Here, we report a case of HS with an unknown primary lesion and a unique clinical course. A literature search revealed no previous reports of HS with gastrointestinal ischemia caused by a tumor embolism. Tumor embolism is common in lung cancer with invasion into the pulmonary veins or the left atrium because tumor fragments resulting from direct invasion of the tumor into the bloodstream can cause occlusion [11,12,13]. Systemic HS in this case suggests that tumor fragments invaded through vulnerable blood vessels. The most frequent clinical presentation is acute cerebral stroke, followed by acute myocardial infarction and acute lower limb ischemia [12]. Ischemic enteritis due to tumor embolism is rare but has been reported in cases of lung [11] and rectal [14] cancer.

The symptoms of HS, when present, are nonspecific, including fever, fatigue, night sweats, and weight loss similar to other blood lymphoid tumors. Some previous reports revealed that extranodal multisystemic HS with gastrointestinal lesions might cause intestinal obstruction [15] and perforation [16]. The patient in this case exhibited few symptoms until he was rushed to the emergency department. No findings suggesting tumor embolism were observed on the preoperative contrast-enhanced CT though re-evaluating even after surgery.

Definitive diagnosis of HS was delayed because syphilis was a comorbidity in this case. Multiple nodules were initially identified as systemic manifestations of syphilis based on the laboratory findings, and antibiotics were administered as diagnostic treatment because no other suspicious diseases were evident at the initial treatment. Histological examination is beneficial in differentiating HS from syphilis, so we should have performed multiple pathological examinations of subcutaneous nodules earlier until we confirmed a definitive diagnosis. During laparotomy, necrosis and normal small intestine were distinguished by color tone and arterial pulsation. ICG fluorescence imaging was not used because it is limited to use overtime at our hospital and the boundaries were clear. Resection of transverse colon cancer was not performed because multiple systemic nodules were suspected of malignant neoplasms intraoperatively, which defined the prognosis, but not transverse colon cancer.

When diagnosing HS, it is important to differentiate it from other hematopoietic tumors by immunostaining, following the World Health Organization classification [1]. Immunostaining showed that histiocytic markers, such as CD68, CD163, lysozymes, and S-100 protein, were generally positive, whereas dendritic cell markers, such as CD11c, CD21, and CD35, were negative [3, 9, 17], which is consistent with the findings of our case.

The differential diagnoses include undifferentiated sarcoma with reactive histiocytic proliferation and intravascular lymphoma. In this case, the histiocytes had cytologically malignant nuclei distinct from the bland and distinctive round nuclei, with a fine chromatin pattern found in most reactive histiocytic proliferations [3]. Moreover, this tumor predominantly manifested as an extravascular mass and tumor embolism. This differs from intravascular lymphoma, which predominantly accumulates and proliferates within blood vessels, and rarely forms an extravascular mass [18].

Chemotherapy was initiated for three reasons: First, the surgical intervention was performed immediately. Second, necrosis was localized within a part of the small intestine, and short bowel syndrome was avoided. Finally, the patient did not have ischemic necrosis in other organs due to arterial tumor embolism, cerebral stroke, or cardiac infarction.

Evidence regarding chemotherapy regimens is limited. A few cases of a good response to cyclophosphamide, doxorubicin, and vincristine therapy have been reported [19, 20]. However, the patient showed no obvious response to the chemotherapy. An accumulation of cases of HS and further studies on its treatment are required.