Extragonadal yolk sac tumor of the ureter with neuroendocrine differentiation: A case report

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the ‘‘Surgical Pathology Cancer Case Summary (Checklist)’’ portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of these documents.

Adjuvant chemotherapy for surgically resected non–small cell lung cancer

Germ cell tumors (GCTs), rare malignancies that occur in a wide range of locations and display variable histologic patterns, may pose diagnostic challenges. Glypican 3 (GPC3), a membrane-bound heparan sulfate proteoglycan, has been shown to be a novel diagnostic marker in testicular GCT. However, GPC3 expression in ovarian and extragonadal GCT has not been reported. We evaluated GPC3 immunoreactivity in GCTs from 63 patients (57 children and 6 adults), including 14 ovarian and 20 extragonadal primary GCTs and 8 metastases along with 21 primary testicular GCTs for comparison. All 33 yolk sac tumors (YSTs) and both choriocarcinomas were immunoreactive for GPC3. In contrast, a minority of immature (4/10) and mature (4/35) teratomas were positive. No positivity was seen in 6 embryonal carcinomas or 5 germinomas. GPC3 is differentially expressed in ovarian and extragonadal GCTs, with expression predominantly observed in YSTs and choriocarcinoma.

ObjectiveEven though the primary mediastinal extragonadal germ cell tumors (EGCTs) are rare, they are noteworthy in the differential diagnosis of mediastinal masses. In this study, we aimed to identify the clinical features of mediastinal malignant GCTs and compare the results of hematopoietic stem cell transplantation between mediastinal and nonmediastinal malignant EGCTs.MethodData of the patients with EGCT who were treated and underwent hematopoietic stem cell transplantation at our hospital between 1988 and 2015 were retrieved retrospectively. Results were compared between mediastinal and nonmediastinal EGCTs.ResultsData of 65 patients diagnosed with EGCT (37 [56.92%] cases with mediastinal EGCT and 28 [43.07%] cases with nonmediastinal EGCT) were assessed. The clinical stages, frequency of pretransplant status, mean pretransplant time, and mean number of chemotherapy lines before hematopoietic stem cell transplantation were not significantly different between groups. Although the overall survival did not significantly differ between groups, the 5-year survival was significantly higher in mediastinal EGCTs (P=0.02). Yolk sac tumor was significantly more common in mediastinal EGCTs (P=0.05). Mortality rates were higher in seminomas and yolk sac tumors in all cases, higher in embryonal carcinomas in mediastinal EGCT group and higher in yolk sac tumors in nonmediastinal EGCT group. While choriocarcinomas had more aggressive courses in mediastinal EGCTs, seminomas and yolk sac tumors had poorer prognosis in nonmediastinal EGCTs. Short pretransplant time and persistence of elevated posttransplant βhCG and AFP levels were the significant mortality risk factors both in mediastinal and nonmediastinal EGCTs.ConclusionMediastinal placement of EGCT was not a poor prognostic factor; furthermore, the 5-year survival was significantly higher in mediastinal EGCTs. According to our knowledge, this is the first study that compares the clinical outcomes of hematopoietic stem cell transplantation of mediastinal and nonmediastinal malignant EGCTs.

Extragonadal germ cell tumors (EGCTs) are rare tumors that predominantly affect young males. They are located in the body midline. The most common sites of EGCTs are the mediastinum (50-70%), the retroperitoneum (25-40%), the pineal gland (5%), and the sacrococcygeal area (less than 5%). 2-5% of germ cell tumors are considered of extragonadal origin. The anatomical distribution of EGCTs might be explained by the migration of primordial germ cells from the yolk sac along the hindgut and its mesentery to the genital ridges. EGCTs are considered to develop from pluripotent embryonal stem cells that because of conditions in the midline of the embryo have undergone germ cell differentiation. Presentation of EGCTs is often in an advanced local stage and with distant metastases. At diagnosis a testicular primary tumor should by all means be excluded. There is strong evidence that a considerable amount of EGCTs, especially retroperitoneal EGCTs have in fact a regressed primary testicular tumor. Treatment is based on localization, histology and extent of disease. Chemotherapy is often first line treatment. Surgery is advocated for teratomas and residual disease.

Simple SummaryBreast tumors exhibiting neuroendocrine differentiation are a heterogeneous group of tumors that have been variously defined in previous World Health Organization (WHO) classifications. In the WHO Classification of Tumours, 5th edition, neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) of the breast, both of which are invasive cancers, are classified as neuroendocrine neoplasms (NENs) of the breast. However, the clinical significance of NE differentiation in breast cancers, especially in NETs of the breast, is not yet fully understood, and a large overlap appears to exist between breast cancers showing NE differentiation and invasive breast cancer of no special type (IBC-NST). While breast NECs show distinct clinical and morphological features, diagnosis of NETs based on the morphological characteristics alone can be challenging; one reason is that breast NETs do not necessarily have the same morphological characteristics as those of NENs arising in other organs. Thus, the heterogeneity of breast tumors with neuroendocrine differentiation and the changes in their classifications over the years have left many open issues that still need to be resolved. In this review, we shall summarize the history of breast “NENs,” including of mixed types of tumors and the characteristics of these tumors, and discuss their differences from NENs arising in other organs.Breast tumors with neuroendocrine (NE) differentiation comprise an uncommon and heterogeneous group of tumors, including invasive breast cancer of no special type (IBC-NST) with NE features, neuroendocrine tumors (NETs), and neuroendocrine carcinoma (NEC). The most recent World Health Organization (WHO) classification in 2019 defined neuroendocrine neoplasms (NENs) of the breast (Br-NENs) as tumors in which >90% of cells show histological evidence of NE differentiation, including NETs (low-grade tumors) and NEC (high-grade). Due to the low prevalence of these tumors and successive changes in their diagnostic criteria over the years, only limited evidence of these tumors exists, derived mainly from case reports and retrospective case series. Breast tumors with NE differentiation are usually treated like the more commonly occurring IBC-NSTs. Immunohistochemistry (IHC) of breast tumors with NE differentiation usually shows a hormone receptor (HR)-positive and human epidermal growth factor type 2 (HER2)-negative profile, so that hormonal therapy with cyclin-dependent kinase (CDK)4/6 inhibitors or other targeted agents would be reasonable treatment options. Herein, we present a review of the literature on breast tumors with NE differentiation as defined in the latest WHO 2019 classification, and discuss the clinical management of these tumors.

MIXED GERM CELL TUMOR PRESENTING AS LARGE MEDIASTINAL MASS

A CASE REPORT OF A PRIMARY YOLK SAC TUMOR OF THE ANTERIOR MEDIASTINUM

Male extragonadal germ cell tumors (EGCTs) are characterized by a malignant transformation of germ cells without the presence of a gonadal primary tumor. EGCTs represent up to 5% of all germ cell tumors (GCTs) with an incidence around 1/1,000,000. It is assumed that EGCTs either derive from a malignant transformation of germ cells that were misdirected during embryogenesis, or from germ cells that have spread throughout the body during embryogenesis to fulfil different roles in immunological processes or distinct organ functions. EGCTs are mainly localized along the median axis, especially in the mediastinum and in the retroperitoneum. Regarding histology, they have the same subtypes as gonadal GCTs (seminomas and non-seminomas). EGCTs are normally diagnosed in advanced stages due to tumor-associated symptoms or as incidental finding during routine diagnostic or therapeutic procedures. An integral part of EGCT treatment is cisplatinum-based chemotherapy: residual tumor resection is only indicated for non-seminomatous EGCTs. The prognosis of malignant retroperitoneal EGCTs depends on tumor localization and histology. The 5-year overall survival ranges from 40% to 90% and is more favorable for retroperitoneal or seminomatous tumors than for mediastinal non-seminomatous tumors. Mature teratomas of mediastinal EGCTs are benign and are only treated by surgical resection.

ED08.03 Adjuvant Chemotherapy of Completely Resected

345 Background: Extragonadal germ cell tumors (EGGCT) are very rare and account for only 2% to 5% of all malignant germ cell neoplasms. Although multimodality treatment, including cisplatin-based chemotherapy and postchemotherapy surgery, has improved the prognosis of patients with EGGCT, few findings are available for these tumors. We therefore performed a retrospective analysis of Japanese patients with EGGCT. Methods: We performed a retrospective review of the medical records of 34 male patients ranging in age from 18 to 62 years (median age, 30 years) treated at our institution between 1982 and 2010. Fifteen patients (44%) had primary mediastinal EGGCT, 16 patients (47%) had primary retroperitoneal EGGCT, and three patients (9%) had primary mediastinal and retroperitoneal EGGCT. Results: Twenty-six patients (76%) had nonseminomatous EGGCT, and eight patients (24%) had seminomatous histology. Surgical procedures were performed in five patients (15%) as induction treatment. Three of them had seminomatous histology and were continuously disease-free after adjuvant chemotherapy. Twenty-nine patients (85%) had received cisplatin-containing regimen as induction therapy. Twenty-three patients underwent post–chemotherapy surgery, and 14 of them (60%) had residual viable malignant cells. On univariate analysis, nonseminomatous EGGCT (P<0.01) and resistance to cisplatin (lack of achievement of CR/PRm- by induction chemotherapy; P<0.01) were identified as negative prognostic factors for survival. Twenty of 34 patients (59%) were alive without disease, and 13 patients with nonseminomatous histology died of disease progression. The overall 10-year survival rate for all patients was 53%. Conclusions: Patients with seminomatous EGGCT have a very good prognosis, while nonseminomatous histology and resistance to cisplatin were found to be negative prognostic factors.

We reviewed the European Group for Blood and Marrow Transplantation (EBMT) experience with salvage high-dose chemotherapy (HDC) in paediatric patients with extragonadal germ-cell tumour (GCT). A total of 23 children with extragonadal GCT, median age 12 years (range 1–20), were treated with salvage HDC with haematopoietic progenitor cell support. The GCT primary location was intracranial site in nine cases, sacrococcyx in eight, retroperitoneum in four, and mediastinum in two. In all, 22 patients had a nongerminomatous GCT and one germinoma. Nine patients received HDC in first- and 14 in second- or third-relapse situation. No toxic deaths occurred. Overall, 16 of 23 patients (70%) achieved a complete remission. With a median follow-up of 66 months (range 31–173 months), 10 (43%) are continuously disease-free. Of six patients who had a disease recurrence after HDC, one achieved a disease-free status with surgical resection followed by chemotherapy and radiotherapy. In total, 11 patients (48%) are currently disease-free. Eight of 14 patients (57%) with extracranial primary and three of nine patients (33%) with intracranial primary GCT are currently disease-free. HDC induced impressive long-term remissions as salvage treatment in children with extragonadal extracranial GCTs. Salvage HDC should be investigated in prospective trials in these patients.

Extragonadal germ cell tumors are uncommon, and although they morphologically resemble their gonadal counterparts, unexpected gonadal presentation increases the potential for erroneous diagnoses. Yolk sac tumor is a malignant germ cell tumor characterized by an extraembryonic yolk sac line of differentiation, and relative to other germ cell tumors, is characterized by varied and diverse histologic patterns. When occurring outside of typical age parameters or in extragonadal locations, the histologic variability of yolk sac tumor and its tendency to mimic somatic tumors pose diagnostic challenges. Because extragonadal yolk sac tumor of the vulva is very rare, with only isolated case reports and small series in the literature, it is often not considered in the differential diagnosis. As both prognosis and management of yolk sac tumor differ significantly from those of somatic tumors, accurate diagnosis is essential. This review discusses histologic features of extragonadal yolk sac tumor, addresses somatic tumors arising in the vulva for which yolk sac tumor may be confused, and provides guidance with respect to the use of immunohistochemistry in the diagnosis of yolk sac tumor.

Extragonadal germ cell tumors (EGGCTs) are rare malignancies that arise outside the gonads and occur infrequently in the gastrointestinal tract. Their presentation often mimics that of other abdominal neoplasms, posing diagnostic challenges. Histopathological and immunohistochemical confirmation, along with tumor marker evaluation, is essential for diagnosis. Early diagnosis and platinum-based chemotherapy can significantly improve patient outcomes. A 25-year-old male presented with abdominal pain, a palpable mass in the umbilical region, and subacute intestinal obstruction. Imaging revealed a heterogeneously enhancing lesion in the mesentery and a subcapsular lesion in the left kidney. Emergency debulking surgery was then performed. Histopathology and immunohistochemistry confirmed an EGGCT favoring a yolk sac tumor. Serum marker levels were elevated with AFP (alpha-fetoprotein) of 854 IU/mL, 23 mIU/mL of β-human chorionic gonadotrophin (β-hCG); 277 U/L of LDH. Ultrasonography of the testes revealed microcalcifications in the left testis, without overt malignancy. The patient was diagnosed with a Stage IIIC extragonadal non-seminomatous germ cell tumor. He was started on an EP regimen owing to poor pulmonary function, followed by BEP, and was scheduled for a high inguinal orchidectomy. This case highlights the importance of including EGGCTs in the differential diagnosis of abdominal masses in young males. A multidisciplinary approach with timely histological and oncological assessments is vital. Early intervention with platinum-based chemotherapy offers a favorable prognosis, even in advanced stages. Given the rarity of this presentation, further studies are needed to refine diagnostic and therapeutic strategies.

On the basis of seminal studies in the 1980s, appreciable histologic heterogeneity, ranging from 45% to 70% of cases, may be encountered in lung cancer. However, the epidemiologic and histologic landscape of lung cancer in the last 3 decades has radically changed. In this study, 172 consecutive surgically resected primary lung carcinomas evaluated from 2010 to 2012 were entirely sampled and examined according to current histologic classifications. In 129 cases, a positive preoperative biopsy was also available. Major histologic heterogeneity (a single tumor showing at least 2 different histologic types) and minor histologic heterogeneity (a single tumor showing just 1 histologic type but at least 2 different growth patterns) were evaluated in all cases. Immunohistochemical heterogeneity (ie, "aberrant" staining) was also assessed using a panel of markers of adenocarcinoma (TTF-1, napsin, and CK7), squamous cell carcinoma (p63, CK5/6), and neuroendocrine differentiation (chromogranin and synaptophysin), both on positive biopsies and surgical specimens. Overall, major and minor histologic heterogeneity on resections were disclosed in 4% (7 cases) and 50.6% (87 cases), respectively, whereas just 1 case of minor heterogeneity (pleomorphic carcinoma) was observed on biopsies. Minor heterogeneity was limited to adenocarcinomas (82.6%, 81/98 cases) and sarcomatoid carcinomas (6 pleomorphic types among 8 sarcomatoid carcinomas). Immunohistochemical heterogeneity was recorded in 22.6% of the cases, with expression of p63 and CK5/6 in a subset of adenocarcinomas (25 cases, 25.5%), CK7 in 17.4% of squamous cell carcinomas, and synaptophysin in 6 cases of non-neuroendocrine tumors (4%, 6/155). The high rate of adenocarcinomas, accounting for 57% (98 cases) of 172 consecutively resected lung cancers, reflects the new scenario of thoracic oncology and may explain the significant lower rate of major histologic heterogeneity (4%) and the higher frequency of different architectural patterns (minor heterogeneity) that we found in lung cancer compared with previous studies.