Surgical management of a large neurilemmoma-like leiomyoma of the uterine cervix mimicking a retroperitoneal tumor.

•A large cervical neurilemmoma-like leiomyoma can simulate a retroperitoneal tumor.•They are extremely rare tumors that require adequate bleeding control.•Comprehensive anatomo-pathological study should be done to rule out malignancy.

Müllerian adenosarcoma of the uterine cervix with sarcomatous overgrowth: A case report of aggressive disease in a young patient.

INTRODUCTION: Müllerian adenosarcoma of the cervix with sarcomatous overgrowth and lymphovascular invasion is a rare and aggressive disease. We report a case of a young patient with Müllerian adenosarcoma with sarcomatous overgrowth in the uterine cervix and pelvic lymph node involvement. The patient received radical surgery but not adjuvant treatment, and the disease was aggressive with rapid relapse. PRESENTATION OF CASE: A 39-year-old woman was diagnosed with Müllerian adenosarcoma of the cervix with sarcomatous overgrowth, International Federation of Gynecology and Obstetrics (FIGO) stage IB2. She underwent abdominal radical hysterectomy and resection of the left external iliac lymph nodes for suspected metastatic involvement detected during surgical exploration but undetected via imaging. She refused adjuvant treatment, and the disease recurred 8 months after primary oncologic surgery, with rapid local, regional, and bone relapse. DISCUSSION: Our report suggests that sarcomatous overgrowth, a high mitotic index, a rhabdomyoblastic component, and lymphovascular compromise are risk factors for aggressive recurrence. Positron emission tomography-computed tomography (PET-CT) was used to identify relapse locations in addition to those detected via clinical examination of the vaginal vault. However, whether PET-CT is indicated for the initial detection of lymph node and bone metastases in FIGO stage IB tumors with surgical indication is unclear. CONCLUSION: A young woman with Müllerian adenosarcoma of the cervix with sarcomatous overgrowth presenting the risk factors for its recurrence experienced a rapid relapse after receiving radical surgery but not adjuvant therapy. Control of this aggressive disease via sequential radiotherapy and chemotherapy are recommended.

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.

AIMS: 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. METHODS AND RESULTS: Twenty-five YSTs showing either classical patterns (CPs) of histology (microcystic/reticular, n = 14; polyvesicular, n = 1; and hepatoid, n = 1) or somatic glandular patterns (SGPs; n = 9) were analysed for expression of α-fetoprotein (AFP), glypican-3 (GPC3), villin, hepatocyte paraffin-1 (HepPar-1), CDX2, SALL4 and LIN28. AFP expression was constantly heterogeneous in CPs but tended to be focal/absent in SGPs. GPC3 was diffuse in CPs but heterogeneous (seven cases) or focal/absent (two cases) in SGPs. HepPar-1 expression was focal in all but three cases (diffuse in one CP-hepatoid and two SGPs). CDX2 positivity was focal in CPs but heterogeneous (seven cases) or diffuse (two cases) in SGPs. Villin, SALL4 and LIN28 were diffusely positive in nearly all cases. CONCLUSIONS: CPs reproduce the immunophenotype of HYS and early endoderm with variable expression of both AFP and markers of early gut or hepatic differentiation. SGPs with intestinal differentiation often have incomplete immunophenotypes. A differential diagnosis panel, including both markers of pluripotentiality (SALL4 and/or LIN28) and endoderm (AFP, GPC3 and villin), is proposed. It identifies overlapping multidifferentiation of primitive and somatic immunophenotypes, supporting the recently proposed term of primitive endodermal tumours.

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 SLIDES: The 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.

Papel de los nuevos marcadores inmunohistoquímicos en los tumores de células germinales malignos gonadales / The role of new immunohistochemical markers in malignant germ cell tumours of the gonads

Los tumores de células germinales malignos (TCGM), debido a su tratamiento individualizado, se presentan como un reto diagnóstico y terapéutico donde el estudio inmunohistoquímico reproducible es de suma importancia. Revisamos el valor diagnóstico de nuevos anticuerpos provenientes de investigaciones de células madre tales como OCT3/4, SOX2 y SALL4. Su expresión en los TCGM confirma una vez más el carácter pluripotencial de estas neoplasias. El SALL4 puede ser considerado un marcador general de los TCGM. La expresión de OCT3/4 en disgerminoma/seminoma lo confirma como precursor de otros TCGM. La expresión simultánea de SALL4, SOX2 y OCT3/4 confirman al carcinoma embrionario como el tumor de células madre pluripotenciales, con SOX2 y CD30 como marcadores altamente característicos. El D2-40 es útil para diferenciar el disgerminoma/seminoma del carcinoma embrionario. La alfa-fetoproteína es diagnóstica de tumores vitelinos, pero en casos de escasa expresión, la reevaluación positiva con GLP3 y SALL4 y la negatividad frente al OCT3/4 confirman el diagnóstico. Un panel mínimo de anticuerpos con cobertura de los tipos más frecuentes de los tumores de células germinales debería incluir alfa-fetoproteína, CD30, D2-40, OCT3/4, GLP3 y SALL4(AU)

Malignant germ cell tumours (MGCT) of the ovary and testis often represent a diagnostic challenge due to their frequent overlap and primitive histology. New antibodies, mostly originating from the stem cell research field, provide accurate tools for the identification of different tumour types. The expression of antibodies such as OCT3/4, SOX2 and SALL4 indicates the pluripotent character of these neoplasms. SALL4 represents a good screening antibody for the diagnosis of MGCT while OCT3/4 indicates a totipotential role for dysgerminoma/seminoma. OCT3/4, SOX2 and SALL4 are coexpressed in embryonal carcinoma, where SOX2 and CD30 represent highly specific markers. D2-40 podoplanin is useful to differentiate dysgerminoma/seminoma from embryonal carcinoma. AFP is highly diagnostic of yolk sac (endodermal primitive) tumours but in cases with low expression, diagnosis is facilitated by a concurrent positivity of Glypican3 and SALL4 and OCT3/4 negativity. An antibody panel that includes alpha-foetoprotein, CD30, D2-40, OCT3/4, Glypican3 and SALL4 is useful in the identification and taxonomy of MGCT(AU)

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.

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.

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.