Langerhans Cell Sarcoma (LCS) is an aggressive and extremely rare form of malignant histiocytosis, with a dismal prognosis.

A 62-year-old male with mild comorbidities (overweight, hypertension, type 2 DM and NAFLD) presented with chest and epigastric pain, without constitutional or neurological symptoms or skin changes. His physical examination was unremarkable, and initial evaluation only revealed mild elevation of liver enzymes and C-reactive protein. Abdominal MRI revealed several hepatic nodular lesions associated with large peritoneal nodules in the hepatic hilum, adjacent to the pancreas and along the curvatures of the body and gastric antrum. Upper gastrointestinal (GI) endoscopy showed a large subepithelial lesion with ulcerations in the gastric antrum. PET-CT pointed to hypermetabolic cervical (measuring up to 19 mm, SUVmax 29.8) and abdominal lymph nodes (measuring up to 53 x 32 mm, SUVmax 14), multiple hypodense hepatic lesions (measuring up to 22 mm, SUVmax 5.3), and an hypermetabolic lesion on the small curvature and gastric antrum (measuring 53 × 48 mm, SUVmax 23). There was no lung, bone or central nervous system disease. Incisional biopsies of stomach and liver lesions showed pleomorphic cells, some of them with evident nucleoli, atypia, frequent figures of mitosis and bizarre mitosis, and some with nuclei with fine chromatin, with identified clefts, both with surface expression of S-100, langerin (partial) and CD1a, that were designated as Langerhans Cell (LC) Neoplasia, most likely being LC Histiocytosis with atypical findings. This biopsy was reviewed by the Memorial Sloan-Kettering Cancer Center (MSKCC). BRAF V600E mutation was not identified. Patient received a first cycle of Cytarabine due to limited access to Cladribine, and then 2 cycles of Cladribine. PET-CT reevaluation after 3 cycles of chemotherapy showed involution of hepatic nodules and stability in most cervical lymph nodes, but volumetric and hypermetabolic increase in gastric lesions (63 ×62 mm, SUVmax 29,7) and in most abdominal lymph nodes. Upper GI endoscopy revealed bleeding in a large antral tumor. A new gastric biopsy showed atypical histiocytoid cells, some pleomorphic, with immunohistochemistry expression of CD68 (weak), S100m, CD1a, p53 (aberrant pattern) and Ki67 (75%), favoring transformation to LCS. Additional PD-L1 immunostain showed strong membranous staining, with CPS 37,5. A molecular analysis performed with the MSK-HEME-IMPACT multigene panel showed 22 mutations, including KRAS c.183A>C; p.(Gln61His) missense mutation, VAF 30,7%. In the meantime, the patient developed severe abdominal pain, GI bleeding and anemia. He received gastric external beam radiation therapy for symptom control, for a total dose of 3,000 cGy over 20 fractions. Considering the high PD-L1 tumor expression and cases previously reported, anti PD-L1 therapy with Pembrolizumab was initiated. So far, the patient has received three cycles of immunotherapy, with clinical and laboratory improvement. A PET-CT after 3 months of completion of radiotherapy will be performed to evaluate radiological response.

This case illustrates the aggressive course of LCS and the need for therapies beyond conventional chemotherapy, such as anti-PD1 therapy, to achieve disease control. Clinical trials for ultra-rare diseases are challenging to be conducted and discussion between centers may provide insightful treatment recommendations.