ABSTRACT
We present a family in which four individuals have been identified with the same likely pathogenic genetic alteration in the PIK3CA gene at the germinal level; specifically, c.1145G>A p.(Arg382Lys) missense type. The index case patient was diagnosed with multinodular goiter and breast cancer at 61 years old. Among the other three carrier relatives: one has been diagnosed with serous cystadenoma of the ovary and a thyroid nodule with no radiological suspicion of malignancy; the other two present multinodular goiter. Additionally, a sister of three of the carriers suffered from an ovarian teratoma, follicular thyroid carcinoma on multinodular goiter, and high-grade serous ovarian carcinoma. No direct mutation study was performed on her as she had died due to ovarian carcinoma. This finding suggests that the PIK3CA gene should be considered in Cowden-like families when no other gene mutations have been found. Furthermore, this report contributes to characterization of the clinical phenotype caused by mutations in PIK3CA, which may be shared with other hereditary breast and ovarian cancer syndromes.
Subject(s)
Breast Neoplasms , Class I Phosphatidylinositol 3-Kinases , Hamartoma Syndrome, Multiple , Ovarian Neoplasms , Humans , Class I Phosphatidylinositol 3-Kinases/genetics , Female , Hamartoma Syndrome, Multiple/genetics , Hamartoma Syndrome, Multiple/pathology , Middle Aged , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Pedigree , Adult , Phosphatidylinositol 3-Kinases/genetics , Male , Mutation, Missense , Mutation , Aged , Goiter, Nodular/genetics , Goiter, Nodular/pathologyABSTRACT
Background: Squamous cell carcinoma (SCC) arising in a sacrococcygeal pilonidal sinus is rare, with cases of metastatic disease being even rarer. Among published cases, almost none have reported on systemic treatment. Objective: This disease has a poorer prognosis than other forms of cutaneous SCC; therefore, our objective is to shed some light on the treatment of metastatic disease. Methods: We present a series of nine cases treated at a single center, four of whom received systemic treatment. Additionally, other previously reported cases of metastatic disease are included in an attempt to draw stronger conclusions. Results: Four patients were treated under several treatment regimens, with a median progression-free survival of only 2 months and two instances of partial response (18%). The best result was achieved with cemiplimab. Across all the cases, there was a trend toward a benefit of the use of systemic treatment (HR 0.41, 95% CI 0.15-1.12, p = 0.083; median overall survival 13 vs. 8 months). Limitations: Limitations include the significant lack of information on previously published cases and the extremely heterogeneous nature of the existing information. Conclusion: The initial systemic treatment should be an anti-PD-1, as with other SCCs. After progression on anti-PD-1, there is no strong evidence to support the recommendation of a specific treatment or sequence: options include cetuximab and/or chemotherapy (platinum, paclitaxel, 5-fluorouracyl).
ABSTRACT
Peptide receptor radionuclide therapy (PRRT) is an established treatment in advanced neuroendocrine tumors (NETs), which overexpressed somatostatin receptors. However, after progression there are a limited number of available treatments. We want to share a case report about a patient with a NET re-treated with 177Lu-DOTATATE and a literature review about salvage treatment with PRRT. We present a 26-year-old man who started with pelvic pain and after a biopsy of a retro-rectal mass observed in a magnetic resonance was diagnosed with an advanced neuroendocrine tumour. After progression to lanreotide, everolimus and sunitinib, treatment with 177Lu-DOTATATE was initiated, achieving an excellent response with a progression free survival (PFS) of 38 months. At the time of progression, re-treatment with 177Lu-DOTATATE was decided, showing a new partial response, which is currently stable after 15 months. The patient had not presented significant treatment-related toxicity. Although there are no randomized phase III trials or a consensus about the number or dose of cycles, there is evidence about the efficacy and low toxicity of salvage treatment with 177Lu-DOTATATE in NETs. Median progression-free survival ranges from 6 to 22 months. Toxicity is mostly hematologic (anemia and neutropenia), 4-7% grade 3/4.