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Relapse of monomorphic and pleomorphic Trypanosoma brucei infections in the mouse after chemotherapy.

Infections in mice were initiated with trypomastigotes from two lines of Trypanosoma brucei derived from the same primary isolated. Infections with one line were initiated by inoculation of metacyclic trypomastigotes from infected tsetse flies and the resulting infections were pleomorphic. The other line had been passaged 32 times in rodents and inoculation of bloodstream trypomastigotes gave rise to monomorphic infections. In both infections there were high levels of parasitaemia until death up to 4 weeks later if the infection was untreated. It was shown that after chemotherapy with 40 mg/kg diminazene aceturate (Berenil) relapses occurred in both types of infection after an aparasitaemic period of 2--3 weeks. Further, it was shown that 3 days after chemotherapy, brain tissue but neither spleen, liver nor blood was capable of transferring infection to normal recipient mice. There were two major differences in the response of the two infections to chemotherapy. First, treatment of the pleomorphic infection as soon as day 6 after infection resulted in a subsequent relapse while the monomorphic infection had to be at least 12 days old at the time of treatment before occurred. Second, following treatment of the pleomorphic, but not of the monomorphic infection there was an early transient recrudescence of low numbers of trypanosomes which were found to be non-infective to recipient mice. The early transient relapse was followed by a further aparasitaemic period and then the late continuous relapse characterised by large numbers of infective trypanosomes.

Amidines↗

A new cytogenetic subgroup in lipomas: loss of chromosome 16 material in spindle cell and pleomorphic lipomas.

Six spindle cell lipomas and two pleomorphic lipomas were analyzed cytogenetically. One spindle cell lipoma had a supernumerary ring chromosome as the sole anomaly. The other five spindle cell lipomas and both pleomorphic lipomas had hypodiploid stemlines with monosomy 16 or unbalanced aberrations leading to loss of 16q13-qter, a feature distinguishing these lipoma subtypes from other benign and borderline adipose tissue tumor histotypes. unbalanced aberrations of chromosomes 13 and 10 were found in five and three cases respectively; 13q12 was lost in all of these cases, whereas there was no common deleted segment in chromosome 10. No aberrations involving 12q13-15, which are frequent in typical lipomas, were found. Both pleomorphic lipomas, but none of the spindle cell lipomas, had hypotetraploid sidelines, multiple nonclonal aberrations, and telomeric associations. The present findings reveal a new cytogenetic/histopathological association in adipose tissue tumors.

Aged↗

Mixed pleomorphic-osteoclast-like tumor of the pancreas. Light microscopical, immunohistochemical, and molecular biological studies.

The morphological, immunohistochemical, and molecular biological features of a case of giant cell tumor of the pancreas are described. This neoplasm showed mononuclear and multinucleated tumor giant cells as well as numerous osteoclast-like cells with multiple foci of osteoid-osseous metaplasia. The pleomorphic and osteoclastic giant cells displayed extensive homologies in their immunohistochemical profiles. Neither the pleomorphic nor osteoclast-like portion of the tumor showed neither c-Ki-ras nor p53 mutation and did not express the mutated p53 protein. The results suggest that the pleomorphic and osteoclast-like components are histogenetically related and that this rare neoplasm originates from a precursor cell capable of differentiating along divergent cell type.

Aged↗

Primary pleomorphic liposarcoma of bone: MRI findings and review of the literature.

Primary liposarcoma of bone is exceedingly rare. We report a case of primary pleomorphic liposarcoma in the humerus of a 38-year-old female. Radiographs demonstrated an expansile and osteolytic lesion extending from the head to the proximal part of the shaft in the right humerus. MR study showed a defined lesion in the humerus. The lesion had an iso-signal intensity and partial high-intensity lesion on T1-weighted images and a heterogeneous high signal intensity on T2-weighted images. Wide resection and proximal humeral endoprosthesis replacement were performed. Final pathological diagnosis of the lesion was pleomorphic liposarcoma. This is the second reported case of pleomorphic liposarcoma of the bone, and the first case presenting MRI findings for liposarcoma of bone.

Adult↗

High molecular mass agarose matrix supports growth of bloodstream forms of pleomorphic Trypanosoma brucei strains in axenic culture.

Primary axenic culture of Trypanosoma brucei bloodstream forms almost invariably requires a period of culture adaptation with cell death and clonal selection. This has been particularly difficult and in many cases unsuccessful for natural pleomorphic strains, which are characterized by their ability to differentiate from replicating long slender bloodstream forms into short stumpy forms. Here we show that a representative set of pleomorphic T. brucei strains can be cultured in vitro on agarose plates without any previous adaptation period and selection. The slender morphology was retained and the growth rate was identical to the growth rate in vivo. Long term in vitro culture for 3 months with this method did not affect the ability of the AnTat 1.1 strain to give rise to pleomorphic infections in mice. Stumpy populations emanating from these infections transformed rapidly and synchronously into dividing procyclic forms when triggered with cis-aconitate and a temperature shift. The growth supporting activity of agarose plates could be traced to high molecular mass polymeric agarose; beta-agarase digestion destroyed the activity. Membrane chamber experiments show that direct physical contact of trypanosomes with the agarose matrix is essential. In the absence of high molecular mass agarose, the cell division process is grossly impaired. We suggest that agarose mimics an interaction of trypanosomes with the host's extracellular matrix. Applications of the culture method are discussed.

Animals↗

Incidence and significance of pleomorphism in patients with postmyocardial infarction ventricular tachycardia. Acute and long-term outcome of radiofrequency catheter ablation.

AIMS: The prognostic significance of multiple ventricular tachycardia (VT) morphologies, whether spontaneous or induced, was investigated in patients who underwent radiofrequency catheter ablation (RFCA) for postinfarction ventricular tachycardia. METHODS AND RESULTS: We studied 137 patients with postinfarction ventricular tachycardia. Catheter ablation of all induced ventricular tachycardias was attempted. A single ventricular tachycardia morphology was documented in 102/137 patients (MONO group); 35 patients had spontaneous pleomorphism (PLEO group). Multiple VT morphologies were induced in 58/102 (57%) MONO patients and in all PLEO patients. A higher rate of arrhythmia suppression was obtained in MONO as compared to PLEO patients (162/212 [76%] vs. 43/110 [39%]). Clinical presentation (VT pleomorphism) (OR: 0.22, CI: 0.08-0.62) and the induced VT cycle (mean PLEO/MONO: 338/385 ms, OR: 1.06) were independent predictors of acute RFCA success. Among MONO patients, the procedure was successful in 75% of the patients with a single induced ventricular tachycardia compared to 64% of those with multiple tachycardias. The acute success rate was lower in PLEO patients (23%). PLEO patients had a significantly higher 3- and 5-year arrhythmia recurrence rate than MONO patients. RFCA acute success was the only independent predictor of long-term outcome in multivariate analysis. CONCLUSIONS: Spontaneous, but not induced, VT pleomorphism in patients with prior myocardial infarction adversely affects the acute and long-term success rate of RFCA.

Aged↗

Nuclear beta-catenin correlates with cyclin D1 expression in spindle and pleomorphic sarcomas but not in synovial sarcoma.

Nuclear beta-catenin staining in soft tissue sarcomas (STSs) has been shown to correlate with tumor progression as assessed by proliferative activity or poor prognosis. Frequent activation of Wnt signaling pathway has been also shown in synovial sarcoma (SS), suggesting a specific role of this pathway in SS. We examined roles of nuclear beta-catenin staining within soft tissue sarcomas. Immunohistochemical detection of nuclear beta-catenin accumulation correlated with cyclin D1 overexpression in spindle cell and pleomorphic sarcomas (P = .037), and the expression of these proteins evenly distributed throughout each section. In some cases, strong beta-catenin nuclear staining was observed in highly pleomorphic and mitotic cells. Furthermore, tumors with nuclear beta-catenin accumulation showed statistically significant increasing cyclin D1 mRNA expression level compared with those without (P = .023). Cyclin D1 mRNA expression levels were statistically higher in tumors with cyclin D1 overexpression than in tumors without (P = .037), suggesting that cyclin D1 overexpression is due to transcriptional activation. However, these correlations could not be detected in SS. In biphasic SS, beta-catenin nuclear staining was observed in spindle cells, whereas cyclin D1 nuclear staining was seen in glandular areas where beta-catenin kept membranous expression. Mutations in exon 3 of the beta-catenin gene and in the mutation cluster region of adenomatous polyposis coli gene were absent in this series of cases. Thus, cyclin D1 could be considered as one of the targets of the nuclear beta-catenin in spindle cell and pleomorphic sarcomas. A possible association between beta-catenin accumulation and spindle cell morphogenesis may exist in SS.

Cell Nucleus↗

Recurrent pleomorphic adenoma of the parotid gland: long-term outcome of patients treated with radiation therapy.

PURPOSE: To evaluate the role of radiation therapy in the management of recurrent pleomorphic adenoma of the parotid gland. METHODS AND MATERIALS: Between 1960 and 2004, 34 patients were treated with postoperative radiation therapy for recurrent pleomorphic adenoma of the parotid gland to a median dose of 5000 cGy (range, 4,500-6,000 cGy). Median age was 48 years (range, 24-72 years). Gross total resection at the time of surgery before radiation was achieved in 30 patients (88%), and histologic analysis demonstrated multifocal disease in 16 patients (47%). Radiation was delivered for a first, second, third, fourth, fifth, and sixth local recurrence in 24%, 21%, 24%, 24%, 6%, and 3% of patients, respectively. RESULTS: With a median follow-up of 17.4 years (range, 2.3-28.9 years), 2 patients had local recurrences at a median of 3.4 years after completion of radiation. The 20-year actuarial local control rate was 94%. One patient developed a second malignancy at approximately 14 years after completion of therapy. CONCLUSION: The use of postoperative radiation therapy leads to excellent long-term local control for the treatment of recurrent pleomorphic adenoma with acceptable late toxicity. Although the incidence of second malignancy was low in this population, continued follow-up is warranted.

Adenoma↗

Immunohistochemical study of pleomorphic adenoma of the nasal septum.

A rare case of pleomorphic adenoma of the nasal septum is reported. A 48-year-old man complaining of nasal obstruction and nasal bleeding was referred to our hospital for treatment of a left nasal tumor. The tumor, including the nasal septum, was resected by the modified Denker operation and lateral rhinotomy. The tumor was firm, parenchymatous, pedunculated, and 24 x 22 x 14 mm in size. Pathological examination revealed pleomorphic adenoma with slight cellular atypism. Immunohistochemical observations suggested that characterization of this tumor might be similar to pleomorphic adenoma of the parotid gland.

Biopsy↗

Simultaneous pleomorphic adenomas of the right parotid and ipsilateral submandibular glands.

A case of simultaneous pleomorphic adenomas of the right parotid and ipsilateral submandibular glands was reported. The patient was a 68-year-old woman who had a ten-year history of an otherwise asymptomatic non-enlarging mass in the parotid gland and a slowly enlarging mass in the submandibular gland. Microscopically, the parotid tumor consisted of predominant spindle-shaped cell proliferations with myxoid stroma in places. The submandibular gland tumor showed tubular and trabecular formations with stroma consisting of hyalinized fibrous connective tissues. Simultaneous pleomorphic adenomas in the salivary glands are so rare that only 23 cases can be found in the literature. Additionally, only five tumors occurring simultaneously in the parotid and submandibular glands are reported in the literature. Our case seems to be the sixth of simultaneous pleomorphic adenomas of the parotid and submandibular glands.

Adenoma↗

Hidradenomata of the external auditory meatus. (Review of the literature and report of a pleomorphic adenoma).

A case of hidradenoma of the external auditory meatus ('ceruminoma') is presented, with a review of the literature. The tumour has the appearances of a pleomorphic adenoma and is devoid of a capsule. It is suggested that the term hidradenoma be used for tumours of the ceruminous glands and that they be classified histologically as (1) adenoma, (2) pleomorphic adenoma, (3) adenoid cystic carcinoma and (4) adenocarcinoma. This classification aids treatment and prognosis. Attention is drawn to the high incidence of malignancy in hidradenomata of the external auditory meatus. The treatment of choice for pleomorphic adenomata is wide surgical excision with an adequate margin of normal skin. If there is doubt regarding complete removal, or a recurrence develops, a wider surgical excision is necessitated.

Adenoma, Sweat Gland↗

Pleomorphic rhabdomyosarcoma of the larynx. A case report and review of the literature.

A case of pleomorphic rhabdomyosarcoma of the larynx occurring in a 33-year-old male is reported. The clinical and histopathological aspects of this undoubtedly rare neoplasm are described. After a quick review of the most important classifications of rhabdomyosarcoma so far made, the authors suggest a division into two basic groups, i.e. pleomorphic and fetal rhabdomyosarcoma, while the botryoid sarcoma and the alveolar rhabdomyosarcoma should be considered only as two subgroups of fetal rhabdomyosarcoma. From a comprehensive review of world literature on the subject, the well-documented cases up to now described are only seven, including the authors. The present case is the third one after the instances of pleomorphic rhabdomyosarcoma reported by Filipo and Crifo (1964 and by Rodriquez and Ziskind (1970).

Adult↗

Pleomorphic primitive neuroectodermal tumor with glial and neuronal differentiation: clinical, pathological, cultural, and chromosomal analysis of a case.

This paper examines a case of pleomorphic primitive neuroectodermal tumor (PNET) with glial and neuronal differentiation in a 7-year-old girl who was clinicopathologically reported with immunohistochemical and chromosomal analysis. Clinically, a highly aggressive behavior leading to early recurrence with cerebrospinal fluid seedings was characteristic despite total removal and chemoradiation therapy. Pathologically, severe pleomorphism was noted and large ganglioid cells were predominant. Immunohistochemically, the expression of low-molecular neurofilament was recognized in the surgical specimens and increased in the recurrence. Coexpression of vimentin and neurofilament/GFAP was recognized in the culture. Chromosomal analysis showed near-diploidy, but different karyotype from that PNETs previously reported. These findings suggested that PNETs with pleomorphism and differentiation into both glial and neuronal lineages may show aggressiveness and require more aggressive therapy.

Brain Neoplasms↗

Primary purely intradermal pleomorphic liposarcoma.

INTRODUCTION: Pleomorphic liposarcoma (PLPS) is a high-grade pleomorphic sarcoma, containing multivacuolated lipoblasts, which usually develops during late adult life. It usually occurs in the deep soft tissues and uncommonly arises in the subcutis, the dermis representing an exceedingly rare site of occurrence. METHODS: We describe a case of PLPS arising in the dorsal aspect of the nose of a 75-year-old woman. Preoperative duration was 9 months. RESULTS: The lesion was intradermal well-circumscribed, dome-shaped, measuring 1.2 cm. It fulfilled the histologic criteria for inclusion in the PLPS category. The tumor cells focally expressed calretinin. A review of the literature yielded four cases documented, to which we add the present report. All the patients were adults with a mean age of 67 (range 39-95) years, and three of five cases arose on the scalp. Local recurrence occurred in one patient, but no distant metastases or disease-related deaths were observed. CONCLUSION: PLPS very rarely arises in the dermis. In spite of high-grade morphology, the intradermal tumor shows a relatively favorable prognosis. Diagnostic consideration includes pleomorphic lipoma, clear cell atypical fibroxanthoma, balloon cell melanoma, and metastatic clear cell carcinoma of renal origin. Recognition of this distinctive and rare type of liposarcoma is essential to avoid under- or misdiagnosis and inappropriate treatment.

Aged↗

Pleomorphic rhabdomyosarcoma in adults: a clinicopathologic study of 38 cases with emphasis on morphologic variants and recent skeletal muscle-specific markers.

Pleomorphic rhabdomyosarcoma (PRMS) is a rare and controversial tumor of skeletal muscle phenotype. Diagnostic criteria for PRMS by combined histology and currently available immunohistochemistry have not been clearly defined. We report 38 pleomorphic rhabdomyosarcomas in adults, explore morphologic variants, and discuss our experience with both specific and nonspecific skeletal muscle markers in these tumors. Clinical data, morphology, and immunohistochemistry were reviewed. Electron microscopy was performed. Of 38 cases, there were 28 males and 10 females. Patient ages ranged from 21 to 81 years (median = 54 y; mean = 51 y). Tumors were located in the lower extremity (n = 18), abdomen/retroperitoneum (n = 6), chest/abdominal wall (n = 5), spermatic cord/testes (n = 4), upper extremity (n = 3), and one each in the mouth and orbit. Tumor sizes ranged from 1.5 to 15.0 cm (mean = 7.3 cm; median = 6.8 cm). The cases were divided into three variants, each with large, atypical, pleomorphic polygonal rhabdomyoblasts (PRMB) with abundant eosinophilic cytoplasm in varying numbers and different morphologic backgrounds of round or spindled rhabdomyoblasts (RMB). 1. Classic PRMS: Predominantly atypical PRMB in sheets (n = 8). 2. Round cell PRMS: Clusters of PRMB throughout the tumor with a background of slightly atypical, medium-sized, round, blue RMB (n = 13). 3. Spindle cell PRMS: Scattered PRMB in a predominance of atypical spindled RMB arranged in a storiform growth pattern (n = 17). Immunohistochemistry revealed the following: myoglobin (37/38), MyoD1 (19/36), skeletal muscle myogenin (myf4; 19/34), fast skeletal muscle myosin (4/5), desmin (36/38), muscle-specific actin (MSA; 25/35), smooth muscle actin (SMA; 15/33), and muscle specific myogenin (myf3; 25/35). Immunohistochemistry was supportive of skeletal muscle differentiation with at least one positive skeletal muscle-specific marker (myoglobin, MyoD1, fast skeletal muscle myosin, or myf4). In addition, all cases had some positivity for nonspecific muscle markers (desmin, MSA, SMA, myf3). Electron microscopy (EM), performed on eight selected cases from all three morphologic groups, demonstrated definitive skeletal muscle differentiation in all cases. Follow-up, available on 30 (79%) cases, revealed that 70% of patients died of disease (mean 20 months, range 1 month-108 months), 3% were alive with disease at 12 months (n = 1); and 27% had no evidence of disease (mean, 83 mo; range, 18 to 108 mo). PRMS, a tumor of predominantly middle-aged adult males in the lower extremity, can be diagnosed by the morphologic presence of scattered PRMB with immunohistochemical evidence of at least one skeletal muscle-specific marker. There are three morphologic variants of PRMS. The appropriate diagnosis of PRMS is significant as it is a high-grade sarcoma, with an aggressive clinical course.

Actins↗

Pleomorphic fibroma of the skin, a form of sclerotic fibroma: an immunohistochemical study.

We report a new case of pleomorphic fibroma of the skin arising on the face. The lesion was polypoid and fibrous, located on the dermis, and formed by coarse collagen bundles with sparse cells. It was also characterized by the presence of cellular atypia and pleomorphism without mitosis. Immunohistochemistry showed staining for vimentin and actin and negativity for S-100, CD34, CD68, alpha-1-antichymotrypsin and alpha-1-antitrypsin antigens, supporting a myofibroblastic origin. A few isolated cells also showed granular cytoplasmic detection of factor XIIIa. Although the disorder has been previously considered to be a tumour of preferential localization on the trunk or extremities, this does not always hold true as four of the 14 reported cases arose on the head. Pleomorphic fibroma is a benign condition and is we believe a variant of sclerotic fibroma.

Facial Neoplasms↗

Pleomorphic adenomas of the parotid express different mesenchymal phenotypes: demonstration of matrix gene expression products characteristic of the fibroblastic and chondrocytic cell lineages.

AIMS: Pleomorphic adenomas of the salivary glands are characterized by their high tissue diversity. Many studies have explored the derivation and differentiation of the neoplastic cells. We investigated the composition of the collagenous extracellular tumour matrix and could show a specific biochemical composition pattern in the different tumour areas. METHODS AND RESULTS: In epithelially differentiated acinar and ductal areas there was positive staining for basement membrane collagen type IV and no, or only scarce, staining for collagen types I, II, III, or VI. Solid areas mostly lacked any extracellular matrix. In areas with fibrous tissue-like appearance, the fibroblast-typical interstitial collagen types I, III and VI were seen. Chondroid areas showed abundantly the characteristic cartilage components, collagen type II and, pericellularly, type VI collagen. CONCLUSIONS: Our data show the presence of fibroblastic and chondrocytic cell differentiation in pleomorphic adenomas. Thus, they confirm that these neoplasms display, besides epithelial cell types, also real mesenchymal cell and tissue types. Differences in the abundance and the biochemical composition of the extracellular tumour matrix account largely for the morphological heterogeneity of pleomorphic adenomas of the salivary glands.

Adenoma↗

Myofibroblastic differentiation in malignant fibrous histiocytoma (pleomorphic myofibrosarcoma): a clinicopathological study.

AIMS: We compared the clinical and pathological features of pleomorphic malignant fibrous histiocytoma (MFH)-like soft tissue sarcomas with and without myofibroblastic differentiation on electron microscopy. METHODS AND RESULTS: Fifty-three soft tissue tumours designated as MFH by light and electron microscopy were reassessed. Eighteen were specifically diagnosed and excluded, and follow-up (FU) information obtained for 24 of the other 35 cases. Myofibroblastic ultrastructure was seen in 7/24 (29%). Seventeen of 24 (71%) lacked myofibroblasts on electron microscopy, which showed fibroblastic or undifferentiated cells. Histologically, all tumours but one had storiform-pleomorphic areas; one myofibroblastic neoplasm was fascicular and myxoid. No other morphological differences were seen. In seven myofibroblastic cases, smooth muscle in four cases and muscle-specific actin in two cases, desmin in three cases and S100 in one case were present. In 15 other tumours, smooth muscle in five cases and muscle-specific actin in one case, and desmin in one case were present; none of these cases expressed S100. CD34 was found in the myxoid areas of one myofibrosarcoma and 3/15 other tumours. Positivity for bcl-2 was seen only in non-myofibroblastic sarcomas (4/14). On follow-up (median 41 months), 2/7 (29%) myofibroblastic tumours recurred, 5/7 (71%) metastasized, and 3/7 (43%) patients died of disease. Among the non-myofibroblastic sarcomas, with a median follow-up of 47 months, 6/17 cases (35%) recurred, 10/17 (59%) metastasized, and 7/17 patients (41%) died of disease. CONCLUSIONS: Pleomorphic sarcomas with and without myofibroblastic differentiation on electron microscopy are clinically and histologically similar. The former display myoid immunohistochemical markers more frequently.

Adult↗