"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. (+info)
Epithelial-mesenchymal transition in proliferative vitreoretinopathy: intermediate filament protein expression in retinal pigment epithelial cells.
PURPOSE: To improve our understanding of how retinal pigment epithelial (RPE) cells behave in vivo and to establish similarities with dedifferentiation and adaptive events observed in RPE cells cultured under simulated intraocular pathologic conditions. At the same time, to examine the origin of epithelioid-shaped and fibroblast/fusiform-shaped cells in epiretinal membranes (ERM) from proliferative vitreoretinopathy (PVR). METHODS: Cells of ERM were studied by electron-immunocytochemical techniques, using simple, double, and triple immunostaining for cytokeratins (CK), vimentin (Vim), and glial fibrillary acidic protein (GFAP). Ultrastructural morphology analysis was also carried out. Adult human RPE cells were obtained and cultured with normal and pathologic vitreous from proliferative vitreoretinal disorders, subretinal fluid aspirates from retinal detachment, and normal human serum. Their cytoskeleton was fractionated at 7 (early cultures) and 24 (late cultures) days of culture, electrophoresed, immunoblotted for intermediate filament proteins, and quantified by densitometric analysis for each condition. Changes in phenotype characteristics were also evaluated. RESULTS: Epithelioid-shaped and fibroblast/fusiform-shaped cells, resembling RPE cells, expressed CK-Vim-GFAP simultaneously as intermediate filament proteins in their cytoskeleton. RPE cells in culture also expressed CK-Vim-GFAP and changed from an epithelial shape to a migratory fibroblast/fusiform-shaped phenotype in the presence of subretinal fluid aspirates and pathologic vitreous from proliferative intraocular disorders. In simulated cultures of proliferative intraocular disorders, cells decreased or retained their CK7, CK8, and CK18, retained Vim, and increased CK19 and GFAP, while their mesenchymal morphology became clearer over time. CONCLUSIONS: Studies of intermediate filament proteins in vivo suggest that dedifferentiation occurs in RPE cells in ERM. Dedifferentiated RPE cells may be responsible for epithelioid-like and fibroblast/fusiform-like cells. Furthermore, changes in intermediate filament protein levels were observed in RPE cells in simulated cultures of proliferative intraocular disorders. These changes were linked to cells acquiring a mesenchymal migratory, phenotype. Results indicate that the dedifferentiation of RPE cells occurs both in vivo and in vitro and that it can be explained as an epithelial-mesenchymal transition. (+info)
Establishment and characterization of a new continuous cell line from Lutzomyia longipalpis (Diptera: psychodidae) and its susceptibility to infections with arboviruses and Leishmania chagasi.
Embryonic tissue explants of the sand fly Lutzomyia longipalpis (Lutz & Neiva 1912) the main vector of Leishmania chagasi (Cunha and Chagas), were used to obtain a continuous cell line (Lulo). The tissues were seeded in MM/VP12 medium and these were incubated at 28 masculineC. The first subculture was obtained 45 days after explanting and 96 passages have been made to date. Lulo is composed of epithelioid cells, showed a 0.04 generations/hour exponential growth rate and population doubling time at 24.7 h. The cell line isoenzymatic profiles were determined by using PGI, PGM, MPI and 6-PGDH systems, coinciding with patterns obtained from the same species and colony's pupae and adults. The species karyotype characteristics were recognized (2n = 8), in which pair 1 is subtelocentric and pairs 2, 3 and 4 are metacentric. Lulo was free from bacterial, fungal, mycoplasmic and viral infection. Susceptibility to five arbovirus was determined, the same as Lulo interaction with Leishmania promastigotes. (+info)
Sarcoid reaction in primary tumor of bronchogenic large cell carcinoma accompanied with massive necrosis.
A 49-year-old woman consulted our hospital for evaluation of a tumor with cavitation in the S6 segment of the right lung. She was given a diagnosis of pulmonary tuberculoma because percutaneous needle aspiration cytology revealed epithelioid cells with a background of necrosis. However, a diagnosis of large cell carcinoma with central necrosis (p-T2NOM0) was established by thoracoscopic lung biopsy six months later. Pathological findings of surgical resection specimens showed that epithelioid cell granulomas adjacent to the neoplasm had a sarcoid reaction and the necrosis was related to the rapidly growing tumor because there was no clinical evidence of systemic sarcoidosis and pulmonary mycobacterial or fungal infection. This is the first report in which sarcoid reactions were recognized in a primary large cell carcinoma. (+info)
Abdominopelvic sarcoma of perivascular epithelioid cells. Report of four cases in young women, one with tuberous sclerosis.
The perivascular epithelioid cell has been proposed to be the unifying proliferating cell type in a number of lesions such as angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumor and renal capsuloma. With the exception of rare examples of angiomyolipoma, they are non-metastasizing. We report four examples of a new member of this family of perivascular epithelioid cell neoplasms that occur in abdominopelvic location and show metastatic properties. The patients, all women, were aged 19 to 41 years (mean, 32), and presented with a tumor mass involving the serosa of the ileum, uterus or pelvic cavity. Morphologically, the tumors were composed of sheets of large polygonal cells with glycogen-rich clear or eosinophilic cytoplasm and moderately pleomorphic nuclei, traversed by a delicate vasculature, mimicking clear cell carcinoma. There were areas of coagulative necrosis and occasional mitotic figures. Intracytoplasmic brown pigment was present in two cases. Spindly cells, smooth muscle and fat were absent. Lymphovascular invasion was present in all, lymph node metastasis was documented in two and metastasis to the ovary was present in one case. Two patients developed widespread metastatic disease after 10 and 28 months from diagnosis. One patient showed the clinical signs of tuberous sclerosis. In spite of the epithelial-like appearance, the tumor cells were negative for epithelial markers but were strongly positive with the melanogenesis-related marker HMB45. Another melanogenesis marker (MART-1) was positive in two cases. Other markers including S-100 protein, vimentin, muscle-specific actin, desmin and chromogranin A were negative. Thus, these tumors are not readily classifiable in the existing schema of known entities, and show overlapping morpho-phenotypic features of clear cell "sugar" tumor of the lung and epithelioid angiomyolipoma. We consider them as sarcomas composed of a pure population of uncommitted perivascular epithelioid cell, that lack modulation toward smooth muscle or adipose cells. (+info)
Primary extrapulmonary sugar tumor (PEST): a report of four cases.
The cell of origin and direction of differentiation of the clear cell tumor of the lung (the so-called sugar tumor) remains enigmatic. Recognition of HMB-45 immunoreactivity and identification of melanosomes have suggested a relationship to angiomyolipoma of kidney or liver and lymphangiomyoma. This has given rise to the concept that clear cell tumors are neoplasms of so-called perivascular epithelioid cells--PEComas. Herein we report the existence of four similar tumors occurring in extrapulmonary sites, one of which had malignant features. The three benign tumors occurred in females ages 9, 20, and 40 years; two were located in the rectum and one in the vulva. The malignant tumor occurred in the inter-atrial cardiac septum of a 29-year-old man. Common histologic features were a richly vascular organoid architecture, tumor cells with clear to pale eosinophilic cytoplasm, abundant glycogen, and immunoreactivity for HMB 45, but not S100, multiple keratin, neuroendocrine, or muscle markers. Benign tumors demonstrated low mitotic activity, no necrosis, and good circumscription; the malignant tumor showed considerable mitotic activity, necrosis, and an infiltrative growth pattern. Ultrastructurally, glycogen was present, mitochondria were abundant, and membrane-bound lamellated bodies consistent with premelanosomes were present in two cases, and equivocal in one. Because these tumors have light microscopic, immunohistochemical, and electron microscopic features similar to pulmonary sugar tumors, we propose the name primary extrapulmonary sugar tumor (PEST) for them. Although most PEST's are probably benign, malignant forms appear to exist. These cases further support the concept of a family of systemic HMB-45 positive tumors that include sugar tumors, angiomyolipoma of kidney or liver, lymphangiomyomas, and clear-cell myomelanocytic tumors of the falciform ligament/ligamentum teres. (+info)
Proximal-type epithelioid sarcoma: a clinicopathologic study of 20 cases.
We studied the clinicopathologic and immunohistochemical features of 20 cases of proximal-type epithelioid sarcoma to identify prognostic factors. The 20 patients ranged in age from 13 to 80 years (mean, 40 y); 12 patients were male and 8 were female. The tumors presented as deep soft-tissue or subcutaneous masses on the inguinal region in five, the thigh in four, the vulva in three, the axilla in three, and one each in the flank, chest wall, back, hip and perineum. The tumors ranged from 2 to 16 cm at their greatest diameter (mean: 7.8 cm). Histologically, 12 tumors (60%) were classified as the large-cell subtype, characterized by sheets of large cells with prominent nucleoli resembling poorly differentiated carcinoma, and a frequent rhabdoid phenotype, six (30%) were classified as the conventional subtype, and two (10%) as the angiomatoid subtype. The numbers of tumors exhibiting immunoreactivity for various markers were: vimentin (20 cytokeratin (20 [100%]); epithelial membrane antigen (17 [85%]); CD34 (9 [45%]); CD99 (5 [25%]); muscle markers, either desmin or alpha-smooth muscle actin (3 [15%]), other markers such as S-100 protein, neurofilament, neuron-specific enolase, synaptophysin and CD56 (12 [60%]); and p53 (16 [80%]). Fourteen lesions (70%) exhibited an MIB-1 index of 30% or more and, by a system of histologic grading using the MIB-1 score, 16 tumors (80%) were classified as high-grade (Grade 3). Thirteen patients (65%) developed local recurrence and 15 (75%) had metastases, primarily to the lymph nodes. At the last follow-up, 13 patients (65%) had died of their disease. A large tumor size and early metastasis were independently associated with a poor outcome. We conclude that proximal-type epithelioid sarcomas are rare, undifferentiated soft-tissue sarcomas of adults, with epithelioid features and a frequent rhabdoid phenotype. These tumors, when arising in proximal locations, have a much worse prognosis than those arising in distal locations. (+info)
c-kit mutations in gastrointestinal stromal tumors occur preferentially in the spindle rather than in the epithelioid cell variant.
Gastrointestinal stromal tumors (GISTs) coexpress CD34 and the Kit tyrosine-kinase receptor (CD117). A subset of GISTs carry gain-of-function mutations of the c-kit proto-oncogene in its juxtamembrane domain. The relationship between the mutational status and histological as well as immunohistochemical features has not been assessed in detail. 36 GISTs and 14 other gastrointestinal mesenchymal tumors were investigated for their morphology and immunophenotype as well as for the presence of c-kit mutations. DNA was extracted from formalin-fixed, paraffin-embedded tissue. Exons 9, 11, 13, and 17 of c-kit were analyzed by SSCP. Bands with altered mobility were excised, reamplified, and sequenced. C-kit mutations in Exon 11 encoding the juxtamembrane domain were identified in 19 cases (52.8%), with deletions in 12 cases, insertions in 3 cases (2 of these as duplications), and point mutations in 4 cases. The mutations clustered between Codons 553 and 561, pinpointing the critical region for deregulated Kit receptor activation. In both Exons 9 and 13, single mutations could be identified, whereas no mutations were found in Exon 17. There were c-kit mutations in 66.6% of benign GISTs (14/21), 83.3% of the malignant (5/6), and 40% of the cases of intermediate malignancy (2/5). A low frequency of mutations in benign GISTs, as reported previously by other researchers, could not be observed in our panel. Interestingly, all GISTs with c-kit mutations displayed a spindle cell phenotype, whereas mutations were absent in all 7 tumors with an epithelioid component (P =.03). This finding suggests a relationship between c-kit mutation and histological subtype in GISTs. (+info)