We have described a rare case of primary GEJ HL. Lymphoma is foremost a malignancy of lymph nodes with over 66% of NHLs and almost all HLs presenting as a lymphadenopathy (6
). The GI tract is the most common site for extranodal lymphoma, especially in the stomach (6
). Criteria for the diagnosis of primary GI lymphoma were established by Dawson et al (8
) in 1961 and are still in use (1
). Criteria included the location of the bulk of the lymphoma in the digestive tract, an absence of superficial and mediastinal lymphadenopathy, an absence of organomegaly, no bone marrow involvement and a normal peripheral complete blood count.
Gastric HL is extremely rare, accounting for fewer than 1% of all gastric primary lymphoma (1
). The malignancy has a slight male predominance ratio of 1.2:1, a peak incidence in the fifth to sixth decades and may have a propensity for the antrum and pylorus (1
). Presenting symptoms include: upper abdominal pain, nausea, vomiting, GI bleeding and weight loss (3
). Our patient satisfied the criteria for a GI primary HL, albeit symptoms of dysphagia are not typical for gastric HL.
Because primary gastric HL is a remote entity, the diagnosis requires validation through ancillary investigation (1
). Historically, an accurate diagnosis of gastric HL is not established on mucosal biopsies procured by endoscopy (3
). Ogawa et al (3
) reported that of the 100 gastric HL cases between 1924 and 1993 (before surgical resection), accurate diagnoses were established in only three cases. There was no speculation as to why preoperative diagnostic material was difficult to ascertain. Despite having original positive mucosal biopsy material in our case, we requested a second endoscopic biopsy for ancillary investigations that confirmed the diagnosis of HL. Certainly, technological advances in imaging methodologies, endoscopy and ancillary testing should accommodate successful tumour sampling by minimally invasive techniques.
HL of the esophagus is usually a contiguous extension of an adjacent lymph node or gastric primary malignancy (5
). Primary esophagus HL is an extremely rare lesion with a propensity for the mid- or proximal one-third (5
). A variety of clinical presentations include odynophagia/dysphagia, weight loss, epigastric pain, fullness/bloating, anorexia, nonspecific ‘type B’ symptoms, aneurysmal dilation of the esophagus and tracheoesophageal fistula (5
). When located in the lower esophagus, 30% of HLs are complicated by stricture formation (5
). Our patient’s symptoms more accurately reflected those of a cardia or lower esophageal primary malignancy. The radiological finding of lymphadenopathy in neighbouring lymph nodes is compatible with the expected contiguous dissemination of an HL.
The classic endoscopic appearance of esophageal HL is an ulcerated mass, often indistinguishable from a carcinoma (5
). Despite the obvious mucosal embarrassment, repeat endoscopic biopsy, open biopsy or surgical resection is often required to establish a diagnosis (5
). It has been speculated that endoscopy may be an inadequate procedure for the assessment of HL because the tumour may have an origin deep in the wall of the viscera (5
). However, because GI lymphoid tissue is almost exclusive to the mucosa and submucosa, primary lymphoma should be amenable to transmucosal biopsy procedures. A deep mural origin of HL and/or nondiagnostic mucosal biopsy material would confer that primary disease is actually extramural and/or nodal. If a diagnostic mucosal biopsy were a required criterion for confirming HL of GI origin, disease prevalence may be reduced to extremely rare anecdotal cases.
The RS cell is pathognomonic of HL, regardless of tumour location (2
). These large cells can have various morphologies including uni- or multinucleation, but a prominent eosinophilic inclusion-like nucleolus is standard (6
). Cells with similar morphology can be present in a number of processes so that the differential diagnosis of HL includes: ALCL, adult T cell lymphoma, malignant histiocytosis, poorly differentiated carcinoma, sarcoma and melanoma (1
). Histology and molecular biology analysis are essential for establishing a definitive diagnosis. PAX5 is a pan-B cell antibody that facilitates the exclusion of other lymphoproliferative disorders from HL (12
). Specifically, ALCL and other T cell lymphomas are uniformly negative for PAX5, while 97% of HL RS cells are weakly positive (12
). Only 4% of DLBL have a weak PAX5 staining pattern because most are strongly positive (12
). MUM1 stains 100% of classic HL RS cells and is much less sensitive for DLBL (13
). One caveat is that large atypical cells of lymphocyte-predominant HL have been reported to be MUM1-negative (13
). Because mucosal biopsy material may lack architectural landmarks typical of HL, confirmation of the diagnosis mandates the use of highly sensitive IHC antibodies for RS cells such as PAX5 and MUM1 to exclude T cell lymphomas and DLBL, respectively.
Contrary to existing literature, we advocate that the transmucosal biopsy should provide diagnostic material for a GEJ HL. Obvious neoplasm in a mucosal biopsy must be a criterion for confirming HL of viscera origin because it detracts from the possibility that the bulk of the disease is actually extramural/in a lymph node. Allocating fresh tissue for the multitude of essential ancillary studies may be jeopardized when HL is not suspected clinically. Thus, repeat endoscopy may not be avoidable in the assessment of such a neoplasm. Architectural features of HL may be limited on mucosal biopsy material and, thus, highly sensitive IHC antibodies such as PAX5 and MUM1 must be used to confirm this remote scenario that could manifest as a gastric or esophageal ulcerating mass.