Sabato 27 ottobre 2012 - Pacini Editore

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Primary Hodgkin lymphoma of the anus:
case report and brief review of the literature
M.R. Ambrosio1 , B.J. Rocca1 , M.G. Mastrogiulio1 , A. Barone1 ,
G. De Falco1 , A. Costa2 , C. Bellan1 , S. Lazzi1 1 Department of Human Pathology and Oncology, Pathological Anatomy
Section, University of Siena, Italy; 2 Surgery Unit Valdichiana Hospital,
Montepulciano, Italy
Background. Primary anorectal lymphomas are very rare, with
a higher incidence in human immunodeficiency virus positive
(HIV+) patients. Most are high-grade B-cell non-Hodgkin
lymphomas (NHL) often associated with Epstein-Barr virus
(EBV). Anorectal Hodgkin lymphoma (HL) is rarer, accounting
for 20% of gastrointestinal HL in HIV+ individuals. In immunodeficiency
virus negative (HIV-) patients it is uncommon
and it has been reported particularly in the context of inflammatory
bowel disease (IBD). Primary HL of the anus has never
been previously described. We report the first case of anal HL
in a HIV- patient without IBD, highlighting the importance of
differential diagnosis with EBV-induced lymphoproliferative
disease (EBV-LPDs).
Materials and methods. a 83-year-old man presented to the
Surgery Unit of Valdichiana Hospital complaining of tenesmus
and mucous bloody diarrhea, that lasted for 1 month. Digital
rectal examination revealed a friable, hemorrhagic lesion located
in the anal canal. The rest of the physical examination
was unremarkable. No superficial lymphadenopathy or hepatomegaly
were identified. A rectoscopy showed an ulcerative
lesion of the anal canal. The ulcer extended through the entire
anal wall, the margins were protruding. A whole body computed
tomography (CT) scan showed an ill-defined tumor, 40x15
mm, extending through the entire right wall of the anal canal.
Mild (10 mm) regional lymphadenopathy was also identified.
No periaortic lymphadenopathy or lesions in the liver, spleen
and lungs were detected. A complete blood count was normal.
The clinical differential diagnosis included: localized anal
carcinoma, anal isolated ulcer, Crohn disease. Tissue samples
were taken; formalin-fixed, paraffin-embedded tissue blocks
were cut and stained for hematoxylin and eosin. The following
antibodies were checked: CD45, CD20, CD3, CD30, CD15,
OCT-2, BOB-1, LMP-1, Cytomegalovirus (CMV). In situ hybridization
analysis for EBV small-encoded RNA (EBER) was
also performed as well as Polymerase chain reaction (PCR) for
Human Papillomavirus (HPV).
Results. the surgical specimens consisted of 5 friable brownish
fragments ranging between 10 and 40 mm in maximum diameter.
Histologically, all the fragments showed similar morphologic
features: not well-circumscribed ulcerated mucosal lesions were
associated to a polymorphous infiltrate with a mixture of lymphocytes,
plasma cells, histiocytes, immunoblasts and scattered
eosinophils. Reed-Sternberg (RS) and Hodgkin cells (HC) were
present in variable number. The adjacent squamous epithelium
showed reactive nuclear atypia. The neoplastic cells were positive
for CD30 and CD15 with a paranuclear and membranous
pattern of staining, and for LMP-1; they were negative for CD45,
CD20, CD3, Oct-2, Bob-1. Immunohistochemistry for CMV was
CONGRESSO aNNualE di aNatOmia patOlOGiCa SiapEC – iap • fiRENzE, 25-27 OttOBRE 2012
negative. In situ hybridization analysis for EBER was positive
whereas PCR for HPV was negative. The histological, immunohistochemical
and in situ hybridization findings supported the
diagnosis of classical HL. A post-diagnosis 2-fluoro-2-deoxy-Dglucose
(FDG)-PET/CT showed an area of abnormally high FDG
uptake in the anal canal and in the left inguinal lymph nodes.
The patient received pelvic irradiation with 40 Gy. At present
(6 months after the initial diagnosis) the patient is alive without
any clinical, endoscopic and radiologic signs of local relapse or
active HL.
Conclusions. This is the first case of an isolated anal localization
of HL in a HIV- patient. In our review of the literature, we
have identified only two cases of ano-rectal HL but no cases
exclusively located in the anus. In both cases the patients were
male of 33-year old, HIV+. The lack of complete clinical,
and immunohistochemical data as well as EBV status in one
of the cases calls into question the diagnosis of primary HL.
Diagnosis of extranodal HL can be challenging because of the
polymorphic nature of the cellular infiltrate, the paucity of the
malignant cells and the fact that normal anorectal mucosa is devoid
of lymphoid tissue. However, lymphoid infiltration can be
induced in the context of chronic inflammation or immune deficiency.
Differential diagnosis with atypical lymphoid hyperplasia,
particularly associated with virus, as such as EBV, may
be difficult and a combination of clinical, morphologic and
immunophenotypic parameters is useful in reaching the correct
diagnosis. EBV-LPDs are lymphoid proliferations that arise as
a result of immunodeficiency due to a primary immunodeficiency
or immunoregulatory disorder (i.e. HIV infection, posttransplant
setting, iatrogenic cause such as methotrexate and
TNF-ɑ antagonists and ageing). In physiologic circumstances
the inherent propensity of EBV to induce B-cell proliferation
is counterbalanced by complex immunologic interactions that
maintain the overall number of EBV-infected B cells in the
body at a very low level. Immunosuppression affects various
aspects of immune homeostasis and surveillance, thus permitting
the emergence of EBV-induced EBV-LPDs. Specifically,
in the elderly the T-cell response seems most profoundly affected,
with the accumulation of clonal CD8 positive T-cells
with mature, memory cell phenotypes but diminished functionality,
owing to a markedly restricted epitope specific repertoire
and a 100-fold decrease of T-cell specificities. In EBV-LPDs
the lesion are superficial and well-demarcated with a rim of
small lymphocytes, and plasmacytoid apoptotic cells which are
considered a hallmark of retained normal control mechanisms.
Moreover, RS and H-like cells showed wide range in size;
they are CD45 and Oct-2 positive, with variable expression
of Bob-1 and CD15. On the contrary in HL, RS and HC, as
in our case, are CD30 and CD15 positive and CD45 negative
with lack of expression of Oct-2 and Bob-1. In summary, we
report an unusual case of HL arising in the anus of 83-year-old
man in which only the association between clinical, histological
and radiologic findings led us to a correct diagnosis. The
importance of distinguish HL from EBV-LPDs, particularly in
organs not common affected by HL, is stressed and the need
for caution when considering such a diagnosis in HIV- patients
with no history of IBD is underlined.
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