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[Cutaneous mesenchymal neoplasms versus mesenchymal neoplasms of subcutaneous and deep soft tissue. Similarities and differences].

As in subcutaneous and deep soft tissues, cutaneous mesenchymal neoplasms are also relatively rare and characterized by a clinicopathological heterogeneity. There are striking differences in regard to the occurrence of different lines of differentiation of mesenchymal neoplasms in superficial and deep locations, and some distinct entities arise exclusively in the dermis. Superficially located mesenchymal neoplasms are characterized by a number of specific morphological features in comparison to deeper located lesions. Clinically important, dermal sarcomas of some lines of differentiation are associated with a favorable clinical prognosis, independent of the histological grading, which is important to know for the correct treatment of patients. In the following review similarities and distinguishing clinicopathological features of superficially and deeply located mesenchymal tumors are discussed.

Diagnosis, Differential↗

Ultrastructural characterization of pulmonary neoplasms. II. The role of electron microscopy in characterization of uncommon epithelial pulmonary neoplasms, metastatic neoplasms to and from lung, and other tumors, including mesenchymal neoplasms.

Ultrastructural analysis through better resolution adds significant information to the evaluation and classification of primary pulmonary neoplasms. Light microscopy is limited in the evaluation of lung neoplasms. In some cases the light microscopic appearance may be entirely misleading, whereas in others it is inconclusive. Immunocytochemistry provides information on cytoplasmic differentiation of various tumors and hence more data on their corresponding phenotypes. The data from immunocytochemistry without corresponding objective electron microscopic evaluation may be very difficult to interpret. Correlation of historical, gross, light, electron microscopic, and immunocytochemical data is essential for a final accurate diagnosis (fig. 20). Fine needle aspiration of pulmonary neoplasms is becoming very fashionable and a diagnosis, including type of neoplasm, is expected on the basis of examination of a limited number of cells which further emphasizes the importance of ultrastructural characterization in helping to establish an accurate diagnosis [63-69]. The current classification of pulmonary neoplasms may need to be modified in the near future to incorporate the newly created data [70-72]. At the present time, there appears to be, at least, a need for a 'double standard', as Sobin [73] has suggested, which would permit the evaluation of the biologic significance of the ultrastructural and immunocytochemical findings (as applied to classification of neoplasms) in an effort to derive meaningful clinicopathologic correlations. Figure 20 emphasizes the additive role which should be played by the various diagnostic modalities to enable a morphologic assessment which would be an accurate predictor of biologic behavior. With an accurate assessment of biologic behavior, a more appropriate and rational approach for therapy is possible. There is also an important role for ultrastructural analysis in metastatic pleural and pulmonary neoplasms, primarily adenocarcinomas, as well as in the differential diagnosis of pulmonary neoplasms versus other tumors that may be similar in histological appearance. The role of ultrastructure in mesenchymal neoplasms is also crucial in defining specific neoplastic cell populations and in some cases in the differentiation from other non-mesenchymal tumors. It seems that routine electron microscopic examination of pulmonary neoplasms provides additional information that may be of great value in the management of patients and in understanding the differentiation, and perhaps histogenesis, of pulmonary neoplasms.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

Protein gene product 9.5 (PGP 9.5) is not a specific marker of neural and nerve sheath tumors: an immunohistochemical study of 95 mesenchymal neoplasms.

In non-neoplastic tissues, the expression of protein gene product 9.5 (PGP 9.5), a member of the ubiquitin hydrolase family of proteins, is confined to neural and neuroendocrine cells. Although it has been claimed that PGP 9.5 is a specific marker of neural and/or nerve sheath differentiation in human tumors, careful review of the literature suggests that relatively few nonneural or nerve sheath tumors have been studied. Prompted by our recent observation of a PGP 9.5-positive malignant fibrous histiocytoma, we undertook a study of PGP 9.5 expression in a large group of well-characterized mesenchymal neoplasms. Sections from 95 mesenchymal tumors were retrieved from our archives and immunostained for PGP 9.5 using standard avidin-biotin complex technique and heat-induced epitope retrieval. Scoring was as follows: negative, 1+ (<10-25% of cells), 2+ (25-50% of cells), and 3+ (>50% of cells). Normal nerves and fibrous tissue were internal positive and negative controls, respectively. Positive immunostaining was seen in 80/95 (84%) of cases. Positive results by tumor subtype were as follows: (1) nerve sheath tumors: malignant peripheral nerve sheath tumor (7/10), neurofibromas (10/10), and perineuriomas (3/3); (2) (Myo) fibroblastic tumors: malignant fibrous histiocytoma (18/20), low-grade fibromyxoid sarcomas (8/9), fibromatoses (7/7), and desmoplastic fibroblastomas (2/2); (3) vascular tumors: angiosarcomas (4/4), hemangioendotheliomas (3/5), and hemangiomas (3/4); and (4) other non-nerve sheath tumors: pleomorphic liposarcoma (4/4), dermatofibrosarcoma protuberans (2/5), rhabdomyosarcomas (2/2), synovial sarcomas (8/8), melanomas (1/2). All positive cases were 2-3+ except 6 malignant peripheral nerve sheath tumor, 1 neurofibroma, 3 malignant fibrous histiocytoma, 2 low-grade fibromyxoid sarcoma, and 1 dermatofibrosarcoma protuberans. Positive staining was seen in normal smooth muscle and germinal centers in addition to nerves. We conclude that in this, the largest study to date of PGP 9.5 expression in mesenchymal neoplasms, we have found strong (2-3+) expression in the vast majority of nonneural or nerve sheath neoplasms studied. Although PGP 9.5 is a sensitive neural/nerve sheath marker, it is essentially totally nonspecific for diagnostic purposes. It is possible that our findings reflect cross-reactivity of the 13C4 clone with epitopes present on other ubiquitin hydrolases. Alternatively, PGP 9.5 expression may be aberrantly up-regulated in a variety of mesenchymal neoplasms.

Biomarkers, Tumor↗

Undifferentiated mesenchymal neoplasm of the esophagus in a child: case report and comparison with gastrointestinal stromal tumor.

Mesenchymal neoplasms of the esophagus are relatively uncommon in adults and exceedingly rare in children. Childhood tumors consist almost exclusively of smooth muscle tumors (leiomyomas). We report a case of an undifferentiated mesenchymal neoplasm occurring in the distal esophagus of a 15-year-old boy which is not a gastrointestinal stromal tumor. To our knowledge, this is the first reported case of such a neoplasm occurring in the esophagus of either an adult or child.

Adolescent↗

Cytological features of epithelioid mesenchymal neoplasms: a study of 21 cases.

Epithelioid mesenchymal neoplasms (EMNs) are rare tumors that share cytological, histological, and immunohistochemical features with epithelial tumors. It is important to distinguish EMNs from epithelial tumors in cytology specimens due to their different clinical management and prognosis. The cytomorphological features of histologically confirmed EMN were reviewed. Twenty-one cytological specimens of EMN were evaluated and characterized by polygonal cells with moderate to abundant dense cytoplasm, prominent nucleoli, and pleomorphism. Additional findings included the presence of a distinct population of spindle cells, hemosiderin-containing cells, multinucleated cells, and granuloma-like structures in selected cases. Cytokeratin immunoreactivity was seen in two cases and was negative in one case. This study shows that the cytological features of EMNs and epithelial tumors overlap; nonetheless, some features are more helpful in suggesting EMN. A panel of immunocytochemical studies must include specific mesenchymal markers to avoid a misdiagnosis of carcinoma in cases of cytokeratin-positive EMN.

Adult↗

Diagnostic and biological implications of mel-CAM expression in mesenchymal neoplasms.

Mel-CAM (previously MUC18) is an integral membrane glycoprotein involved in heterophilic intercellular adhesions. Mel-CAM is expressed specifically in certain normal mesenchymal tissues, including smooth muscle, endothelium, and Schwann cells. As a member of the immunoglobulin supergene family of cell adhesion molecules (CAMs), Mel-CAM may play a pivotal role in the normal differentiation and functional activity of these tissues. To determine the distribution of Mel-CAM in mesenchymal neoplasms and to investigate its potential role as a factor in tumor progression, we evaluated a spectrum of mesenchymal neoplasms by immunohistochemistry using a Mel-CAM-specific polyclonal antibody on formalin-fixed tissues. Mel-CAM positivity was observed in 5 (100%) of 5 leiomyomas, 29 (91%) of 32 leiomyosarcomas, 5 (100%) of 5 hemangiomas, 5 (100%) of 5 angiosarcomas, 3 (100%) of 3 Kaposi's sarcomas, 8 (100%) of 8 schwannomas, 10 (100%) of 10 neurofibromas, 0 (0%) of 8 malignant peripheral nerve sheath tumors, 2 (15%) of 13 malignant fibrous histiocytomas, 0 (0%) of 8 fibrosarcomas, 0 (0%) of 7 synovial sarcomas, and 0 (0%) of 6 liposarcomas. These results show that Mel-CAM is expressed consistently in neoplasms of smooth muscle and vascular origin, and that immunostaining for Mel-CAM may serve as a useful adjunct in differentiating leiomyosarcomas, angiosarcomas, and Kaposi's sarcomas from other spindle cell neoplasms. Furthermore, the observation that Mel-CAM is expressed consistently in schwannomas and neurofibromas but not in malignant peripheral nerve sheath tumors implicates Mel-CAM as a potential modulator of malignant transformation in peripheral nerve tumors.

Antigens, CD↗

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.

Actins↗

Fibrous inflammatory polyps of the ileum and cecum: review of five cases with emphasis on differentiation from mesenchymal neoplasm.

Five case histories of patients with fibrous inflammatory polyps of the ileocecum are reported. Clinical impression in all five cases was that these tumefactions represented gastrointestinal malignancies. Gross pathologic examination revealed polypoid intramural growths ranging from 2.5 to 7.0 cm in greatest dimension. Transmural desmoplasia through the bowel wall into subserosal fat was initially thought to be indicative of neoplastic invasion. Microscopic evaluation revealed a fibroblastic and vascular proliferative process. Pseudosarcomatous changes were identified in cellular fibroblastic areas with plemorphism and mitotic activity. The manner of dissection among bundles of muscularis mucosae and muscularis propria suggests an inflammatory process as opposed to the pushing aside of whole large muscle bundles as seen in mesenchymal neoplasms arising in bowel wall. All five patients experienced survival of 6 to 17 years following surgery. These lesions are thought by us to represent localized exuberant polypoid granulation tissue proliferations which simulate mesenchymal neoplasm.

Cecum↗

Unusual dural and skull-based mesenchymal neoplasms: a report of four cases.

Dural and skull-base mesenchymal neoplasms other than meningiomas are rare. We report four such tumors, some of which are uncommon even in nonintracranial sites, in three adults and one child. The adult tumors consisted of a synovial sarcoma of the third ventricle region in a 19-year-old woman, a leiomyoma of the suprasellar region in a 57-year-old woman, and an Epstein-Barr virus (EBV)-associated smooth muscle tumor of the cavernous sinus in a 35-year-old woman with acquired immunodeficiency syndrome (AIDS). The pediatric tumor was an EBV-associated leiomyosarcoma of the left dural transverse sinus in a 14-year-old girl with common variable immunodeficiency syndrome. All tumors were thought to be primary in their dural or skull-base locations. The two EBV-associated smooth muscle tumors in immunocompromised patients expand the locations for EBV-associated smooth muscle tumors to dural and skull-base sites, the synovial sarcoma is unique to the intracranial space, and the sellar leiomyoma represents the third reported sellar smooth muscle tumor.

Acquired Immunodeficiency Syndrome↗

Distinctive dermal clear cell mesenchymal neoplasm: clinicopathologic analysis of five cases.

Dermal clear cell tumors are not common. This group of lesions is comprised primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and metastatic clear cell carcinomas. We report the clinicopathologic features of five cases of a novel dermal clear cell neoplasm that appears mesenchymal in nature. The affected patients included 3 men and 2 women ranging in age from 38 to 70 (median, 45 years). All the lesions occurred on the lower limb. Clinically described as smooth cutaneous nodules, size ranged from 0.5 to 2.5 cm in greatest dimension and the lesions were present from weeks to 5 years prior to excision. Situated in the reticular dermis, the tumors usually extended to involve the subcutis with sparing of the papillary dermis. The tumors were composed of large optically clear cells with vesicular nuclei. The lesions entrapped adnexal structures and thin dermal collagen fibers. Mitoses were rare (less than 1 per 25 hpf). A single case showed more pleomorphic nuclei as well as quite frequent mitoses and was considered of uncertain biologic potential. Immunohistochemistry revealed reactivity only for NKI-C3 (5/5 cases), CD68 (2/5 cases), and vimentin (2/3 cases); melanocytic, epithelial, and lymphoid markers were uniformly negative. All five lesions were locally excised; the more pleomorphic and mitotically active lesion was widely re-excised and given subsequent radiation therapy. In follow-up ranging from 1.5 to 11 years (median, 5.5 years), none of these lesions has recurred. These tumors appear to be mesenchymal in nature, but their precise line of differentiation is unknown. Recognition of these lesions is important to avoid confusion with better-known malignant neoplasms.

Adult↗

Lipoblastoma-like tumour of the vulva: report of three cases of a distinctive mesenchymal neoplasm of adipocytic differentiation.

AIMS: We sought to delineate and describe three cases of a distinctive mesenchymal neoplasm of the vulva showing adipocytic differentiation and affecting young patients. METHODS AND RESULTS: In three patients between 13 and 38 years of age, the vulvar tumours had well-circumscribed borders and ranged in size from 35 to 100 mm. Histologically, they were well circumscribed and lobulated. The lobules were separated by thin fibroconnective tissue septa and were composed of slender spindle cells showing slightly eosinophilic cytoplasm with indistinct boundaries, uniform nuclei with finely granular chromatin, and no nucleoli. The cells were embedded in a richly myxoid stroma. The background in all three tumours was a 'chicken-wire', capillary vascular network resembling that seen in myxoid liposarcomas. Two tumours had scattered signet-ring-type lipoblasts and the third a large number of such lipoblasts. Clusters of mature adipocytes were entrapped in the tumours. None had mitotic figures, necrosis, or pleomorphism. The neoplastic cells stained positively for vimentin and were negative for other immunohistochemical markers. Treatment for all three tumours was enucleation alone. After follow-up of 10 years, 7 years, and 1 year, all patients are well with no evidence of disease. CONCLUSIONS: The benign behaviour of these neoplasms militates against the diagnosis of liposarcoma. We believe these are benign lesions of adipocytic differentiation akin to infantile lipoblastomas.

Adipocytes↗

[Malignant mesenchymal neoplasms of the oromaxillofacial area. The diagnostic problems].

Oral and maxillo-facial mesenchymal malignant neoplasms are rare. They involve nosologic, diagnostic and therapeutic problems. Clinical cases of soft and bone tissue are reported. They share difficulties in clinical, roentgenographic and histopathological diagnosis and often the disagreement between the clinical evidence and the histopathological report. The rule of the immunohistochemistry for a correct characterization of mesenchymal malignant neoplasms and the necessity for correct and early diagnostic definition in order to plain the treatment are emphasized.

Adolescent↗

Induction of mesenchymal neoplasms by DMBA implantation in deep lingual submucosa of male albino rats.

45 male albino rats were used to study the effect of deep submucosal implantation of DMBA on lingual carcinogenesis. The results showed development of different mesenchymal neoplasms (fibroma, fibrosarcoma and leiomyosarcoma). So, this method of implantation could not be used as an ideal animal model for production of single known neoplasm as had been investigated by many investigators before.

9,10-Dimethyl-1,2-benzanthracene↗

Biological continuum of benign, atypical, and malignant mesenchymal neoplasms - does it exist?

The characterization of specific cytogenetic and molecular abnormalities in benign and malignant soft tissue tumours has increased our understanding and knowledge of the biology of these rare neoplasms in recent years and has led to the modification of a number of traditional classification schemes. Contrary to popular belief, it is reasonable to propose that there exists a molecular, genetic, and morphological continuum of benign, atypical, and malignant mesenchymal neoplasms. The identification of characteristic molecular changes in benign lipomas, lipomas with minimal atypia, and atypical lipomatous tumours, well-differentiated liposarcomas supports the hypothesis of a stepwise process in the pathogenesis of these neoplasms. Not only are these findings important for our understanding of the biology of soft tissue tumours, but they also may increase diagnostic and prognostic accuracy.

Disease Progression↗

[Mesenchymal neoplasms of the skin. (A normative study)].

On the basis of a retrospective study of a large bioptic material, a scheme for a histological classification of mesenchymal cutaneous neoplasms has been suggested. The scheme as proposed here has been discussed and compared with the elaborations of WHO (1,2) and those of AFIP (3,4).

Humans↗

Nephroblastoma in the rat: histology of a spontaneous tumor, identity with respect to renal mesenchymal neoplasms, and a review of previously recorded cases.

The histology of a spontaneously occurring neoplasm of the rat kidney conforming to a classification of nephroblastoma is described and compared with that of N-nitrosodimethylamine-induced renal mesenchymal tumors. This rat nephroblastoma was an encapsulated epitheloid neoplasm with a uniform histologic pattern. Clumps of densely crowded, hyperchromatic cells frequently associated with central, well-differentiated ducts were supported by a less cellular, interconnecting stroma of loose areolar or mature fibrous connective tissue. Neoplastic cells were organized into primitive, ill-defined tubular formations. The neoplastic cell component strongly resembled metanephrogenic blastema. In contrast, the renal mesenchymal tumor was nonencapsulated and consisted of a heterogeneous mixture of connective tissue elements including fibroblast-like spindle cells, smooth muscle, and embryonic mesenchyme that engulfed and sequestered preexisting renal tubules and glomeruli. The separate morphologic identities and apparently unrelated existence of rat nephroblastoma and renal mesenchymal tumor were stressed. The rat nephroblastoma morphologically resembled the malignant epithelial component of human Wilms' tumor, whereas rat renal mesenchymal tumor appeared to have counter-parts in the mesenchymal component of Wilms' tumor and in congenital mesoblastic nephroma (leiomyomatous hamartoma) of infancy. The histologic descriptions of previously recorded occurrences of spontaneous and experimentally induced rat neoplasma classified as nephroblastoma or its synonyms were reevaluated in comparison to the present case. In all but four instances, in which sufficient histologic detail was provided in previous reports, a consistent histologic pattern emerged for this neoplasm in the rat.

9,10-Dimethyl-1,2-benzanthracene↗

Hyalinized Uterine Mesenchymal Neoplasms with HMB-45-Positive Epithelioid Cells: Epithelioid Leiomyomas or Angiomyolipomas? Report of Four Cases.

We present 4 cases of uterine mesenchymal tumors that were located mostly in the myometrium in middle-aged women. Grossly the tumors vaguely resembled conventional leiomyomas. All tumors were extremely hyalinized. The tumor cells were remarkable because of their large size and epithelioid shape. They occurred singly or more often in variously sized clusters with pericellular clear spaces looking like a halo. The extracellular matrix often formed lacunae around the neoplastic cells. The lacunar type of growth was somewhat reminiscent of immature cartilage. In some places the cells lined up in vague cord-like structures. The epithelioid cells often grew within vessel walls and subendothelially, simulating angioinvasion. In 2 cases there were periodic acid-Schiff (PAS)-positive, needle-shaped crystalloids in the cytoplasm of the tumor cells. No atypias and no mitoses were found in any of the 4 tumors. Mucicarmine stain was negative in all cases. Immunohistochemically the tumor cells were negative for cytokeratins, synaptophysin, chromogranin, epithelial membrane antigen (EMA) S-100 protein, and inhibin. They were instead strongly positive for smooth muscle actin, desmin and HMB-45. All patients are disease free after a 1-4-year follow-up. Int J Surg Pathol 8(4):323-328, 2000

Journal Article↗

Pure mesenchymal neoplasms of the uterine corpus: selected problems.

The first part of this review includes a discussion of some issues in decision analysis as it applies to uterine mesenchymal tumors, as well as a discussion of some of the morphologic features and histochemical techniques that may be used to determine whether a mesenchymal tumor is demonstrating smooth muscle or endometrial stromal differentiation. Also included in the first part are caveats that the pathologist should observe before interpreting mesenchymal tumors of the uterus. The second part of the paper is devoted to morphologic diagnostic criteria and differential diagnosis.

Diagnosis, Differential↗