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Head and Neck Pathology Jun 2022SMARCB1 (INI1) deficient carcinoma (SDC) is a newly-described, aggressive, high-grade malignancy of the adult population. Rarely, these tumors demonstrate yolk sac... (Review)
Review
SMARCB1 (INI1) deficient carcinoma (SDC) is a newly-described, aggressive, high-grade malignancy of the adult population. Rarely, these tumors demonstrate yolk sac differentiation. Treatment protocols are not defined due to the rarity of this entity. A 55 year-old-male presented with a tumor originating in the maxillary sinus. He was treated with neoadjuvant therapy followed by radical surgery and adjuvant treatment. We review the literature and discuss the course of disease and treatments of sinonasal SDC with yolk sac tumor differentiation. To our knowledge, this is the sixth reported case of sinonasal SDC with yolk sac tumor differentiation. This is the first publication describing the clinical course and efficacy of therapeutic interventions.
Topics: Adult; Biomarkers, Tumor; Carcinoma; Endodermal Sinus Tumor; Humans; Male; Middle Aged; SMARCB1 Protein
PubMed: 34420180
DOI: 10.1007/s12105-021-01375-9 -
Molecular Medicine (Cambridge, Mass.) Mar 2023Being the standard-of-care for four decades, cisplatin-based chemotherapy is highly efficient in treating germ cell tumors (GCT). However, often refractory patients...
BACKGROUND
Being the standard-of-care for four decades, cisplatin-based chemotherapy is highly efficient in treating germ cell tumors (GCT). However, often refractory patients present with a remaining (resistant) yolk-sac tumor (YST(-R)) component, resulting in poor prognosis due to lack of novel treatment options besides chemotherapy and surgery. The aim of this study was to identify novel targets for the treatment of YST by deciphering the molecular mechanisms of therapy resistance. Additionally, we screened the cytotoxic efficacy of a novel antibody-drug-conjugate targeting CLDN6 (CLDN6-ADC), as well as pharmacological inhibitors to target specifically YST.
METHODS
Protein and mRNA levels of putative targets were measured by flow cytometry, immunohistochemical stainings, mass spectrometry of formalin-fixed paraffin-embedded tissues, phospho-kinase arrays, or qRT-PCR. Cell viability, apoptosis and cell cycle assays of GCT and non-cancerous cells were performed using XTT cell viability assays or Annexin V / propidium iodide flow cytometry, respectively. Druggable genomic alterations of YST(-R) tissues were identified by the TrueSight Oncology 500 assay.
RESULTS
We demonstrated that treatment with a CLDN6-ADC enhanced apoptosis induction specifically in CLDN6 GCT cells in comparison with non-cancerous controls. In a cell line-dependent manner, either an accumulation in the G2 / M cell cycle phase or a mitotic catastrophe was observed. Based on mutational and proteome profiling, this study identified drugs targeting the FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling pathways as promising approaches to target YST. Further, we identified factors relevant for MAPK signaling, translational initiation and RNA binding, extracellular matrix-related processes as well as oxidative stress and immune response to be involved in therapy resistance.
CONCLUSIONS
In summary, this study offers a novel CLDN6-ADC to target GCT. Additionally, this study presents novel pharmacological inhibitors blocking FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling for the treatment of (refractory) YST patients. Finally, this study shed light on the mechanisms of therapy resistance in YST.
Topics: Humans; Endodermal Sinus Tumor; Neoplasms, Germ Cell and Embryonal; Claudins
PubMed: 36991316
DOI: 10.1186/s10020-023-00636-3 -
Modern Pathology : An Official Journal... Aug 2021Mesonephric carcinoma of the cervix is a rare tumor derived from Wolffian remnants. Mesonephric-like carcinomas of the ovary and endometrium, while morphologically...
Mesonephric carcinoma of the cervix is a rare tumor derived from Wolffian remnants. Mesonephric-like carcinomas of the ovary and endometrium, while morphologically similar, do not have obvious Wolffian derivation. Here, we sought to characterize the repertoire of genetic alterations in primary mesonephric and mesonephric-like carcinomas, in the distinct histologic components of mixed cases, as well as in matched primary tumors and metastases. DNA from microdissected tumor and normal tissue from mesonephric carcinomas (cervix, n = 8) and mesonephric-like carcinomas (ovarian n = 15, endometrial n = 13) were subjected to sequencing targeting 468 cancer-related genes. The histologically distinct components of four cases with mixed histology and four primary tumors and their matched metastases were microdissected and analyzed separately. Mesonephric-like carcinomas were underpinned by somatic KRAS mutations (25/28, 89%) akin to mesonephric carcinomas (8/8, 100%), but also harbored genetic alterations more frequently reported in Müllerian tumors. Mesonephric-like carcinomas that lacked KRAS mutations harbored NRAS (n = 2, ovary) or BRAF (n = 1, endometrium) hotspot mutations. PIK3CA mutations were identified in both mesonephric-like (8/28, 28%) and mesonephric carcinomas (2/8, 25%). Only mesonephric-like tumors harbored CTNNB1 hotspot (4/28, 14%) and PTEN (3/13, 23%) mutations. Copy number analysis revealed frequent gains of chromosomes 1q and 10 in both mesonephric (87% 1q; 50% chromosome 10) and mesonephric-like tumors (89% 1q; 43% chromosome 10). Chromosome 12 gains were more frequent in ovarian mesonephric-like carcinomas, and losses of chromosome 9 were more frequent in mesonephric than in mesonephric-like carcinomas (both p = 0.01, Fisher's exact test). The histologically distinct components of four mixed cases were molecularly related and shared similar patterns of genetic alterations. The progression from primary to metastatic lesions involved the acquisition of additional mutations, and/or shifts from subclonal to clonal mutations. Our findings suggest that mesonephric-like carcinomas are derived from a Müllerian substrate with differentiation along Wolffian/mesonephric lines.
Topics: Adult; Aged; Female; Genital Neoplasms, Female; Humans; Mesonephroma; Middle Aged; Mutation
PubMed: 33772212
DOI: 10.1038/s41379-021-00799-6 -
Oncology (Williston Park, N.Y.) Sep 1996Whether patients with clinical stage I nonseminomatous testicular germ-cell cancer (NSGCT) should be treated with orchiectomy and retroperitoneal lymph node dissection... (Review)
Review
Whether patients with clinical stage I nonseminomatous testicular germ-cell cancer (NSGCT) should be treated with orchiectomy and retroperitoneal lymph node dissection (RPLND) or orchiectomy and surveillance remains controversial. Proponents of the former approach cite the uncertainty and risks of monitoring young men who may harbor occult metastases, while proponents of the latter strategy contend that surgical staging overtreats 60% to 70% of men. Over the last few years, prognostic factors in the primary testicular tumor have helped clinicians make more rational decisions about whether RPLND or surveillance should follow initial orchiectomy. As of 1996, the most clinically useful prognostic factors are the percentage of embryonal carcinoma and the presence or absence of vascular invasion by tumor cells in the primary tumor. Ongoing work with flow cytometry, image analysis, proliferation markers, and oncogene and tumor-suppressor gene markers may allow us to further stratify patients as to their likelihood of occult metastases and permit rational "risk-adaptive" treatment.
Topics: Adult; Biomarkers, Tumor; Endodermal Sinus Tumor; Genetic Markers; Germinoma; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Orchiectomy; Prognosis; Retroperitoneal Space; Risk Factors; Risk Management; Testicular Neoplasms
PubMed: 8882926
DOI: No ID Found -
BMC Women's Health Jun 2023Yolk sac tumour (YST) is the second most common ovarian germ cell tumour and usually presents in children and young women. However, tumours rarely occur as malignant...
BACKGROUND
Yolk sac tumour (YST) is the second most common ovarian germ cell tumour and usually presents in children and young women. However, tumours rarely occur as malignant gynaecological tumours with YST components.
CASE PRESENTATION
We present one case of endometrioid carcinoma and clear cell carcinoma with YST components and two other cases of YSTs associated with high-grade serous carcinoma of the ovary in females. After surgery and adjuvant chemotherapy, the patient with endometrioid carcinoma had progressive disease and died 20 months later, and the other two were still alive at the last follow-up.
CONCLUSIONS
To our knowledge, these mixed neoplasm associations are unusual, and these cases illustrate the diagnosis and prognosis of YST associated with malignant gynaecological tumours, emphasizing early recognition and aggressive treatment.
Topics: Female; Humans; Adenocarcinoma, Clear Cell; Carcinoma, Endometrioid; Endodermal Sinus Tumor; Genital Neoplasms, Female; Ovarian Neoplasms
PubMed: 37391759
DOI: 10.1186/s12905-023-02495-w -
AJNR. American Journal of Neuroradiology Jul 2022Primary intracranial pure yolk sac tumor is very rare. Our aim was to summarize the characteristics of primary intracranial pure yolk sac tumors from the clinical and...
BACKGROUND AND PURPOSE
Primary intracranial pure yolk sac tumor is very rare. Our aim was to summarize the characteristics of primary intracranial pure yolk sac tumors from the clinical and imaging aspects in a retrospective study.
MATERIALS AND METHODS
We studied 5 patients with primary intracranial pure yolk sac tumors in Guangzhou Women and Children's Medical Center from January 2015 to June 2021. A comprehensive literature search was performed on the electronic database of the China National Knowledge Infrastructure (1990 to June 2021). Clinical data based on age, sex, treatment, CT, and MR imaging findings were collected and analyzed.
RESULTS
A total of 25 patients were included in the study, 21 boys and 4 girls. Twenty-one patients underwent plain MR imaging and an enhanced examination, 9 patients underwent DWI, and 12 patients underwent plain CT and/or an enhanced examination. The tumors were posterior fossa in 9 cases and supratentorial in 16 cases. All tumors showed marked enhancement after enhanced scanning by MR imaging or CT. The signal on DWI was similar to that of the cerebral cortex, and the ADC map was similar to or slightly higher than that of the cerebral cortex. Among the cases, 13 were followed up from 2 months to 5 years. There was no recurrence or metastasis in 9 patients with postoperative chemotherapy or chemoradiotherapy followed up for 1.5-5 years. Four patients died 2 months to 1.5 years after only an operation, or chemoradiotherapy but no operation.
CONCLUSIONS
There are some relatively specific imaging findings of primary intracranial yolk sac tumors that could assist in their diagnosis. Surgery combined with radiation therapy and/or chemotherapy can achieve a better prognosis.
Topics: Adolescent; Child; China; Endodermal Sinus Tumor; Female; Humans; Male; Prognosis; Retrospective Studies
PubMed: 35798388
DOI: 10.3174/ajnr.A7556 -
Medicine Apr 2019Yolk sac tumors (YSTs) are malignant germ cell tumors that secrete alpha-fetoprotein (AFP). These tumors commonly develop in infants, young children, and young women and... (Review)
Review
RATIONALE
Yolk sac tumors (YSTs) are malignant germ cell tumors that secrete alpha-fetoprotein (AFP). These tumors commonly develop in infants, young children, and young women and often originate in the gonads. Primary endometrial YST is a very rare malignancy, and a primary endometrial YST in the absence of abnormal AFP levels is even rarer.
PATIENT CONCERNS
A 38-year-old woman presented with the chief complaint of prolonged menstruation and increased menstrual bleeding with a duration of more than 2 months.
DIAGNOSES
Postoperative pathology confirmed a diagnosis of endometrial YST with metastasis to the greater omentum (stage IVB).
INTERVENTIONS
The patient underwent a laparoscopic extrafascial hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy, abdominal para-aortic lymphadenectomy, omentectomy, and appendectomy. Additionally, she received 6 courses of multidrug chemotherapy (bleomycin, etoposide, and cisplatin; BEP).
OUTCOMES
After completing chemotherapy, the patient underwent regular follow-up examinations. No recurrence was noted during a 24-month follow-up period.
LESSONS
YST is mainly treated using surgery and chemotherapy, which may spare endocrine functions in young patients. The BEP regimen appears to be an effective postoperative chemotherapy regimen for patients with endometrial YST.
Topics: Adult; Diagnosis, Differential; Endodermal Sinus Tumor; Endometrial Neoplasms; Female; Humans; Omentum; Peritoneal Neoplasms
PubMed: 30985686
DOI: 10.1097/MD.0000000000015144 -
Taiwanese Journal of Obstetrics &... Nov 2019To report a rare case of endometrial yolk sac tumor (YST) and review published cases of YST of the endometrium. (Review)
Review
OBJECTIVE
To report a rare case of endometrial yolk sac tumor (YST) and review published cases of YST of the endometrium.
CASE REPORT
A 68-year-old female presented with intermittent vaginal spotting for nine months. An endometrial biopsy showed adenocarcinoma. Complete surgical staging operation was performed and the final pathology revealed stage II endometrial yolk sac tumor. The post-operative α-fetoprotein (AFP) level was 133.4 ng/mL. Post-operative adjuvant chemotherapy with bleomycin, etoposide, and cisplatin (BEP) regimen was prescribed for 6 cycles. AFP levels were normal before the fourth cycle of chemotherapy. She is disease free 6 months after completion of therapy.
CONCLUSION
Primary YSTs arising in the endometrium is an extremely rare disease especially in postmenopausal women. Complete surgical staging operation with adjuvant chemotherapy will lead to good outcome in this disease.
Topics: Aged; Antineoplastic Agents; Biopsy; Chemotherapy, Adjuvant; Endodermal Sinus Tumor; Endometrial Neoplasms; Endosonography; Female; Humans; Hysterectomy; Laparotomy; Vagina
PubMed: 31759539
DOI: 10.1016/j.tjog.2019.09.020 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Dec 2019Primary mediastinal yolk sac tumor, which is also known as endodermal sinus tumor, is a rare but lethal neoplasm and its prognosis is very dismal. The current treatment...
OBJECTIVE
Primary mediastinal yolk sac tumor, which is also known as endodermal sinus tumor, is a rare but lethal neoplasm and its prognosis is very dismal. The current treatment for this tumor is controversial, and chemotherapy combined with resection of residual lesions is adopted sometimes. We summarized the experience of seven primary mediastinal yolk sac tumors treated with platinum-based chemotherapy and extended resection in Peking University First Hospital.
METHODS
Clinicopathological data of the patients with primary mediastinal yolk sac tumor who received operation in Peking University First Hospital between August 2014 and August 2018 were collected and analyzed retrospectively.
RESULTS
We experienced seven primary mediastinal yolk sac tumors during this period. Computed tomography scan revealed an anterior mediastinal tumor in all the patients and all of them had markedly raised alphafetoprotein (AFP) and normal β-human chorion gonadotropin (β-HCG). Five patients underwent needle core biopsy before treatment, which showed a mediastinal yolk sac tumor. All of these patients received preoperative platinum-based chemotherapy and they all presented partial response according to computed tomography. Two other patients did not receive preoperative biopsy, so they directly underwent extended resection. All of the seven patients underwent operation successfully and two of them experienced postoperative complications, including one with pneumonia and the other with atelectasis. R0 resection was achieved in six patients and R1 resection was achieved in the other patient. According to postoperative pathology, there were one microcyst subtype, one adenoid subtye, one giant capsule subtype and two hybrid subtypes. Surprisingly, there were no yolk sac tumor tissue in the other two patients after preoperative chemotherapy. All the patients received postoperative chemotherapy, excluded one patient who was unable to tolerate chemotherapy after operation. Three patients experienced postoperative pulmonary metastases within one year and two of them died soon. The other patient received chemotherapy and immunotherapy after recurrence and he was alive at the time of writing. Four other patients were alive without recurrence and metastasis.
CONCLUSION
Primary mediastinal yolk sac tumor is rare and its prognosis is poor. A multimodality approach including adjuvant chemotherapy and resection of residual lesions is the optimal treatment and it may lead to long-term survival.
Topics: Endodermal Sinus Tumor; Humans; Male; Mediastinal Neoplasms; Mediastinum; Neoplasm Recurrence, Local; Retrospective Studies
PubMed: 31848510
DOI: 10.19723/j.issn.1671-167X.2019.06.020 -
Cancer Cytopathology Aug 2019Mesonephric adenocarcinomas are rare neoplasms which most commonly arise in the lateral cervix and vagina. Tumors with similar morphologic, immunophenotypic, and...
BACKGROUND
Mesonephric adenocarcinomas are rare neoplasms which most commonly arise in the lateral cervix and vagina. Tumors with similar morphologic, immunophenotypic, and molecular characteristics recently have been described in the uterine corpus and ovary. Herein, the authors sought to characterize the cytomorphologic features of adenocarcinomas exhibiting mesonephric-like differentiation arising in the upper gynecologic tract.
METHODS
Institutional databases were queried retrospectively for tumors of the upper gynecologic tract described as a "tumor of Wolffian origin" or "with mesonephric features" between 2007 and 2017. All available cytologic material was reviewed. Cytomorphologic characteristics were evaluated by 3 pathologists.
RESULTS
The current study cohort consisted of 8 cases taken from 7 patients. Primary sites included the ovary (3 cases); endometrium (4 cases); and pelvis, not otherwise specified (1 case). All cases demonstrated tight 3-dimensional clusters of overlapping cells. Additional architectural features included tubular (5 of 8 cases; 63%) and papillary (3 of 8 cases; 38%) formations. Cells were small with scant (7 of 8 cases; 88%) to moderate (1 of 8 cases; 12%) cytoplasm. Three of the 8 cases (38%) demonstrated extracellular hyaline globules. Nuclei were uniform in size (6 of 8 cases; 75%) or showed mild anisonucleosis (2 of 8 cases; 25%). Nuclear grooves and indentations were observed in all cases. Mitoses (5 of 8 cases; 63%) and apoptotic bodies (4 of 8 cases; 50%), when present, were rare. No necrosis was noted.
CONCLUSIONS
Adenocarcinomas exhibiting mesonephric-like differentiation show a monotonous population of small cells with scant to moderate cytoplasm and abundant nuclear grooves arranged in tight, overlapping, 3-dimensional clusters. Occasionally, papillary or tubular architecture, as well as extracellular hyaline globules, may be seen. These features should prompt further testing (eg, immunohistochemistry) to confirm the diagnosis and to exclude potential mimics.
Topics: Adenocarcinoma; Adult; Aged; Endometrial Neoplasms; Endometrium; Female; Humans; Mesonephroma; Middle Aged; Ovarian Neoplasms; Ovary; Retrospective Studies
PubMed: 31318491
DOI: 10.1002/cncy.22160