Isabel Dulcey

Germ cell tumors of the ovary: an update.

CONTEXT The field of ovarian germ cell tumors (OGCTs) has remained relatively unchanged in the last 2 decades. However, the introduction of new stem cell pluripotency markers has provided a new understanding into the identification and taxonomy of OGCT types. New data have provided new insights into unusual teratoma-associated autoimmune disorders and the origin of gliomatosis peritonei. OBJECTIVE To review the impact of new pluripotency markers in the diagnosis of malignant OGCT (MOGCT) and analyze new nomenclature proposals and clinicopathologic entities. DATA SOURCES Ovarian germ cell tumors from routine material and expert consultation files at San Cecilio University Hospital, Granada, Spain, and the relevant literature were reviewed. CONCLUSIONS Although a correct diagnosis of MOGCT can often be made with histologic and classic immunohistochemical studies, the new immunohistochemical pluripotency markers give higher diagnostic accuracy. Germ cell tumors represent a caricature of the phases of normal embryonic differentiation from primordial germ and stem cells to extraembryonal and somatic tissue differentiation. Since every stage of differentiation and its related tumor type exhibit characteristic markers, the analysis of their expression facilitates tumor typing, thus complementing the use of classic antibodies. They also allow a more precise evaluation of the degree of immaturity in teratoma. The new term, primitive endodermal tumors, simplifies the understanding of the complex histology of the yolk sac tumor group, as this terminology encompasses its multiple endodermal differentiations. Recently described autoimmune encephalitis due to antibodies against the N-methyl-d-aspartate receptor has become the most frequent autoimmune disorder associated with ovarian teratoma.

A diagnostic immunohistochemical panel for yolk sac (primitive endodermal) tumours based on an immunohistochemical comparison with the human yolk sac

To establish a diagnostic immunohistochemical panel for various histotypes of yolk sac (primitive endodermal) tumours (YSTs) by comparison with the human yolk sac (HYS) immunophenotype.

Gliomatosis peritonei as a natural experiment in tissue differentiation

Gliomatosis peritonei (GP) is an unusual condition in which nodules of mature astroglia, often miliary and microscopic in size, are widespread in the peritoneum and abdominal lymph nodes. Its behaviour is benign and it is usually found in association with ovarian teratoma and rarely with teratomas of other organs. Implants grow rapidly and can remain unchanged for life. Astroglia is the main component, but other neural lineage elements and many other tissues can be found. Cells are mature but not terminal, since they express SOX2. Secondary associated lesions include: a) degenerative astrocytic changes, b) granulomatous and follicular chronic inflammatory changes, c) association with hormonally related changes, such as decidual peritoneal metaplasia and endometriosis and d) endothelial and adventitial vascular hyperplasia leading to haemoperitoneum.Two pathogenetic mechanisms are considered: direct seeding of immature neural cells from a primary tumour with subsequent differentiation and metaplasia from peritoneal stem cells. The former proposal is supported by clinicopathologic data such as ample cellular heterogeneity, coexistence of mature astroglia with neural blastema, as well as the shed keratin and hairs from the ovarian neoplasm. However, metaplasia is sustained by a heterozygosity pattern of GP nodules, identical to the normal tissue and different from the coexistent ovarian teratoma. GP would constitute a response to growth factors from teratoma or macrophages. While an implantative origin from ovarian teratoma remains in most cases a more probable mechanism, metaplasia from peritoneal stem cells would explain cases of GP which present a monomorphic astrocytic cell population.

The secondary human yolk sac has an immunophenotype indicative of both hepatic and intestinal differentiation

Although the microscopy of the secondary human yolk sac (SHYS) is well known, few studies have addressed its immunohistochemical profile. The SHYS is involved in the synthesis, absorption and transfer of various proteins and behaves as a temporary liver and intestine. The objective of this study was to evaluate the presence of immunohistochemical markers of hepatic and intestinal function in the SHYS. We performed a retrospective histological and immunohistochemical study of 26 SHYS from spontaneous abortions and tubal pregnancies, 15 of which were from the 7th to 8th week. The antibodies used were against alpha-foetoprotein (AFP), glypican 3 (GLP3), hepatocyte-paraffin-1 (HepPar-1), villin, CDX2, SALL4 and podoplanin (D2-40). Early SHYS from the 5th to the 8th week revealed a network of intracellular vesicles communicating with the lumen of endodermal tubules that were highlighted by intense membrane AFP expression. Endodermal cells consistently expressed AFP, GLP3, SALL4, hep-par-1, villin and CDX2, while mesothelial cells only expressed D2-40. The endodermal layer of the SHYS from the 5th to the 8th week revealed a transient canalicular network which was highlighted by strong membranous AFP expression; this may represent the substrate of a SHYS transport system during its period of maximal activity. The synthetic and transfer functions of the yolk sac endoderm were reflected in a hybrid immunophenotype in which proteins characteristic of hepatic function such as AFP, GLP3, SALL4 and hep-par-1 were coexpressed simultaneously with others such as villin and CDX2, indicative of an intestinal role.

Urothelial carcinoma of the renal pelvis with simultaneous trophoblastic and malignant clear cell endodermal-type differentiation

Embryonal-type differentiations in urothelial neoplasms areuncommon [1, 2].These frequently underdiagnosed phenom-ena may include either the presence of trophoblastic areas or,even more rarely, admixed yolk sac tumour patterns(YST)[2].Wepresentforthefirsttimetheassociationofbothtrophoblasticandmalignantendodermal-typeelementswithinan aggressive high-grade urothelial carcinoma (HGUC).Due to the presence of the endodermal component,which had cells with a prominent clear cytoplasm, adifferential diagnosis with other papillary and clear cellrenal neoplasms was necessary.Clinical historyA 47-year-old male presented with intense pain in the lum-bar region. Seventeen years previously, he had been treatedfor a non-seminomatous testicular tumour with lung andliver metastases. He eventually underwent a right orchid-ectomy followed by platinum-based chemotherapy. Follow-up showed only residual mature teratomatous tissue in thebiopsy material from the remaining testicle.On his recent admission, elevated levels of serum β-hCGof 9,897.06 mUI/ml (normal 0–2.6 mUI/ml) and a lactatedehydrogenase of 1,280 U/L (normal 0–480 U/l) werefound. Serum α-foetoprotein (AFP) was negative. A CTscan showed a large, ill-defined retroperitoneal mass involv-ing the left kidney and ureter. There was marked infiltrationof the psoas, and lung and vertebral metastases were prom-inent. No lesions were detected in the left testicle after bothclinical and ultrasonographical exploration. A left ureter-onephrectomy with resection of the surrounding tissueswas performed. Patient refused chemo- or radiotherapyand 18 months after diagnosis is alive but has a largeresidual mass and pulmonary metastases.Materials and methodsThe ureteronephrectomy specimen was bivalved andfixed overnight in 10% buffered formalin and routinelyprocessed. Seven tissue blocks were taken, and H&E-stained sections were analysed. Immunohistochemistrywas performed on representative sections with the anti-bodies shown in Table 1.

Necrotic mature ovarian teratoma associated with anti-N-methyl-d-aspartate receptor encephalitis

A 20-year-old female with a diagnosis of autoimmune encephalitis against N-methyl-D-aspartate receptor was found to have a 13 mm teratoma in the left ovary. The tumor had undergone massive coagulative necrosis within a normal ovary, a previously unreported feature. Necrosis of a mature cystic teratoma is very rare in the absence of ovarian torsion. It is proposed that necrosis may have induced a massive liberation of neuronal antigens. The vast majority of the tumors associated with this newly described condition are ovarian teratomas containing neural tissues. In this paper, we review their different histopathological aspects that may explain the relative incidence of various tumor types associated to this form of encephalitis. Anti N-methyl-D-aspartate receptor encephalitis has now become the most frequent autoimmune disorder associated with ovarian teratoma.

Finding apotropaic images in dermatopathology.

Apotropaic, meaning to cast aside, from ancient Greek apotropaios (ἀποτρόπαιος), from ἀποτρέπω, from ἀπό (away) and τρέπω (flip), is a term referring to a type of traditional magic common to many cultures. Intending to ward off evil, objects (amulets, charms) or body gestures were employed, some of these are considered nowadays as obscene (gesto dell’ombrello, far manichetta, bras d’honneur, corte de mangas—Italian, French, and Spanish respectively, for the V-sign). Apotropaic objects to ward off the evil eye often include depictions of hands (the khomsah or hand of Fatima or Miriam in Muslim and Jewish cultures, respectively), eyes, and generative organs such as the vulva (the Carthaginian Tanit sign and medieval Sheela na Gigs sculptures from churches in Ireland and Britain) and phalli, which in many Far Eastern cultures (lingam) to the Mediterranean, were used in a mystical way but are devoid of any erotic or obscene component, being found 473356 IJSXXX10.1177/1066896912473356Internati onal Journal of Surgical PathologyAneiros-Fernandez et al.

Case report: Papillary mesothelioma of the peritoneum with foamy cell lining

A 34-year-old female, with a history of continued asbestos exposure, presented with a papillary peritoneal mesothelioma with a diffuse, prominent clear foamy cell change, with microvacuolation in its papillary lining, that expressed cytokeratins 7, 5/6 and calretinin as well as nuclear WT-1 and apical membrane staining for thrombomodulin, podoplanin D2-40 and HBME-1. In contrast, lining cells were CD68 negative. Foamy cell change has been reported in isolated cases as solid cords but not as a diffuse change in the mesothelial papillary lining. This phenomenon prompts differential diagnoses with abdominal and renal papillary clear cell tumours, which were discarded after a characteristic mesothelial immunophenotype was demonstrated.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4679576081031834.

Coexistence of placental site nodule and cervical squamous carcinoma in a 72-year-old woman.

We report a unique case of the coexistence of cervical cancer and placental site nodule (PSN) in a 72-year-old multiparous woman presenting with vaginal bleeding. She had undergone tubal sterilization 30 years before. On admission, she had profuse vaginal bleeding, and a bulky cervical mass was seen on vaginal examination. Histology revealed the coexistence of a moderately differentiated invasive squamous cell carcinoma with a PSN in its stroma. Its immunohistochemistry revealed characteristic phenotypes for both lesions--the squamous carcinoma was strongly positive for p16. The intermediate trophoblasts of the PSN showed a diffuse positivity for CAM 5.2, human placental lactogen, CD10, and α-inhibin and, focally, for human chorionic gonadotropin. This is the first report on the coexistence of these 2 lesions in an elderly postmenopausal patient and demonstrates that PSN can be found after the menopause as an unexpected lesion in this age group, mimicking various cervical malignancies.