Somatic-type malignancies (SMs) in patients with testicular germ cell tumors (GCT) are rare and mostly attributed to "transformation" of teratoma, although yolk sac tumor (YST) origin has also been proposed. We studied 124 cases of "SM" of testicular GCT origin from 106 patients to evaluate their morphology, immunohistochemical features (especially the utility of SALL4), and relationship to YST. Primitive neuroectodermal and nephroblastomatous tumors were excluded because of prior studies. Patients ranged in age from 15 to 68 years (mean, 33 y). The tumors ranged from 0.7 to 30 cm (mean, 7.6 cm) and involved the retroperitoneum (64%), abdomen/pelvis (10%), lung (10%), mediastinum (6%), supraclavicular region/neck (4%), testis (4%), and thigh (1%). Most initial diagnoses were sarcomas (n=68) or carcinomas (n=51). On review and immunohistochemical analysis, 7 of 45 adenocarcinomas were reclassified as glandular YSTs (GYST) on the basis of glypican-3 (GPC3) and/or α-fetoprotein positivity and scant/absent reactivity for EMA and CK7. These occasionally (29%) had subnuclear and sometimes supranuclear vacuoles (endometrioid-like), whereas adenocarcinomas were more frequently mucinous (17%) or enteric-type (11%) than endometrioid-like (9%). Both expressed CDX2 frequently (83% and 63%, respectively). MUC protein 2, 4, 5, and 6 expression was more common in adenocarcinomas (7% to 36%) than in GYSTs (0% to 20%) but was infrequent. Both were often positive for SALL4, BerEP4, and MOC31; all were negative for TTF-1. On follow-up (GYST: range, 23 to 169 mo; mean, 81mo; adenocarcinoma: range, 1 to 170 mo; mean, 55 mo), 50% and 33% of patients with GYST and adenocarcinoma, respectively, died of disease. We reclassified 26 of 76 sarcomatoid tumors as sarcomatoid YSTs (SYST) on the basis of positive reactivity for both AE1/3 and GPC3. These tumors often had spindled and epithelioid cells in a fibromyxoid stroma. SYSTs were often (60%) SALL4 positive, whereas sarcomas were all negative. On follow-up (SYST: range, 1 to 259 mo; mean, 62 mo; sarcoma: range, 1 to 327 mo; mean, 70 mo), 50% and 29% of patients with SYST and sarcoma, respectively, died of disease, with most mortality occurring in those with high-grade tumors. We conclude that, on the basis of a panel of immunoreactivities, a significant number of "SMs" in testicular GCT patients are more accurately classified as either GYSTs or SYSTs. Ambiguous glandular tumors should be evaluated for GPC3, α-fetoprotein, CK7, and EMA reactivity and sarcomatoid ones for GPC3, AE1/3, and SALL4 reactivity.

Sarcomatoid neoplasms in patients with testicular germ cell tumors (TGCTs) may show diverse lineages and are usually attributed to "transformation" of teratoma, although origin from yolk sac tumor (YST) has also been suggested. We evaluated 33 sarcomatoid tumors from 23 TGCT patients that lacked specific features of a defined sarcoma subtype for a number of features, including: atypia (mild, moderate, severe), cellularity, tumor necrosis, mitotic index, stromal vascularity, cell profile (spindle or epithelioid), and stromal quality (myxoid and/or fibrous). Immunohistochemical staining analyses directed against cytokeratin (AE1/AE3), SALL4, glypican-3 (GPC3), α-fetoprotein (AFP), p63, glial fibrillary acidic protein (GFAP), CD34, MUC4, smooth muscle actin (SMA), desmin, caldesmon, and myogenin were performed. Staining intensity (0=negative, 1=weak, 2=moderate, 3=strong) and extent (0=<1%, 1=1% to 10%, 2=10% to 50%, 3=>50%) were scored. Tumor grade based on the French sarcoma grading system was assessed, with grades 2-3 considered high grade. Tumors with at least moderate intensity and >10% (+) cells for both AE1/AE3 and GPC3 were considered to be sarcomatoid YST (SYST); 22 tumors from 14 patients (ages 18 to 38 y, mean 27 y) met these criteria and were the focus of this study. All SYSTs occurred after chemotherapy (3 to 132 mo after TGCT diagnosis; mean 42.5 mo, median 30.5 mo). They had spindled (100%; 19 predominant) and epithelioid cells (77%; 3 predominant) in myxoid to fibrous stroma. Thirteen exhibited at least focally severe nuclear atypia. Distinctive tumor "ringlets" and intercellular basement membrane deposits (parietal YST differentiation) were common. In addition to positivity for AE1/AE3 and GPC3, 15/22 were SALL4 (+), 10/22 were at least focally CD34 (+), and 2/22 were focally p63 (+). Fifty percent exhibited smooth muscle differentiation as evidenced by desmin (8/19), caldesmon (2/4), and/or SMA (4/6) reactivity. AFP, MUC4, GFAP, and myogenin were negative in all cases. On follow-up, 8/14 patients died of disease at 7 to 217 months (mean 58 mo) after the initial SYST diagnosis, whereas 5/14 were alive and had no evidence of disease (ANED) at 1 to 259 months (mean 83 mo). One patient died of unrelated causes at 39 months. Of the 11 patients with high-grade tumors, 8 were dead of disease, 1 died of an unrelated cause, and 2 were ANED; all 3 patients with low-grade tumors were ANED at 41 to 262 months (mean 128 mo). We conclude that a high proportion of sarcomatoid tumors in postchemotherapy resections of TGCT patients are SYSTs. These typically occur several years after diagnosis and behave aggressively when high grade.

Fine-needle aspiration (FNA) is a well-established diagnostic tool in adult patients, and while in recent years it has gained popularity in the pediatric population, it is still far less universally accepted in children than in adults. A computerized search of our tertiary medical center's laboratory information system was performed for the 20-year period from 1992 to 2012. All FNAs in children 12 years of age and younger and all related surgical pathology reports were identified. Cytologic and histologic diagnoses were stratified into six diagnostic categories--benign, atypical, suspicious, malignant, cyst contents, and nondiagnostic--and then compared to determine the utility of FNA in this patient population. Four hundred and three FNAs in 389 patients were included in this study, of which there were 288 benign (71.5%), 8 atypical (2.0%), 10 suspicious (2.5%), 42 malignant (10.4%), 12 cyst contents (3.0%), and 43 nondiagnostic (10.6%) cases. The most common benign diagnoses were reactive lymph node and inflammatory infiltrate/abscess, while the most common malignant diagnoses were leukemia/lymphoma, rhabdomyosarcoma, and neuroblastoma. Of the 127 FNAs (31.5%) with histologic follow-up, we identified just one false positive and one false negative case. Like FNA in adults, this study shows that the technique is both sensitive (97.2%) and specific (98.5%), and has high positive predictive (97.2%) and negative predictive (98.5%) values for diagnosing malignancy in childhood. As FNA is a simpler, less invasive, and more cost-effective procedure when compared with surgical biopsy, it represents a valuable diagnostic tool in the pediatric population.

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Autoimmune hepatitis is a chronic necroinflammatory disease of unknown etiology that is characterized by increased aminotransferases, serum autoantibodies, increased immunoglobulin G levels, and histological interface hepatitis. The disease does not have a pathognomonic clinical, laboratory, or histological feature; diagnosis depends on a combination of clinical and pathologic criteria which also form the basis for a weighted scoring system to aid diagnosis. Liver biopsy is an essential part of the diagnostic criteria and is also crucial to the management of the disease. This review focuses on the diagnosis, microscopic features, differential diagnosis and overlap syndromes of autoimmune hepatitis.