Mammary mesenchymal and fibroepithelial lesions: An illustrated cytomorphologic update with differential diagnoses.

The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the "Yokohama System"), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo-cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates.

Mesenchymal Tumors with EWSR1 Gene Rearrangements.

Among the various genes that can be rearranged in soft tissue neoplasms associated with nonrandom chromosomal translocations, EWSR1 is the most frequent one to partner with other genes to generate recurrent fusion genes. This leads to a spectrum of clinically and pathologically diverse mesenchymal and nonmesenchymal neoplasms, variably manifesting as small round cell, spindle cell, clear cell or adipocytic tumors, or tumors with distinctive myxoid stroma. This review summarizes the growing list of mesenchymal neoplasms that are associated with EWSR1 gene rearrangements.

New advances in the molecular classification of pediatric mesenchymal tumors.

Pediatric soft tissue tumors are relatively rare and show significant overlap in morphology and immunoprofile, often posing diagnostic and management challenges. Thus, their classification remains often subjective or lumped under "unclassified categories," as a number of lesions lack objective and reproducible criteria in diagnosis. Although in a subset of cases immunohistochemistry has been proved useful to identify a specific line of differentiation, most tumors lack a readily defined histogenesis, being characterized by a rather non-specific immunoprofile. Furthermore, tumors with an ambiguous diagnosis are difficult to grade and their risk of malignancy or clinical management remains uncertain. Advances in molecular genetics, including the more wide application of next generation sequencing in routine clinical practice, have improved diagnosis and refined classification based on objective molecular markers. Importantly, some soft tissue tumors in children are characterized by recurrent gene fusions involving either growth factors (eg, PDGFB) or protein kinases (eg, ALK, ROS, NTRK, BRAF), which have paved the way for new targeted treatments that block the respective upregulated downstream pathways. However, the majority of gene fusions or mutations detected in soft tissue tumors result in an abnormal function of transcription factors or chromatin remodeling. The present review focuses on the latest genetic discoveries in the spectrum of both benign and malignant pediatric soft tissue neoplasia. These genetic abnormalities promise to provide relevant insight for their proper classification, prognosis, and treatment. The entities discussed herein are grouped either based on their shared genetic mechanism or based on their presumed line of differentiation.

Glioneuronal-mesenchymal tumour with malignant transformation.

We report a case of a 10-year-old girl with a tumour of the right temporoparietal region of the brain. The tumour consisted of three morphologically distinct portions: a well-differentiated one containing a mixture of a ganglioglioma with adipocytic-like cells and focal chondroid metaplasia, a separate island with neurocytic differentiation, and the malignant one, which exhibited an organoid pattern (trabecular and festooned) of primitive neuroectodemal tumour (PNET). We hypothesize that the latter component originated from the multicomponental glioneuronal tumour with mesenchymal differentiation and thus that lesion constituted an unusual example of malignant transformation of low-grade glioneuronal neoplasm.

[Mesenchymal tumors of the digestive tract, immunohistochemistry contribution]. / Les tumeurs mésenchymateuses du tube digestif, apport de l'immunohistochimie.

UNLABELLED: Mesenchymal tumors of the digestive tract are rare and display variable morphological appearances. Thanks to immunohistochemistry and molecular biology, these tumors are now better classified and dominated by stromal tumors. AIMS: the aim of this article is to study morphological characteristics of mesenchymal tumors of the digestive tract and to insist on immunohistochemistry contribution to diagnosis, especially the c-Kit. MATERIALS AND METHODS: this is a retrospective study of 40 mesenchymal tumors of the digestive tract diagnosed before the event of c-Kit, from 1985 to 1999 in the pathology laboratory of F. Hached hospital in Sousse. Immunohistochemical studies were performed on these tumors with the following antibodies: c-Kit, CD34, smooth muscle actin and S-100 protein. RESULTS: after immunostaining, the tumors were reclassified as the following: 33 stromal tumors, 4 leiomyosarcomas, 1 leiomyoma, 1 schwannoma and 1 desmoid tumor. CONCLUSION: mesenchymal tumors of the digestive tract are dominated by stromal tumors. The latter are defined usually by a spindle cell proliferation, often expressing the c-Kit protein which must be used in all mesenchymal tumors of the digestive tract.

Trends in incidence and survival of mesenchymal neoplasm of the digestive tract within a defined population of northern Norway.

Population-based incidence and survival data for gastrointestinal stromal tumor (GIST) are sparse due to the fact that GIST is a rather novel entity both clinically and pathologically, and has not been registered as a separate entity in population-based cancer registries. The aim of the present study was to reclassify all mesenchymal tumors within a defined population of northern Norway over a time-span of 30 years with the purpose of estimating trends of incidence and survival. One hundred and forty-one patients with mesenchymal neoplasms of the digestive tract were identified: 102 as GISTs, 32 as leiomyomatous tumors, 4 as schwannomas, and 3 as fibromas. Incidence rates of GIST showed a significant increase over the whole period, which was not observed for the non-GIST cases. Analysis of GIST cases showed that cases with more than 5 mitoses per 50 high power fields had an increased expected mortality 4 times that of those with fewer mitoses, and the combination of mitotic count and size of tumor can be recommended for categorizing the tumors into different risk levels. The study confirms that GIST is by far the most frequent mesenchymal neoplasm of the digestive tract and that the incidence has increased over the last 30 years.

Prognostic factors in the so-called malignant mesenchymoma: a clinicopathological and immunohistochemical analysis.

The term "malignant mesenchymoma" (MM) has traditionally been applied to a group of malignant soft tissue tumors that are characterized by the presence of two or more different mesenchymal tissue components in the same neoplasm. Currently, sarcomas with multilineage differentiation fulfilling the criteria of MM tend to be diagnosed as specific sarcomas with heterologous differentiation (e.g., de-differentiated liposarcoma) rather than MM; however, some cases of these tumors are difficult to classify. The purpose of this study was to analyze the clinicopathological and immunohistochemical features of these unclassifiable tumors, the so-called MM, and to determine whether some parameters are a useful adjunct for the classification of these tumors from the viewpoint of clinical outcome. Twelve cases of so-called MM were investigated retrospectively. The patients (six male, six female) ranged in age from 6 to 71 years (mean 48 years). Tumor size ranged from 3 to 20 cm (mean 13 cm). Tumor locations included the retroperitoneum (five cases), abdominal wall (two), thigh (two), forearm (one), lung (one), and parotid gland (one). The differentiated mesenchymal components were rhabdomyosarcomatous (RMS) (six cases), liposarcomatous (five), chondrosarcomatous (five), osteosarcomatous (five), or leiomyosarcomatous (four). Follow-up in all cases (range 4-129 months; mean 36 months) showed a 67% local recurrence rate, a 33% metastatic rate, and a 50% disease-related mortality. The patients who were under 40 years of age or who had an RMS component showed significantly worse survival than did patients in the other groups. The other mesenchymal components showed no significant correlation with survival. The immunophenotypes of p53 and mdm2 were almost identical between the two mesenchymal components in each case; however, there was no significant correlation between either of these immunophenotypes and the clinical outcome. None of the other factors (gender, tumor site, tumor size, or MIB-1-labeling index) was found to be a statistically significant prognostic indicator. In conclusion, a patient age under 40 years and the presence of an RMS component appear to be poor prognostic indicators of survival in patients with so-called MM, and to be a useful adjunct for the classification of these tumors.

[Current classification of gastrointestinal stromal tumors]. / Aktuelle Klassifikation des gastrointestinalen Stromatumors.

Gastrointestinal mesenchymal tumors traditionally have been designated as smooth muscle tumors. However, with increasingly accurate analytic tools most investigators were unable to demonstrate true myogenic differentiation. Diagnostic criteria and grading vary among different studies and the biological behavior of these gastrointestinal stromal tumors (GIST) is difficult to predict. In this manuscript the recent concept of GIST is reviewed, including a suggestion for tumor classification. Furthermore, MIB-1 and p53 immunohistochemistry and myogenic differentiation were evaluated as potential prognostic factors. Diagnosis requires the use of immunohistochemistry. Classification as GIST seems appropriate, since only few tumors show complete myogenic differentiation. Besides a tumor size over 5 cm, mitotic rate still seems to be the best predictor of treatment failure in tumors that are resected with a rim of uninvolved tissue. MIB-1 proliferation index above 4% and p53 positivity indicate a more aggressive course.

"Mesenchymal tumor" or "decidual-like reaction"?

For more than 40 yr, an unusual urinary bladder lesion has been known to occur in certain strains of mice, but no consensus has been obtained regarding its etiology, pathogenesis, biology, or classification. The lesion was first assumed to be epithelial and non-neoplastic, then it was called a smooth muscle cell tumor or leiomyosarcoma because of ultrastructural characteristics for smooth muscle cells. Later, the nonspecific term "mesenchymal tumor" was introduced due to histomorphologic differences from all smooth muscle tumors known. Recently, a proposal was made to name it "decidual-like reaction" because of the histomorphologic similarity to the rare spontaneous decidual reaction in the uterus of aging mice. Both lesions are characterized by spindle and large pleomorphic epithelioid cells with large bizarre nuclei; these characteristics mimic anaplasia of malignant tumors and led pathologists to assume a neoplastic nature. The decidual hypothesis is supported by the regular presence of nuclear progesterone receptors, the occasional occurrence of eosinophilic cytoplasmic granules, the rare finding of cells morphologically resembling granulated metrial gland cells (all also observed in the uterine decidual reaction), and the reproducibility through long-term feeding of combinations of estrogens and progestogens. It appears that the new decidual hypothesis can explain many detailed facets of the lesion, with the exception of the reported smooth muscle cell characteristics. The controversy of "mesenchymal tumor versus decidual-like reaction" should be resolved soon, not only as a scientific issue, but also because of consequences for risk assessment.

Somatostatin and vasoactive intestinal peptide receptors in human mesenchymal tumors: in vitro identification.

Somatostatin and vasoactive intestinal peptide (VIP) have been shown to be of diagnostic and therapeutic interest in several types of human epithelial tumors expressing the respective receptor. The present study evaluates the presence of somatostatin and VIP receptors in 64 primary or metastatic human mesenchymal tumors. In vitro receptor autoradiography on cryostat sections was performed using 125I-labeled [Tyr3]-octreotide as well as 125I-labeled [Leu8,D-Trp22,Try25]-somatostatin-28 as radioligands for somatostatin receptors and 125I-labeled VIP as radioligand for VIP receptors. Somatostatin receptors were identified in bone and vascular/perivascular tumors (3 of 3 osteosarcomas, 1 of 1 giant cell tumor, 2 of 2 angiosarcomas, and 4 of 4 hemangiopericytomas), in 2 of 2 synovial sarcomas, in 2 of 5 histiocytomas, and in several muscle cell tumors (1 of 2 leiomyomas, 2 of 4 leiomyosarcomas, and 3 of 5 rhabdomyosarcomas) but were absent in 4 liposarcomas, 3 mesotheliomas, 3 chondrosarcomas, 10 Ewing sarcomas, 11 schwannomas, and 5 Wilms' tumors. VIP receptors were identified in 3 of 3 differentiated liposarcomas, 2 of 2 angiosarcomas, 4 of 4 hemangiopericytomas, 2 of 2 synovial sarcomas, 3 of 3 mesotheliomas, 5 of 5 Wilms tumors, as well as in 2 of 5 histiocytomas, 1 of 2 leiomyomas, 2 of 4 leiomyosarcomas, 3 of 3 intermediately differentiated rhabdomyosarcomas, and 1 of 3 osteosarcomas but not in chondrosarcomas, Ewing sarcomas, schwannomas, or undifferentiated rhabdomyosarcomas. The receptors were located on neoplastic cells. The somatostatin receptors were of high affinity and of high specificity for biologically active somatostatin analogues with high affinity for somatostatin-14 and somatostatin-28 as well as for octreotide, thus representing the sst2 subtype; in a few cases of tumors having somatostatin receptors with low affinity for octreotide, in situ hybridization techniques identified preferentially sst1 mRNA. These data suggest that human mesenchymal tumors may be targets for somatostatin and/or VIP receptor in vivo imaging; they may also be potential targets for somatostatin or VIP analogue therapy.

[Classification of ovarian tumors based on embryogenesis]. / Classification des tumeurs de l'ovaire basée sur l'embryogenèse.

This paper studies gonadal differentiation into the ovary from the earliest interaction between germ cells and somatic cells in the developing urogenital ridge up to the formation of primordial follicles. Granulosa cells appear to be derived from the breaking down of the cordlike arrangement of epithelial cells resulting from proliferation of surface coelomic mesothelium. Thecal cells arise from mesenchymal progenitors cells in the ovarian stroma. Based on the findings of embryology and biology, the authors then propose a classification of ovarian tumors by rearranging the WHO classification.

Uncommon mesenchymal tumors of the liver. Light microscopy, ultrastructure, immunohistochemistry and literature review.

This report presents the gross morphology, cytological, histological, ultrastructural and immunohistochemical features of two angiomyelolipomas of the liver. Diagnosis and classification of these tumors is difficult. There is no immunohistochemical and ultrastructural confirmation for Ito-cell pathogenesis of hepatic angiomyelolipomas.

Immunohistochemistry as a diagnostic aid in the interpretation of unusual mesenchymal tumors of the uterus.

Sixty-three pure mesenchymal tumors of the uterus were studied to explore the value of immunostaining in the diagnosis of unusual mesenchymal tumors encountered in the uterus, some not reported previously. Each tumor was evaluated using a panel of immunostains including actin, desmin, vimentin, S-100 protein, and cytokeratin. The final classification, which incorporated the immunohistochemical findings, resulted in the identification of 33 relatively common pure mesenchymal tumors (13 benign and malignant endometrial stromal tumors and 20 benign and malignant smooth muscle tumors) and 30 uncommon tumors (five leiomyosarcomas with osteoclastic giant cells, two xanthomatous leiomyosarcomas, one melanotic schwannoma, one pure rhabdomyosarcoma, one neurofibroma, five plexiform tumorlets, and 15 combined smooth muscle-stromal tumors). The normal endometrial stroma, present in 14 cases, invariably showed a negative reaction for all antibodies. With rare exceptions, the pure endometrial stromal tumors displayed a negative immunoreaction for all antibodies utilized, while the pure smooth muscle tumors consistently showed a positive reaction for actin. Only the two tumors of neural origin (a neurofibroma and a melanotic schwannoma) reacted with S-100 protein. Immunostaining influenced most the final classification of neoplasms initially interpreted as uterine tumors with a sex-cord stromal pattern, endometrial stromal tumors that diverged from the classic lesions by having a spindle cell component, and intravascular leiomyomas with areas of compact proliferation of small round cells with prominent vascularity. All tumors in these three groups were reclassified as combined smooth muscle-stromal tumors following immunohistochemical studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Benign neoplasms of the oral cavity.

A wide variety of benign tumors present in the oral cavity. These tumors are for the most part rare and are classified by the tissue of origin. Although benign oral cavity tumors are not life-threatening, they can result in extensive loss of soft tissue and/or bone. Furthermore, many patients are subject to the threat of recurrence, multiple surgical procedures, and the possibility of malignant degeneration. Because many tumors vary little clinically, an adequate biopsy specimen must be obtained for diagnosis. Radiographs are, in general, nondiagnostic. Collaboration with an experienced pathologist is necessary to determine the tumor's probable clinical behavior. Therapy, which is dictated by tumor type, is almost always surgical.