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Molecular profiling of lung tumors is crucial for guiding targeted therapeutic strategies and identifying potential resistance mechanisms to specific therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). During this profiling, mutations with uncertain treatment implications can be identified. This case study represents a 69-year-old female with a co-occurring EGFR mutation profile that presents a unique therapeutic challenge. Tumor DNA was used for next-generation sequencing (NGS) of a custom 275 cancer-related QIAseq Human Comprehensive Cancer Panel (Qiagen). Next-generation RNA sequencing was performed using the Illumina TruSight panel. FISH analysis and PD-L1 22C3 immunohistochemical testing were also performed. Microscopic analysis revealed an invasive adenocarcinoma with papillary, acinar, and focal micropapillary features with a 6 mm invasive component. The final pathology stage was determined to be pT1aN0M0. NGS for DNA variant detection identified two mutations in EGFR, an EGFR G719A and EGFR L833_V834delinsFL with a variant allele frequency (VAF) of 22.2% and 21.1%, respectively. Targeted NGS RNA fusion analysis was also performed, which came back negative. PD-L1 22C3 immunohistochemical testing showed only 1% of the tumor cells expression. FISH analysis revealed one copy of MET and D7Z1 in 27% of cells, indicating an aneuploid neoplastic clone with monosomy 7. EGFR TKIs are universally accepted as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with a sensitizing EGFR mutation. While mutations such as G719A are sensitive to all generations of EGFR-TKI, the effects are unknown for rare compound mutations in EGFR, such as EGFR L833_V834delinsFL. There are no reports in the literature with any mention of an algorithm of treatment for such a case. The patient had two metachronous lung primary cancers resected in 2022 and 2024. Due to the complete surgical resection, the sensitivity of this mutation of TKIs could not be established. This unique mutation profile still remains of paramount importance to understand if the patient relapses or presents with a new tumor with the same genetic profile.

Molecular profiling of lung tumors is crucial for guiding targeted therapeutic strategies and identifying potential resistance mechanisms to specific therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). During this profiling, mutations with uncertain treatment implications can be identified. This case study represents a 69-year-old female with a co-occurring EGFR mutation profile that presents a unique therapeutic challenge. Tumor DNA was used for next-generation sequencing (NGS) of a custom 275 cancer-related QIAseq Human Comprehensive Cancer Panel (Qiagen). Next-generation RNA sequencing was performed using the Illumina TruSight panel. FISH analysis and PD-L1 22C3 immunohistochemical testing were also performed. Microscopic analysis revealed an invasive adenocarcinoma with papillary, acinar, and focal micropapillary features with a 6 mm invasive component. The final pathology stage was determined to be pT1aN0M0. NGS for DNA variant detection identified two mutations in EGFR, an EGFR G719A and EGFR L833_(V)834delinsFL with a variant allele frequency (VAF) of 22.2% and 21.1%, respectively. Targeted NGS RNA fusion analysis was also performed, which came back negative. PD-L1 22C3 immunohistochemical testing showed only 1% of the tumor cells expression. FISH analysis revealed one copy of MET and D7Z1 in 27% of cells, indicating an aneuploid neoplastic clone with monosomy 7. EGFR TKIs are universally accepted as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with a sensitizing EGFR mutation. While mutations such as G719A are sensitive to all generations of EGFR-TKI, the effects are unknown for rare compound mutations in EGFR, such as EGFR L833_(V)834delinsFL. There are no reports in the literature with any mention of an algorithm of treatment for such a case. The patient had two metachronous lung primary cancers resected in 2022 and 2024. Due to the complete surgical resection, the sensitivity of this mutation of TKIs could not be established. This unique mutation profile still remains of paramount importance to understand if the patient relapses or presents with a new tumor with the same genetic profile.

Epstein-Barr virus (EBV) -associated follicular lymphoma is only rarely reported. Herein, we report the largest series analyzing prevalence and clinicopathologic characteristics of EBV-associated follicular lymphoma occurring in unselected cases. Out of 382 analyzed cases, 10 EBV-positive follicular lymphomas were identified (prevalence=2.6%, 95% confidence interval 1.3–4.0%). All EBV-positive follicular lymphomas showed EBV-encoded small RNA-positive lymphoma cells present in a follicular distribution. Of these, eight also had tissue available for testing of expression of latent membrane protein 1 (LMP1), out of which six (75%) were positive. There was a significant association with grades 3A-3B follicular lymphoma (P<0.0001) and CD30 expression (P=0.0002). EBV-positive follicular lymphomas were otherwise morphologically and immunophenotypically indistinguishable from EBV-negative cases of similar grade. Nine of the EBV-positive follicular lymphomas occurred in patients with no known history of immunosuppression, while one patient had a history of hydroxychloroquine administration for Sjögren’s syndrome. The mean age in the EBV-positive and -negative follicular lymphomas was 56 (range 31–83 years) and 49 years (range 25–92 years), respectively, with no statistically significant difference. Seven of the patients with EBV-positive follicular lymphoma had additional biopsies from different time points available for review, all of which showed progression of disease in the form of progression of tumor grade. Five of these progressed to diffuse large B-cell lymphoma, one of which had tissue available for testing and was EBV-positive. Our findings suggest that EBV infection may have a role in lymphomagenesis and/or disease progression in a subset of follicular lymphomas, thereby expanding the spectrum of recognized EBV-associated B-cell lymphomas.

Granulomatous inflammation has been reported to be associated with Hodgkin and non-Hodgkin lymphomas. Here, we report a case of recurrent diffuse large B-cell lymphoma (DLBCL) with extensive granulomatous inflammation that was initially misdiagnosed as granulomatous lymphadenitis. In 2019, a 75-year-old Caucasian male presented to our hospital with an enlarged right supraclavicular lymph node. He had a medical history of prostate cancer (in 2004), DLBCL (initially diagnosed in 2009), and rectal adenocarcinoma (in 2017), all of which responded well to treatment. In 2018, the patient had experienced right axillary adenopathy, weight loss, and intermittent night sweats. An excisional biopsy of a right axillary lymph node, performed at another institution, was diagnosed as granulomatous lymphadenitis. In 2019, at our hospital, an excisional biopsy of a right supraclavicular lymph node showed DLBCL in a background of granulomatous inflammation. A review of the prior right axillary lymph node biopsy also showed DLBCL with a background of extensive granulomatous inflammation. Chemotherapy was initiated and the patient's follow-up showed a good response. We report this case to raise awareness that granulomatous inflammation may obscure the diagnosis of some neoplasms, such as DLBCL, which are less commonly known to have granulomatous inflammation. This may result in delayed treatment and may ultimately affect outcomes.Granulomatous inflammation has been reported to be associated with Hodgkin and non-Hodgkin lymphomas. Here, we report a case of recurrent diffuse large B-cell lymphoma (DLBCL) with extensive granulomatous inflammation that was initially misdiagnosed as granulomatous lymphadenitis. In 2019, a 75-year-old Caucasian male presented to our hospital with an enlarged right supraclavicular lymph node. He had a medical history of prostate cancer (in 2004), DLBCL (initially diagnosed in 2009), and rectal adenocarcinoma (in 2017), all of which responded well to treatment. In 2018, the patient had experienced right axillary adenopathy, weight loss, and intermittent night sweats. An excisional biopsy of a right axillary lymph node, performed at another institution, was diagnosed as granulomatous lymphadenitis. In 2019, at our hospital, an excisional biopsy of a right supraclavicular lymph node showed DLBCL in a background of granulomatous inflammation. A review of the prior right axillary lymph node biopsy also showed DLBCL with a background of extensive granulomatous inflammation. Chemotherapy was initiated and the patient's follow-up showed a good response. We report this case to raise awareness that granulomatous inflammation may obscure the diagnosis of some neoplasms, such as DLBCL, which are less commonly known to have granulomatous inflammation. This may result in delayed treatment and may ultimately affect outcomes.

Key Clinical Message Renal sarcoma is a rare and aggressive malignancy without proper guidelines for treatment. Due to the aggressiveness of this disease and the potential for recurrence, we believe that extensive surgical resection with healthy margins may be the best option to treat this condition during both initial resection and resection of the recurrent lesion. Clinical follow‐up is also important to monitor for tumor recurrence. Renal sarcoma is a rare and aggressive malignancy without proper guidelines for treatment. Due to the aggressiveness of this disease and the potential for recurrence, we believe that extensive surgical resection with healthy margins may be the best option to treat this condition during both initial resection and resection of the recurrent lesion. Clinical follow‐up is also important to monitor for tumor recurrence.

Primary intramedullary spinal cord lymphoma (PISCL) is rare and constitutes only 1% of central nervous system lymphomas. We report a case of PISCL in a 37-year-old man with advanced AIDS. To our knowledge, only 4 cases of PISCL in the setting of HIV/AIDS have been reported in the literature. Despite treatment, prognosis remains dismal.