None
12/M/21 Tongue, middle lateral Unknown 10 Excision No/1.5 None
Image 1 Traumatic ulcerative granuloma with stromal
eosinophilia. Low-power image showing ulceration with a
dense inflammatory infiltrate extending deep into the muscle
of the tongue (H&E, original magnification 40).
Image 2 Traumatic ulcerative granuloma with stromal
eosinophilia. High-power image showing the inflammatory
infiltrate composed mainly of small, round lymphocytes,
granulocytes, and abundant eosinophils (H&E, original
magnification 200).
Am J Clin Pathol 2006;126:522-529 525
525 DOI: 10.1309/AFHA406GBT0N2Y64 525
American Society for Clinical Pathology
Hematopathology / ORIGINAL ARTICLE
presence of a subpopulation of large, atypical monocytoid
cells with abundant mitotic figures that focally infiltrated
blood vessel walls.
Immunohistochemical Findings
Table 3 summarizes the immunohistochemical
results. The lymphocytic infiltrate was composed primarily
of a mixture of B and T lymphocytes. The T-lymphocyte
population usually showed an approximately equal distri-
bution of helper and cytotoxic cells. Prominent focal aggre-
gates of T lymphocytes (CD3+ and T-cell intracytoplasmic
antigen 1+) were noticed in most cases, whereas in case 1,
these cells composed the majority of the infiltrate. CD68+
cells (macrophages) intermixed with the inflammatory
infiltrate were found in most cases, and von Willebrand
factor was positive in blood vessel walls. Between 10% and
50% of all lymphocytes expressed the proliferation marker
Ki-67 in small and large cells Image 5.
Small clusters of CD30+ cells were found in 1 case
(case 2). These were composed of large, atypical cells found
in small aggregates infiltrating into the underlying muscle
Image 6. In 4 other cases, single CD30+ cells were found
scattered within the lymphoid infiltrate. Anaplastic lym-
phoma kinase was negative in all cases examined.
Large cells were found in 7 cases, the majority were
positive for T-cell markers, and none were of B-cell origin.
Some but not all were CD30+. Other large cells reacted
with the macrophage marker CD68. Although large, plump
Table 3
Immunohistochemical Results in 12 Cases of Traumatic Ulcerative Granuloma With Stromal Eosinophilia
*
Large T-Cell Clonality
Case No. CD30 ALK TIA-1 CD4 CD8 CD3 CD20 vWF CD68 Ki-67 Cells Eosinophils Spectratyping
1 Positive (scattered) 0 2 1 1 2 1 1 1 2

+ 1-2 Oligoclonal
2 Positive (aggregates) 0 2 1 2 1 1 1 1 1-2

+ 1-2 Monoclonal
3 Positive (scattered) 0 3 2 1 1 1 1-2 1 1-2

+ 2 Oligoclonal
4 0 1 1-2 1 3 1 1 1 Polyclonal
5 0 2 1 2 1 2 1-2 1 2 1-2 Polyclonal
6 0 3 1 1 1 1 2 1 1 1-2 Polyclonal
7 Positive (scattered) 0 1 1-2 1 1 1 1-2 1 1-2

+ 1 Oligoclonal
8 Positive (scattered) 0 3 2 1 2 1 1 0-1 1-2

+ 1 Polyclonal
9 0 2 0-1 0-1 1 0-1 0-1 0-1 1

+ 1 Oligoclonal
10 0 2 2 2 1 1-3 1 0-1 1

+ 1 Oligoclonal
11 0 2 1 1 1 1 1 1 1 1-2 Polyclonal
12 0 3 2 1 1 1 1 0 1 1-2 Polyclonal
ALK, anaplastic lymphoma kinase; TIA, T-cell intracytoplasmic antigen; vWF, von Willebrand factor; +, present; , negative or absent.
*
The semiquantitative scale was as follows: 0, none; 1, <25%; 2, 25%-50%; 3, 50%-75%; 4, >75%.

Positive in large and small cells.

Image 3 High-power image showing large cells with
irregular nuclear contours, fine chromatin, small nucleoli
(arrows) (H&E, original magnification 400).
Image 4 (Case 2) High-power image showing mitotic figures
in several of the large cells (arrows) (H&E, original
magnification 400).
526 Am J Clin Pathol 2006;126:522-529
526 DOI: 10.1309/AFHA406GBT0N2Y64
American Society for Clinical Pathology
Hirshberg et al / TRAUMATIC ULCERATIVE GRANULOMA
endothelial cells positive for von Willebrand factor were
found in the vessel walls, none of the scattered large cells
within the infiltrate reacted with this antibody.
Spectratyping Analysis
Six cases displayed a Gaussian distribution of the PCR
products indicating a polyclonal rearrangement of the TCR
genes Image 7. Skewing of the distribution, which indi-
cates oligoclonality, was found in 5 cases; in these cases,
there were between 2 and 6 dominant peaks per PCR prod-
uct (8-14 peaks per case for the 4 PCRs). Monoclonality
was observed in only 1 case (case 2), which corresponded to
the case microscopically suspected of being lymphoma
(Table 3). Analysis of the immunoglobulin gene rearrange-
ment disclosed a polyclonal distribution in all cases.
Follow-up
Recurrences or new lesions were not reported in any of
the cases within a follow-up period of 1.5 to 4.5 years. The
patient diagnosed with lymphoma also had no sign of local
recurrence or new lesions. Monoclonality for T-cell rearrange-
ment was not found in bone marrow aspirate and biopsy spec-
imens or in his peripheral blood specimen. The patient is still
being monitored closely more than 2 years after removal of
the tongue lesion, with long-term follow-up planned.
Discussion
TUGSE is an obscure lesion that affects the oral mucosa.
The most frequent clinical manifestation is that of an ulcer,
Image 5 K-67labeled section showing labeling of about
50% of the cells (original magnification 200).
Image 6 CD30-labeled section showing clusters of CD30+
cells extending into the underlying muscle (original
magnification 400).
560
420
280
140
0
1,600
1,200
800
400
0
240 280
400
300
200
100
0
A C
B
Image 7 A, Gaussian distribution of polymerase chain
reaction (PCR) products of rearranged T-cell receptor genes
indicates the presence of a polyclonal T-cell population. B,
Skewed distribution of the PCR products indicates the
presence of an oligoclonal T-cell population. C, A dominant
peak of PCR products indicating the presence of a
monoclonal T-cell population.
Am J Clin Pathol 2006;126:522-529 527
527 DOI: 10.1309/AFHA406GBT0N2Y64 527
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Hematopathology / ORIGINAL ARTICLE
often with rolled borders, which mimics squamous cell carci-
noma. The duration of TUGSE varies, ranging from several
weeks to several months and even up to 1 year (1 case in the
present series).
Microscopically, TUGSE is characterized by a dense
polymorphic inflammatory infiltrate extending into the under-
lying muscle. The dominant cell types in the inflammatory
infiltrate are small lymphocytes, with abundant eosinophils. In
the present study, B and T lymphocytes were found in all
cases. Focal aggregates of T lymphocytes were common in
most cases; in case 1, T cells dominated for an unclear reason.
The presence of eosinophils is not completely understood
because most traumatic oral ulcers are devoid of eosinophils. It
has been suggested that eosinophils represent a tissue reaction
to some unknown antigen introduced via mucosal breakdown
following trauma.
2
Mucosal degeneration so characteristic of
TUGSE may be attributed to proliferation of cytotoxic T cells
or toxic products released by degranulating eosinophils.
Aggregates of T-cell intracytoplasmic antigen 1+ cells, a
marker of cytolytic T cells, were found in large quantities in
all cases in the present study, supporting the role of cytotoxic
T cells in the pathogenesis of TUGSE.
Eosinophils have been found to generate a wide spectrum
of inflammatory and regulatory cytokines
15-19
; some of these,
such as tumor necrosis factor, can enhance tissue damage. In
most of their TUGSE cases, Elovic et al
20
showed a lack of
significant synthesis of transforming growth factor by
eosinophils, which can explain the delayed healing character-
istic of TUGSE.
The presence of large, atypical mononuclear cells is
another microscopic feature of TUGSE present in most cases
(58% in the present study). The origin of these large cells has
been a matter of debate. Regezi et al,
8
in a study of 8 cases,
detected the macrophage marker CD68 or the dendrocyte
marker factor XIIIa. El-Mofty et al,
7
however, in a series of 38
cases, found that the atypical large cells were positive only for
vimentin, suggesting that they represent myofibroblasts.
It has been suggested that TUGSE may be a CD30+ lym-
phoproliferative disorder.
12,13
CD30 is a transmembrane glyco-
protein with an extracellular domain homologous to the tumor
necrosis factor/nerve growth factor receptor superfamily, orig-
inally described as a surface molecule recognized by the Ki-1
monoclonal antibody on Reed-Sternberg cells.
21
CD30 is com-
monly expressed on activated B and T cells. Certain lympho-
proliferative disorders express the CD30 antigen. The spectrum
of CD30+ cutaneous lymphoproliferative disorders includes
lymphomatoid papulosis, primary cutaneous anaplastic large
cell lymphoma, and borderline CD30 lesions.
22,23
The
involvement of the oral cavity with lymphoproliferative disor-
ders, although rare, has been reported,
24-26
but the literature is
somewhat confusing, and definite comparison is difficult
because CD30 was not evaluated in these studies.
Ficarra et al
12
were the first to report a case in which
CD30+ cells were found in an ulcerated lesion histologically
resembling TUGSE. The patient had multiple episodes of
recurrent, self-healing eosinophilic ulcers in the oral mucosa.
It was suggested that TUGSE of the oral mucosa may repre-
sent the oral counterpart of cutaneous CD30+ lymphoprolifer-
ative disorder. Alobeid et al
13
recently described 3 patients
with oral TUGSE containing CD30+ atypical cells in which T-
cell clonality was demonstrated by using PCR analysis of the
TCR chain gene. In 1 case, the lesion healed completely fol-
lowing incisional biopsy; in the other 2 cases, additional self-
healing oral and extraoral lesions developed. Contrary to the
findings of Ficarra et al,
12
Alobeid et al
13
believed that the
lesions they reported represented a subset of cases of TUGSE
that share common features with primary cutaneous CD30+
lymphoproliferative disorders.
CD30 expression also has been found in nonneoplastic
disorders, such as atopic dermatitis,
27
drug reactions,
28,29
sca-
bies,
30
and molluscum contagiosum.
31
Cepeda et al
32
demon-
strated the presence of CD30+ lymphoid cells in 70% of a
group of common nonneoplastic cutaneous conditions rich in
neutrophils and eosinophils. All cases studied were polyclo-
nal for TCR rearrangements. Of the 28 cases, 5 cases were
insect bites, 4 of which contained CD30+ cells. Their study
indicates that CD30+ cells are a component of a reactive
rather than a neoplastic process. In the present study, clusters
of CD30+ cells were identified in 1 case and scattered, single
CD30+ cells were found in 4 other cases. In the absence of
additional clinical and histologic support, a diagnosis of lym-
phoproliferative disorder cannot be established. The fact that
anaplastic lymphoma kinase, a marker associated with large
cell CD30+ lymphoma, was negative in all cases in the pres-
ent study further supports the reactive nature of TUGSE.
The presence of a dense, lymphoid infiltrate in a lesion
may raise suspicions of lymphoid malignancy. Several benign
reactive lesions containing a significant lymphoid component
that may demonstrate histologic atypia should be considered
in the differential diagnosis, such as angiolymphoid hyperpla-
sia with eosinophilia, atypical histiocytic granuloma, and lym-
phomatoid papulosis.
26,33-38
A careful search for other charac-
teristics of malignant lymphoma should always be performed
to aid in differentiating true malignant lymphoma from reac-
tive benign lesions, such as abundant atypical cells infiltrate,
significant mitotic activity, and infiltration into blood vessel
walls. In some cases, however, the diagnosis may be difficult
to reach with confidence on the basis of histologic and
immunohistochemical findings alone. Low-grade lymphoma,
for example, may only be recognized retrospectively, when
lesions recur several times, spread to other areas, or develop
more pronounced malignant features microscopically.
In the present study, case 2, in addition to features of
TUGSE, fulfilled many histologic criteria for lymphoma.
528 Am J Clin Pathol 2006;126:522-529
528 DOI: 10.1309/AFHA406GBT0N2Y64
American Society for Clinical Pathology
Hirshberg et al / TRAUMATIC ULCERATIVE GRANULOMA
Spectratyping analysis of this case demonstrated clonal
rearrangement of TCR genes, supporting the diagnosis of T-
cell lymphoma. The lesion had healed nicely by the time the
molecular workup was completed, and no recurrence or
lesions at other organs were found in more than 2 years of fol-
low-up. Detection of a dominant clone of a T-cell population
as a single criterion in a lymphoproliferative process is insuf-
ficient to diagnose a T-cell lymphoma. Because spontaneous
regression of T-cell lymphoma is a recognized phenomenon,
39
the question of the true nature of the lesion in this particular
case cannot be resolved. Nevertheless, in the presence of mono-
clonality, a lymphoma workup should always be undertaken,
and lifelong follow-up is mandatory. For the other cases ana-
lyzed in the present series, polyclonality was present in 6
cases and oligoclonality in 5 cases, an indication of their reac-
tive nature. Based on the present study and information in the
literature, TUGSE is self-limiting and rarely recurs. In the
absence of alarming histologic findings, a follow-up period of
1 or 2 years seems adequate.
In the present study, the phenotypic and genotypic profile
of TUGSE was characterized. It can be suggested that most
cases of TUGSE are reactive; some, however, may harbor a
dominant clonal T-cell population. Atypical histologic find-
ings in addition to the presence of monoclonality can serve as
a warning sign for a malignant lymphoid proliferation. The
question of whether monoclonality indicates a true T-cell lym-
phoma of low-grade malignancy or a variant of a reactive lym-
phoproliferative process to some unknown stimulus has not
been resolved.
From the
1
Department of Oral Pathology and Oral Medicine,
Maurice and Gabriela Goldschleger School of Dental Medicine,
Tel Aviv University, Tel Aviv, Israel;
2
Laboratory of Hematology
and Molecular Biology and
3
Department of Oral and
Maxillofacial Surgery, Sheba Medical Center, Tel-Hashomer,
Israel;
4
Department of Hematology and Bone Marrow
Transplantation, Rambam Medical Center and Bruce Rappaport
Faculty of Medicine, Haifa, Israel; and
5
Institute of Pathology,
Rabin Medical Center, Bellinson Campus, Petah-Tiqva, Israel.
Address reprint requests to Dr Hirshberg: Dept of Oral
Pathology and Oral Medicine, Maurice and Gabriela
Goldschleger School of Dental Medicine, Tel Aviv University, Tel
Aviv, Israel.
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