Gastric cancer or hodgkin lymphoma? Unraveling the diagnostic dilemma of primary gastric classical hodgkin lymphoma

INTRODUCTION

Lymphoma, which usually originates from the lymphatic system, can also involve the gastrointestinal (GI) tract when the disease is usually disseminated. Around 40% of the extra-nodal involvement of the lymphomas are from the GI tract^[1] with Non-hodgkin type (NHL), where the stomach is involved in the majority of patients, accounting for 60% of cases, followed by the small intestine and large intestine in 30% and 20% cases, respectively.^[2,3]

In contrast to NHL, hodgkin lymphoma (HL) usually involves cervical lymph nodes. The primary gastric classical hodgkin lymphomas (PGHL) without nodal involvement are rare.^[4] Because of the low suspicion of this type of cancer, along with the similarity in the clinical and radiological picture of gastric cancers, IHC plays a pivotal role in the confirmation of these cases. Only a few case series and reports have been published in the literature. Here, we describe a case of 45-year-old male patient with no palpable peripheral lymph nodes and mimicking gastric cancer who was surprisingly diagnosed as classical PGHL. The institutional review board approved this study and the patient’s consent was taken.

CASE REPORT

A 45-year-old man reported experiencing abdominal pain, nausea, and a significant weight loss of approximately 4–5 kg over the past 3 months. At presentation, he had no history of vomiting, hematemesis, or melena. He has no comorbidities such as diabetes mellitus, hypertension, or other significant family history of hereditary cancers.

The patient first visited a local hospital for acute abdominal pain and nausea and was on symptomatic treatment for a month. As his symptoms did not subside, he visited our hospital, one of the tertiary care centers, where he was advised for an ultrasound of the abdomen, which revealed circumferential asymmetrical wall thickening in the anthropologic region of the stomach measuring up to 14 mm with perigastric lymph nodes along the lesser and greater curvature. This again was confirmed by contrast-enhanced computed tomography of the abdomen.

He was then planned for upper GI endoscopy, where an ulceroproliferative growth was observed in the distal body, involving the lesser curvature and antrum, with the final diagnosis indicating carcinoma of the stomach. The biopsy from the growth revealed NHL and was advised for extended panel IHC. During this time, the patient underwent whole-body positron emission tomography-computed tomography because of lymphoma suspect, where mildly fluorodeoxyglucose (FDG)-avid irregular wall thickening is seen involving the body and antrum of the stomach with wall thickening of around 1.4 cm and standard uptake value max of 5.1 [Figure 1]. There were also a few inflammatory mildly FDG-avid inguinal lymph nodes.

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Figure 1:

Positron emission tomography-computed tomography ➜ FDG-avid irregular wall thickening involving the body and antrum of the stomach. FDG: Fluorodeoxyglucose.

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IHC report [Figure 2] surprisingly was compatible with HL, classical type mixed cellularity variant. The markers such as CD15, CD30, CD20, CD3, CD4, CD8, BCL2, and MUM1 were strongly positive and markers such as BCL6, EMA, CD5, CD23, CYCLIN D1, and ALK1 were negative. The leukocyte common antigen was negative in large cells but strongly diffusely positive in background B and T cells. The case was discussed in a multidisciplinary tumor board, following which the patient, diagnosed with PGHL (stage IE), was referred to a gastrosurgeon, where he was evaluated, and distal gastrectomy, Bill Roth II reconstruction, was performed. The histopathological specimen obtained from surgery confirmed lymphoma of the hodgkin variety arising from the stomach. Following surgery, he recovered quickly and was planned for standard Bleomycin-DacarbazineDoxorubicin-Vinblastine protocol. Post four rounds of chemotherapy, the patient had complete radiological as well as clinical response. He was on regular follow-up for 3-year post-completion of chemotherapy but was lost to follow-up thereafter.

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Figure 2:

Immunohistochemistry showing strong positivity of CD15, CD20, CD30, Ki67. 20X

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DISCUSSION

Lymphoma, usually a lymphatic system disease, can also be seen in the GI tract. Most lymphomas from the digestive system are of non-hodgkin variety,^[5] with the stomach being the most common involved organ and the esophagus the rarest.^[6]

Around 40% of extranodal lymphomas seen primarily in the GI tract are of NHL type and comprise 4% of all GI malignancies.^[7] The primary GI-HL is a rare entity. It comprises <1% of all the lymphomas in the GI tract.^[4,8] Only a few cases are documented in the literature, highlighting its rare incidence [Table 1].

Previous studies reported HL in 2–9% of cases; however, upon review with IHC, these cases were later reclassified as NHL.^[9] In our case, the patient initially presented with features suggestive of gastric cancer but was diagnosed as HL based on histopathology and IHC findings, thereby establishing the importance of IHC in diagnosing such peculiar cases without any dilemma.

Primary extranodal lymphomas are common in the stomach. Dawson et al.^[10] introduced diagnostic criteria for HL originating from the stomach in 1961, which even now is valid with little modifications and is used routinely in clinical practice. The following Table 2 summarizes the Dawson criteria for HL originating from the stomach:

It is difficult to diagnose gastric HL based on histopathology, as in our case, after doing the upper GI endoscopy, which was suggestive of carcinoma stomach based on ulcer proliferative growth at an antropyloric location. The histopathology report was suggestive of NHL and, certainly, after immunohistochemistry, confirmed to be lymphoma of the stomach of the hodgkin variety. Based on CD 30, the diagnosis of HL cannot be established as it can also be expressed in lymphomas such as peripheral T cell variant, anaplastic, and primary cutaneous lymph proliferative disorders. Hence, the extended panel of IHC is always needed to confirm the HL of the stomach and was done in our case to confirm the diagnosis.

PGHL treatment is not standardized because of the rare incidence. The literature suggests that the ideal approach of primary surgery followed by adjuvant chemotherapy to address systemic disease is the best treatment to date.^[18] Some case reports even suggest preoperative chemotherapy. In our case, the patient underwent distal gastrectomy, received four cycles of post-operative ABVD chemotherapy, and has been on follow-up for three years.

CONCLUSION

The HL of the stomach, clinical and radiological picture mimics the stomach cancer. Although the extranodal involvement of HL is rare, it should be one of the differentials so that it is not misdiagnosed. The role of extended panel IHC comes into the picture to confirm such rare cases. As per the available literature, primary surgery followed by adjuvant ABVD protocol is the best possible treatment to which patients respond exceptionally well, as was in our case.