INTRODUCTION:Struma ovarii is a rare type of ovarian teratoma consisting predominantly of thyroid tissue and showing a usually benign clinical course which cannot be predicted by its histology. Thus, their molecular analysis could help to better classify these tumors. However, the molecular profile of struma ovarii, especially the benign one, has been rarely studied. MATERIAL AND METHODS:We performed a retrospective, non-interventional study of 23 benign ovarian struma ovarii using formalin-fixed paraffin-embedded tissues for DNA extraction and next-generation sequencing. RESULTS:Two tumors harbored interesting molecular alterations. The first tumor, diagnosed in an adult patient, harbored two DICER1 variants: c. 4738 C > T and c. 5429 A > T. The second one was a struma ovarii harboring a POLD1 c.961G > A, p.(Gly321Ser) variant. None of the tumors harbored BRAF mutations. CONCLUSION:Benign struma ovarii do not harbor BRAF alterations. DICER1 and POLD1 variants need further investigation in this tumor pathology.

Endometrial cancer (EC) is a major gynecologic malignancy whose classification and treatment paradigms are evolving because of molecular profiling. Mutations in DNA polymerases, particularly in DNA polymerase epsilon ( POLE ) and DNA polymerase delta 1 ( POLD1 ), have become central to a subset of ultramutated ECs with crucial clinical and prognostic effects. The molecular mechanisms of POLD1 dysfunction in EC, its clinical manifestations, emerging diagnostic challenges, and therapeutic opportunities are explored in this review. Mutations in the exonuclease domain of POLD1 lead to ultramutation. Recent evidence suggests a unique recessive mechanism where an oncogenic mutation is coupled with the loss of the wild-type allele, abrogating the cell’s ability to correct replication errors. Mutations in 4 conserved acidic residues (D316, E318, D402, and D515)—the DEDD motif—such as p. D402N result in the loss of proofreading capacity and confer a high tumor mutational burden. Small nuclear ribonucleoprotein polypeptide B overexpression in EC also modulates POLD1 splicing, contributing to its oncogenicity. POLD1 -mutant ECs probably represent a subset of the ultramutated molecular category, paralleling POLE -mutated tumors, with implications for diagnostics, genetic counseling, and targeted therapy; their identification necessitates expanded genomic testing, mutational signature analysis, and awareness of their unique splicing and functional biology.

We report a case of a 23-year-old woman with concomitant Takayasu arteritis and nodular sclerosis classic Hodgkin lymphoma, both diagnosed by 18 F-FDG PET/CT. Treatment with ABVD chemotherapy, corticosteroids, and radiotherapy (without additional immunosuppressive therapy) led to parallel remission of both conditions. PET/CT after 2 chemotherapy cycles confirmed a complete metabolic response, sustained over 4 years. This case underscores the key role of 18 F-FDG PET/CT in diagnosing and monitoring both diseases and highlights the rare coexistence and concurrent evolution of large-vessel vasculitis and Hodgkin lymphoma, suggesting a possible paraneoplastic or indirect association that is seldom reported.

The purpose of the present study is to determine whether or not lesion characteristics on PET/CT could reduce the number of samples required to achieve a diagnosis in image-guided bone biopsies (IGBB). A retrospective review of 38 percutaneous IGBB performed at a single center. Biopsies have been performed from January 1st, 2020, to October 23rd, 2024. Inclusion criteria were patients with a PET/CT and a histopathologic report available. Specimens were collected, numbered, and independently analyzed in separate containers. PET/CT data, including SUVmax, SUVmean, MTV, TLG, and morphological lesion characteristics, were correlated with biopsy outcomes and subjected to statistical analysis. Patients were classified by the number of samples needed for diagnosis: first (Group 1), second (Group 2), or third/subsequent (Group 3). Thirty-four/38 (89

Background: The origin of primary mucinous ovarian tumors remains uncertain. Recently, a number of published cases suggested a possible mesonephric origin. The aim of this study is to investigate the association between these two types of proliferation and to determine whether the theory regarding this origin of ovarian mucinous tumors could be further supported. Material and methods: In our retrospective study, we included 406 patients diagnosed with a primary ovarian mucinous tumor. Clinical parameters were extracted from the patients' files. The slides were reexamined to identify any potential mesonephric-like elements. Foci harboring characteristics suggestive of a mesonephric-like component were subjected to an immunohistochemical analysis with GATA3 (Eurobio, L50-823) and TTF-1 (Dako-Agilent, clone 8G7G3/1) antibodies. Results: The mean age at diagnosis was 47.4 years (range 6-94 years). The tumors (n = 417, 15 bilateral cases) were mucinous cystadenomas/cystadenofibromas (n = 305), borderline mucinous tumors (n = 84) and mucinous carcinomas (n = 28). Associated Brenner tumors were present in 16 cases and teratomas in 8 cases. Morphological analysis revealed 64 cases with a component that could be considered mesonephric-like. Two of these were TTF-1 positive and one of them expressed GATA3 weakly and very focally. However, these were interpreted as non-specific of mesonephric differentiation. Conclusion: Our series of 417 ovarian mucinous tumors revealed no associated mesonephric-like components. To date, only eight mucinous tumors associated with mesonephric-like foci have been reported in the literature. Our results indicate that the association between these two types of tissue is probably too rare to imply a potential role in their histogenesis.

Coilin is the signature protein of Cajal bodies (CBs), membrane-less organelles probably acting as sites for post-transcriptional RNA modification. Recent data suggest that coilin may be a regulator of the NF-kB activity, and Hodgkin lymphomas are hallmarks of neoplasms with NF-kB dysregulation. To the best of our knowledge, the immunohistochemical expression of coilin has been never investigated in Hodgkin lymphomas. We herein examined, by immunohistochemistry, full tissue sections of 58 classical Hodgkin lymphomas diagnosed in 31 male and 27 female patients and found that none of the cases expressed coilin. We compared these findings with Coilin expression in diffuse large B-cell lymphomas (DLBCL), where the marker was also negative. This finding represents the first data on coilin in lymphomas and prompts further studies to explore this downregulation.

T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) is a molecule involved in the immune escape of tumour cells and is a target of immunotherapy. Recently, TIGIT has gained attention as a crucial player in the tumour microenvironment (TME) of lymphomas. TIGIT immunohistochemical expression has not been thoroughly studied in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and T-cell-/histiocyte-rich large B-cell lymphoma (THRLBCL). We studied TIGIT's immunohistochemical expression in 27 whole-lymph-node sections from 19 patients diagnosed with NLPHL and eight patients diagnosed with THRLBCL. TIGIT was consistently expressed in the TME of all lymphomas, exhibiting strong membranous staining. The TME expression ranged from 40% to 90% (median 70%). Rosettes around tumour cells were common in 23 (85.1%) cases. TIGIT was expressed by tumour cells in four cases (14.8%). NLPHL and THRLBCL harbour ​extensive TIGIT expression in their microenvironment, often in the form of peritumoural rosettes; some express TIGIT in tumor cells. Despite a small cohort, our results suggest that patients may benefit from TIGIT inhibition.

Special AT-rich sequence-binding protein 2 (SATB2) can distinguish primary ovarian mucinous tumors from ovarian metastases of colorectal or appendiceal tumors. However, its expression in other gynecological localizations remains underexplored. Whole-tumor sections of 376 endometrial and 27 endocervical carcinomas were examined for SATB2 expression. Among endometrial carcinomas, we found 10 cases (2.7%) expressing SATB2, all of which were endometrioid adenocarcinomas. In 8 of them, expression concerned only the morules. Only two cases expressed SATB2 in the glandular component, indicating 0.53% positivity in this cancer group. No stromal expression was detected. One case (3.8%) of endocervical adenocarcinoma focally expressed SATB2. SATB2 expression can be reliably used in the differential diagnosis of primary endometrial endometrioid and serous carcinomas as well as primary endocervical adenocarcinomas because nearly all of these tumors are SATB2-negative. SATB2 positivity in endometrial carcinomas is almost always restricted to morules within endometrioid adenocarcinomas.

Le streptocoque du groupe A (Streptococcus pyogenes) est un pathogène versatile, le plus souvent responsable d’infections non invasives et bénignes mais parfois à l’origine d’infections invasives graves pouvant se compliquer d’un syndrome de choc toxique. La létalité des infections invasives à streptocoque du groupe A, toutes formes confondues, est estimée à 20 % et justifie l’introduction d’une antibiothérapie en urgence. Depuis septembre 2022, il a été observé à l’échelle nationale et européenne une recrudescence des infections non invasives et surtout invasives, en particulier chez les enfants, justifiant une surveillance accrue de ce pathogène. Sont présentés trois cas d’infections invasives à streptocoque du groupe A dont l’évolution a rapidement conduit au décès et pour lesquels une autopsie médico-légale a été réalisée. Il s’agit d’un enfant et de deux adultes, sans antécédent notable en dehors d’un éthylisme chronique pour le cas 2. L’étiologie infectieuse bactérienne était insoupçonnée et aucun d’entre eux a fait l’objet d’examens complémentaires avant le décès. Des symptômes respiratoires associés à une infection virale concomitante étaient rapportés pour les cas 1 et 2. Il a été observé une fasciite nécrosante d’un membre, sans porte d’entrée cutanée identifiée, pour les cas 2 et 3. Les analyses bactériologiques ont isolé Streptococcus pyogenes dans de multiples sites pour chacun des cas. Ce travail souligne l’importance de l’autopsie médico-légale dans l’identification de Streptococcus pyogenes lorsque celui-ci n’est pas suspecté avant le décès. Il est alors possible de prendre part au dispositif d’alerte mais aussi de déclencher des mesures préventives dans l’entourage des cas.

Lipoleiomyomas are rare variants of uterine leiomyomas rarely studied in the literature. We retrospectively studied 20 cases of uterine lipoleiomyomas showing that these lesions represent 0.7% of all uterine leiomyomas diagnosed histologically. The patients did not experience any recurrence, and the tumors showed no morphological criteria of malignancy. They did not show significant p16, p53 or MiB1 expression. They showed diffuse and strong expression or estrogen and progesterone receptors by the smooth muscle component but without accompanying expression by the adipocytic component in one third of the cases. Androgen receptors were rarely expressed. They expressed in their majority HMGA2 in both components, while RB1 was usually not found. Fumarate hydratase (FH) is expressed by lipoleiomyomas, while they are negative for HMB45. In conclusion, uterine lipoleiomyomas are rare, benign tumors, characterized by HMGA2 expression, while they show no elements suspicious of malignancy, PEComas or FH deficiency. The role of RB1 in these tumors should be further explored.

Background: Since the advent of laparoscopic hysterectomy, several studies have described artefacts, such as vascular pseudoinvasion, constituting potential pitfalls in the histological evaluation of these specimens. The use of an intrauterine manipulator is often suggested as the factor creating these artefacts. Objectives: To describe possible artefacts, such as vascular pseudoinvasion, myometrial clefts, and tumor cells in the lumen of the cervix, on the serosa, and in the tubal lumen, and to correlate them with clinical and pathological characteristics. Material and Methods: This is a retrospective monocentric study of 60 patients having been treated for benign (n = 27, 45%) or malignant (n = 33, 55%) uterine pathologies. Results: Vascular pseudoinvasion was found in 13 (22%) adenocarcinomas and in one (2%) benign uterine pathology. Clefts within the myometrium were observed in 16 (27%) uteri. Cells in the tubal lumen were observed in six (10%) hysterectomies. True vascular emboli were not correlated with the use of an intrauterine manipulator (p = 0.47) or the type of surgery (p = 0.21). Vascular pseudoinvasion was correlated with the presence of tumor cells in the lumen of the cervix (p = 0.013) and the presence of clefts in the myometrium (p < 0.001), but not with the other factors studied. Conclusions: Overall, in our series, we did not observe any statistical association between the use of an intrauterine manipulator and the presence of true emboli or vascular pseudoinvasion during hysterectomy in women with malignant or benign uterine pathologies. Vascular pseudoinvasion was also associated with the presence of other artefacts.

BACKGROUND:Papillary hidradenomas (PHs) of the anogenital region are uncommon tumors whose immunohistochemical and molecular profile have been infrequently studied.MATERIAL AND METHODS:We studied 15 PHs by next-generation sequencing and 10 immunohistochemical markers (PAX8, GATA3, HER2, MSH6, PMS2, estrogen, progesterone and androgen receptors, CK14, and NKX3.1).RESULTS:All cases expressed GATA3, whereas none expressed PAX8, and rare tumor cells were NKX3.1-positive. Almost all cases expressed estrogen receptors (ER), progesteron receptors (PR), and androgen receptors (AR). CK14 was expressed by myoepithelial cells, whereas only rarely by the epithelial tumor cells. HER2 showed no significant expression. Immunohistochemical expression for the mismatch repair proteins showed persistence in all cases. Molecular analysis often showed PIK3CA mutations, as well as KRAS , SMO , and MAP2K1 mutations.CONCLUSION:Anogenital PHs frequently harbor PIK3CA mutations and show a PAX8-, GATA3/ER/PR/AR + immunohistochemical profile.

Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a recent disease concept whose physiopathology remains largely unknown. Association of TAFRO syndrome features with immune-mediated or hematologic disorders have been reported but have not been reported with chronic myelomonocytic leukemia. Chronic myelomonocytic leukemia (CMML) is a myeloproliferative/myelodysplastic syndrome that is frequently associated with autoimmune or autoinflammatory features. Herein, we report 2 cases of CMML-associated TAFRO syndrome-like symptoms. The first one was fatal, and the second one was successfully treated with siltuximab. These reports question the Masaki criteria for TAFRO syndrome diagnosis, which require excluding an autoimmune, neoplastic, or infectious condition beforehand.

While several treatment choices exist for cervical cancer, such as surgical therapy, chemotherapy, and radiotherapy, some patients will still show poor prognosis. HPV infection is a principal factor for cervical cancer development, from early inflammation to proliferation, angiogenesis, and neoplastic growth. While HPV T-cell responses exist, the tumor seems to evade the immune system upon its tolerance. The latter suggests the existence of a confluent tumor microenvironment responsible for the evasion tactics employed by the neoplasm. Therefore, novel biomarkers governing prognosis and treatment planning must be developed, with several studies tackling the significance of the tumor microenvironment in the genesis, development, proliferation, and overall response of cervical cancer during neoplastic processes. This review aims to analyze and contemplate the characteristics of the tumor microenvironment and its role in prognosis, progression, evasion, and invasion, including therapeutic outcome and overall survival.

BackgroundOvarian fibromas are benign tumors that can present peculiar morphological features not studied sufficiently.Material and MethodsIn this retrospective study, 75 consecutive cases of ovarian fibroma were morphologically compared with 46 thecomas, 16 granulosa cell tumors, and 5 sclerosing stroma tumors for the following factors: the growth pattern as diffuse or nodular, the presence of hyaline plaques, necrosis, keloid-like sclerosis, calcifications, cystic degeneration, fibrous or edematous stroma, prominent vascularity, lutein cells, cellularity, scant or abundant cytoplasm, prominent cell membranes, nuclear grooves, atypia, and mitotic activity.ResultsThe tumors differed significantly in terms of hyaline plaques presence, nuclear grooves, growth pattern, stroma type, tumor cellularity, cytoplasm, prominence of cell membranes, atypia, mitotic activity, and prominent vascularity.ConclusionOvarian fibromas can present some maybe unexpected features rather frequently, such as cystic degeneration, hyaline plaques, prominent vascularity, increased cellularity, and some mitotic activity, thus their presence should not always prompt to an alternative diagnosis.

Gastrointestinal tactile corpuscle-like bodies are a rare, incidental, entirely benign finding. It is mainly reported in the colorectum and esophagus/gastro-esophageal junction. Rare cases have been documented in the stomach. Here, we present two cases of gastric and colonic tactile corpuscle-like bodies of a 38-year-old female and a 55-year-old male, respectively. Endoscopically, the colonic lesion was resected as an adenomatous polyp, while the gastric biopsies were taken to rule out Helicobacter pylori (H. pylori) gastritis. Microscopically, both specimens revealed the same histopathologic aspects of eosinophilic fibrillary material with round to oval cells and peripherally placed nuclei. Immunohistochemically, these lesions were positive for anti-S100, confirming the diagnosis of tactile corpuscle-like bodies. A thorough literature review is provided.

The latest WHO classification of the female genital tract tumors introduces a new type of carcinoma: the primary gastric-type (or gastro-intestinal type) carcinoma of the endometrium. This type of neoplasm tends to have a poor outcome, making its correct diagnostic important. As little is known about this entity and given its quite challenging diagnosis, we aim to review existing data about it and propose a practical diagnostic approach. There are currently 11 cases published in 8 articles fitting the precise definition of a primary gastric-type carcinoma of the endometrium. Three main differential diagnoses must be excluded before considering this tumor: endometrioid adenocarcinoma with mucinous (Müllerian-type) differentiation, endocervical primary, and gastro-intestinal primary. Morphological aspects of this tumor can be heterogeneous and confusing; in this context, immunochemistry can be helpful to highlight the gastric or intestinal differentiation, but also to eliminate a mucinous endometrioid adenocarcinoma of Müllerian-type, by the constant negativity of estrogen receptors. A metastasis of a primary gastro-intestinal tract carcinoma must also be excluded by clinical, endoscopic and imaging work-up. Finally, an endometrial extension of a primary endocervical gastric-type carcinoma should be ruled out by complete sampling of the cervix. Intestinal type endocervical adenocarcinoma is easier to eliminate since this is an HPV-associated neoplasm.

Autophagy is implicated in normal pregnancy and various pathologic pregnancy conditions. Its presence in hydatidiform moles (HM) is unknown. We immunohistochemically studied 36 HM for LC3B and p62 to precisely determine their expression in the decidua, endometrium, and villi. Nineteen nonmolar pregnancies were also studied. LC3B was found in almost half of the villi and p62 was found in almost all villi. LC3B expression was significantly higher in complete HM than in partial HM. LC3B showed different expression patterns in trophoblast layers. LC3B and p62 expression was higher in molar than nonmolar pregnancies. Autophagic markers are present in HM and their expression differs between complete and partial moles.

It has been suggested that a primary tumor can "prepare" the draining of lymph nodes to "better accommodate" future metastatic cells, thus implying the presence of a premetastatic lymph node niche. However, this phenomenon remains unclear in gynecological cancers. The aim of this study was to evaluate lymph-node draining in gynecological cancers for premetastatic niche factors, such as myeloid-derived suppressor cells (MDSCs), immunosuppressive macrophages, cytotoxic T cells, immuno-modulatory molecules, and factors of the extracellular matrix. This is a monocentric retrospective study of patients who underwent lymph-node excision during their gynecological-cancer treatment. In all, 63 non-metastatic pelvic or inguinal lymph nodes, 25 non-metastatic para-aortic lymph nodes, 13 metastatic lymph nodes, and 21 non-cancer-associated lymph nodes (normal controls) were compared for the immunohistochemical presence of CD8 cytotoxic T cells, CD163 M2 macrophages, S100A8/A9 MDSCs, PD-L1+ immune cells, and tenascin-C, which is a matrix remodeling factor. PD-L1-positive immune cells were significantly higher in the control group, in comparison to the regional and distant cancer-draining lymph nodes. Tenascin-C was higher in metastatic lymph nodes than in both non-metastatic nodes and control lymph nodes. Vulvar cancer-draining lymph nodes showed higher PD-L1 values than endometrial cancer and cervical cancer-draining lymph nodes. Endometrial cancer-draining nodes had higher CD163 values and lower CD8 values, compared to vulvar cancer-draining nodes. Regarding regional draining nodes in low- and high-grade endometrial tumors, the former showed lower S100A8/A9 and CD163 values. Gynecological cancer-draining lymph nodes are generally immunocompetent, but vulvar cancer draining nodes, as well as high-grade endometrial cancer draining nodes, are more susceptible to harboring premetastatic niche factors.