We present the case of a 70-year-old never-smoking female patient with epidermal growth factor receptor (EGFR) p.L858R-mutated metastatic non-small cell lung cancer (NSCLC). After three months of first-line treatment with erlotinib, progression occurred and platinum/pemetrexed was initiated, followed by a response for more than two years. After the progression, the molecular testing of a vertebral metastasis revealed a ROS proto-oncogene 1 (ROS1) translocation and a human epidermal growth factor receptor 2 (HER2) p.S310F mutation, in addition to the known EGFR p.L858R mutation. Crizotinib then led to a durable response of 17 months. The molecular retesting of the tumour cells obtained from the recurrent pleural effusion revealed the absence of the ROS1 translocation, whereas the EGFR and HER2 mutations were still present. Afatinib was added to the crizotinib, and the combination treatment resulted in another durable response of more than two years. The patient died more than 7 years after the initial diagnosis of metastatic NSCLC. This case demonstrates that the repeated molecular testing of metastatic NSCLC may identify new druggable genomic alterations that can impact the patient management and improve the patient outcome.

Lymphoblastic lymphoma (LBL) with an early T-cell precursor phenotype has only been rarely reported. Nijmegen breakage syndrome (NBS) is an inherited chromosomal instability disorder with known predisposition to malignancies that is very rare as well. We report a case of early T-precursor LBL (ETP-LBL) in a patient with NBS, a rare combination that has not been reported. We raise the question of whether a chromosomal instability disorder such as NBS increases the propensity for early T-precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL), given that ETP-ALL has been shown to have increased genomic instability compared to T-ALL.

This case report details a rare instance of a perforated jejunal gastrointestinal stromal tumor (GIST) in a 76-year-old female patient. The patient presented with acute abdominal pain and distension without any changes in bowel habits or episodes of nausea and vomiting. Initial diagnostics, including abdominal plain radiography and ultrasonography, were inconclusive; however, a computed tomography (CT) scan revealed pneumoperitoneum and an irregular fluid collection suggestive of small intestine perforations. Surgical intervention uncovered a 35 mm jejunal GIST with a 10 mm perforation. Histopathological examination confirmed a mixed cell type GIST with high malignancy potential, further substantiated by immunohistochemistry markers CD117, DOG1, and vimentin. Molecular analysis illuminated the role of key oncogenes, primarily KIT and PDGFRA mutations, emphasizing the importance of molecular diagnostics in GIST management. Despite the severity of the presentation, the patient\'s postoperative recovery was favorable, highlighting the effectiveness of prompt surgical and multidisciplinary approaches in managing complex GIST cases.

Caroli\'s syndrome is a congenital disease characterized by dilation of intrahepatic bile ducts and congenital hepatic fibrosis. It is a rare condition in clinical work. Typically, the diagnosis of this disease is confirmed through medical imaging. Here, we report a case of atypical Caroli\'s syndrome in a patient who presented with recurrent upper gastrointestinal tract bleeding. The patient underwent imaging examinations, liver biopsy and whole exome sequencing. The results of the imaging examination were non-specific. However, with the aid of pathological examination, the patient was diagnosed with Caroli\'s syndrome. In conclusion, for cases where the imaging presentation of Caroli\'s syndrome is inconclusive, an accurate diagnosis should rely on pathology. By discussing this specific case, our aim is to enhance readers\' understanding of this disease, provide valuable information that can aid in the early detection and appropriate management of Caroli\'s syndrome, ultimately improving patient outcomes.

Wilms tumor (WT), or nephroblastoma, is an uncommon malignant neoplasm occurring in the kidney of pediatric patients. Its extrarenal location is extremely rare and has been reported in various sites, including the female genital tract, with only 9 cases arising in the uterine corpus. We present the case of an adult woman who underwent total abdominal hysterectomy due to a uterine mass causing persistent abdominal pain. The characteristic triphasic morphology (composed of epithelial, stromal, and blastemal elements) supported by a broad immunohistochemical panel, along with the imaging exclusion of a renal neoplasm, was diagnostic of WT of the uterus. For the first time, a comprehensive genomic profiling of a uterine primary WT was also performed by next-generation sequencing, disclosing alterations at the level of copy number variations in the genes ERBB2, FGFR23, FGF6, FGFR2, and RPS6KB1. All previously reported uterine cases were reviewed, with a summary of their main clinicopathologic characteristics, and the main differential diagnoses are presented. Further reports are needed to improve our knowledge about prognostic factors, clinical behavior and molecular alterations that could guide appropriate therapeutic decision making.

BACKGROUND: Struma ovarii refers to rare mature cystic teratomas containing at least 50% of thyroid tissue, and malignant transformation is known to be even rarer. The synchronous development of malignant struma ovarii and cervical thyroid carcinoma are also scarce and poorly understood due to limited data about molecular features. Here, we present the first report of RET/PTC 1 rearrangement in synchronous metastatic malignant struma ovarii to the abdominal wall and cervical thyroid cancer.
METHODS: We described a 47-year-old multigravida woman with bilateral adnexal and lower abdominal wall masses detected during the evaluation of abnormal uterine bleeding. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and surgical removal of abdominal wall mass. Then, the pathological evaluation revealed papillary thyroid carcinoma (PTC) within struma ovarii and metastatic PTC in the abdominal wall fibro adipose tissue. Further, cervical thyroid gland physical examination and ultrasound illustrated a nodule within the left lobe. Subsequently, a total thyroidectomy was performed, and a histological examination revealed PTC. Furthermore, all affected tissue, i.e., struma ovarii, abdominal wall metastasis, and cervical thyroid gland tested for BRAF and RAS mutations and RET/PTC 1 rearrangement. RET/PTC 1 rearrangement was identified among all three different sites. Finally, after six years of follow-up, the patient had no evidence of recurrence or distant metastasis.
CONCLUSIONS: In light of these findings, malignant struma ovarii might yield a clue to cervical thyroid carcinoma, and the molecular analysis could provide valuable information for understanding the underlying mechanism, tumor clinicopathological behaviors, and prognosis.

Dermatofibrosarcoma protuberans (DFSP) is a rare, CD34+ mesenchymal neoplasm that classically involves the dermis. A COL1A1::PDGFB t(17;22) translocation is present in 91.4% to 96% of cases, resulting in aberrant proliferation due to tyrosine kinase hyperactivity. Here, we present a postmenopausal woman with a CD34-positive spindle cell neoplasm of the breast without cutaneous involvement, lacking muscle marker expression, STAT6 expression, and 13q14 deletion by fluorescence in situ hybridization (FISH). Although the classic PDGFB translocation was not detected by FISH, the overall features were highly suspicious for DFSP. Subsequent RNA-based next-generation sequencing revealed an EMILIN2::PDGFD fusion. A literature review showed that PDGFD fusions can be detected in up to 55% PDGFB FISH negative cases, with EMILIN2::PDGFD fusion highly associated with fibrosarcomatous transformation. This holds important diagnostic and prognostic information as fibrosarcomatous-DFSP is associated with higher recurrence and metastatic potential. The tumor was completely resected with clear margins, showed no fibrosarcomatous areas, and no evidence of recurrence is documented 2 years since resection. This review and case report adds to the literature regarding PDGFD-translocation positive DFSP as a differential diagnosis of CD34-positive spindle cell tumors of the breast, while emphasizing the prognostic importance of EMILIN2::PDGFD fusions.

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BACKGROUND: For patients with non-small cell lung cancer (NSCLC), targeted therapies are becoming part of the standard treatment. It is of question which information the clinicians provide on test requests and how the laboratories adapt test conclusions to this knowledge and regulations.
METHODS: This study consisted of two components; 1) checking the presence of pre-defined elements (administrative and key for therapy-choice) on completed requests and corresponding reports in Belgian laboratories, both for tissue- and liquid biopsy (LB)-testing and b) opinion analysis from Belgian pathologists/molecular biologists and clinicians during national pathology/oncology meetings.
RESULTS: Data from 4 out of 6 Belgian laboratories with ISO-accreditation for LB-testing were analyzed, of which 75% were university hospitals. On the scored requests (N = 4), 12 out of 19 ISO-required elements were present for tissue and 11 for LB-testing. Especially relevant patient history, such as line of therapy (for LB), tumor histology and the reason for testing were lacking. Similarly, 11 and 9 out of 18 elements were present in the reports (N = 4) for tissue and LB, respectively. Elements that pathologists/molecular biologists (N = 18) were missing on the request were the initial activating mutation, previous therapies, a clinical question and testing-related information. For reporting, an item considered important by both groups is the clinical interpretation of the test result. In addition, clinicians (N = 28) indicated that they also wish to read the percentage of neoplastic cells.
CONCLUSIONS: Communication flows between the laboratory and the clinician, together with possible pitfalls were identified. Based on the study results, templates for complete requesting and reporting were proposed.

We present a 29-month-old male patient in follow-up due to pyelocaliceal dilation with a prostatic nodule incidentally found during ultrasound evaluation. Cysto video endoscopy was performed and a prostate biopsy, obtained. Microscopic evaluation showed a haphazardly distributed population of muscular cells with cross striations without evidence of mitosis or necrosis. Immunohistochemistry was positive for myogenin and desmin and negative for smooth muscle actin. Next generation sequencing was performed without finding any pathogenic variant or fusion in the tumor RNA. The patient received no further treatment, remained asymptomatic and continues in follow up, 3 years after initial diagnosis. We report a case of prostate rhabdomyoma in a toddler, an exceptional location that raises concern about differential diagnosis with its malignant counterpart, rhabdomyosarcoma, especially at this age.