The molecular marker INI-1 loss, while characteristic of epithelioid sarcoma, is not pathognomonic. Other malignancies, like epithelioid angiosarcoma, can also have this finding. Clinicians must integrate molecular data with the patient's age and clinical presentation to confirm the diagnosis, sometimes requiring a re-biopsy in atypical cases.
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Relying solely on Next-Generation Sequencing (NGS) is insufficient for HER2 testing in biliary tract cancers. Data shows NGS misses up to 15% of patients with HER2 overexpression detected by immunohistochemistry (IHC). Performing both tests is essential to avoid denying patients effective targeted therapies.
A patient with a history of DLBCL presenting with a relapse confined to the skin without lymphadenopathy should raise suspicion. This presentation "smells a lot like Marginal Zone Lymphoma," a less aggressive cancer that may be managed differently, highlighting the need to question histology in atypical relapses.
There's a growing recognition that the molecular profile of a primary tumor can differ significantly from its metastases. To guide treatment more accurately, the preferred practice is to biopsy an accessible metastatic lesion when possible, as this better reflects the biology of the active disease being treated.
While Next-Generation Sequencing (NGS) is routinely performed for young patients with epithelioid sarcoma, experienced clinicians note it seldom uncovers additional actionable mutations. The primary consistent finding is the SMARCB1 loss. This suggests that while NGS is part of comprehensive care, the likelihood of identifying other targetable pathways is currently very low.
The slow-growing nature of epithelioid sarcoma masses leads patients to dismiss them as benign issues like ganglion cysts. This patient-level delay is often compounded by diagnostic challenges at non-specialized centers, where the tumor's rarity can lead to misclassification as a 'poorly differentiated tumor,' delaying appropriate care.
A negative KIT mutation result from standard testing is often unreliable for ruling out systemic mastocytosis (SM). The low variant allele fraction requires highly sensitive assays like digital droplet PCR (sensitive to 0.03%) to avoid false negatives, which can prevent or delay correct diagnosis and treatment.
Clinicians ordering "NGS for lung" often misunderstand that Next-Generation Sequencing alone does not cover all actionable biomarkers, such as PD-L1 or HER2. This requires pathologists to interpret the clinician's intent and order a more comprehensive and appropriate test panel.
Experts express strong confidence in the effectiveness of radiation therapy for epithelioid sarcomas, noting the tumors are very sensitive to it. In difficult locally advanced cases, radiation is a key modality for gaining disease control and managing pain, with growing interest in combining it with immunotherapy to enhance its effects.
Frontline treatment selection hinges on histology. Non-epithelioid mesothelioma responds poorly to chemotherapy, making dual immunotherapy (Nivo/Ipi) the clear choice. For epithelioid cases, chemo-immunotherapy is a strong option, especially for symptomatic patients, due to its higher and faster response rate.
For very early-stage small cell lung cancer, surgical resection is an important and perhaps underutilized option. Beyond its therapeutic potential, surgery provides a definitive pathological diagnosis, which is crucial as some cases that appear to be small cell on biopsy may actually be other tumor types, like atypical carcinoid.
