Talimogene laherparepvec resulting in near-complete response in a patient with treatment-refractory Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous tumour of neuroendocrine cell origin, which can grow rapidly and metastasise early. Localised disease is treated with surgery and radiotherapy. Disease that reaches a more advanced stage can be treated with a variety of different treatment modalities including surgery, radiotherapy, chemotherapy, radionuclide therapy, immunotherapy, and intralesional therapy. We report a case of a patient who had exhausted all local and systemic treatment options and who subsequently had an exceptional response to intralesional injection of Talimogene laherparepvec (TVEC).

Three cases of BRAF-mutant melanoma with divergent differentiation masquerading as sarcoma.

Melanoma is an important cause of skin cancer related death throughout the world, particularly in Europe, the United States, and Australia. Rarely melanoma undergoes divergent differentiation to simulate the full morphologic and immunohistochemical features of other malignancies, notably sarcoma. However, such cases retain the molecular signatures of melanoma, including BRAF gene mutations. Gene mutation analysis of tumour DNA, now standard practice for all melanomas of stage III or above, may establish the diagnosis of melanoma in some advanced malignancies of unknown lineage. A prior history of melanoma or risk factors for melanoma may be the first clue that an advanced malignancy represents metastatic melanoma. Recognition of this presentation of melanoma can allow a patient to access well-tolerated life-prolonging therapies such as targeted therapy, inhibiting the BRAF/MEK pathway, and immune checkpoint inhibitor therapy.

Germline PALB2 Variants and PARP Inhibitors in Endometrial Cancer.

PARP inhibitors are orally administered antineoplastic agents that affect the homologous recombination (HR) repair pathway, and are approved by the FDA for the treatment of ovarian, breast, pancreatic, and prostate cancers. This report presents a case of recurrent endometrial carcinoma occurring in a woman with a germline pathogenic PALB2 whole-exon deletion. This uncommon finding in a patient with endometrial carcinoma provided the opportunity to use a management strategy of PARP inhibition with olaparib, resulting in a prolonged response to treatment; however, disease progression eventually occurred. Further studies are required to elucidate the mechanisms underlying resistance to PARP inhibition, and the potential future treatment options in this setting. Current recommendations for risk management of female carriers of PALB2 variants focus on breast and ovarian cancer risk. This case raises the additional question of a potential role for risk-reducing hysterectomy in female carriers of PALB2 variants.

Spatial transcriptomics in cancer research and potential clinical impact: a narrative review.

Spatial transcriptomics (ST) provides novel insights into the tumor microenvironment (TME). ST allows the quantification and illustration of gene expression profiles in the spatial context of tissues, including both the cancer cells and the microenvironment in which they are found. In cancer research, ST has already provided novel insights into cancer metastasis, prognosis, and immunotherapy responsiveness. The clinical precision oncology application of next-generation sequencing (NGS) and RNA profiling of tumors relies on bulk methods that lack spatial context. The ability to preserve spatial information is now possible, as it allows us to capture tumor heterogeneity and multifocality. In this narrative review, we summarize precision oncology, discuss tumor sequencing in the clinic, and review the available ST research methods, including seqFISH, MERFISH (Vizgen), CosMx SMI (NanoString), Xenium (10x), Visium (10x), Stereo-seq (STOmics), and GeoMx DSP (NanoString). We then review the current ST literature with a focus on solid tumors organized by tumor type. Finally, we conclude by addressing an important question: how will spatial transcriptomics ultimately help patients with cancer?