Unpredictable Biological Behavior Research Articles

Management of dermatofibrosarcoma protuberans with fibrosarcomatous transformation: an evidence‐based review of the literature

Fibrosarcomatous transformation represents a rare event in dermatofibrosarcoma protuberans (DFSP) with unpredictable biological behaviour. No guidelines for the adequate treatment of patients with this rare neoplasm have been published. Herein, we present a comprehensive review of the literature comprising 157 patients with transformed DFSP focussing on surgical and adjuvant treatment modalities for this tumour. In the cohort examined, local recurrence occurred in 36% of cases and was significantly lower in patients treated by wide excision with margins ≥2 cm when compared with those treated with local excision without defined margins (P = 0.01). Consistently, negative margin status was associated with a lower recurrence rate when compared with positive or unknown margin status (P = 0.01). Distant metastases were detected in 13% of patients, which is significantly higher when compared with ordinary dermatofibrosarcoma protuberans. Systemic dissemination was preceded by local recurrence in 81% of cases, and is therefore strongly associated with tumour recurrence (P ≤ 0.001). The present data confirm that wide excision with margins ≥ 2 cm represent the gold standard in the treatment of transformed dermatofibrosarcoma protuberans, and prevents recurrence as well as metastasis. When R0-resection is not feasible, adjuvant radiation should be considered for cases with incomplete resection or unknown surgical margins. Irresectable or metastatic transformed DFSP harbouring the COL1A1-PDGFB fusion gene should be treated with imatinib in the palliative setting or as an adjunctive treatment before surgery, although responses may be short-lasting.

Malignant Progression of a Pleomorphic Xanthoastrocytoma in a Child

Pleomorphic xanthoastrocytoma (PXA) is a recently recognized rare cerebral neoplasm that predominantly affects young patients. We report on the case of a 3-year-old boy who presented with a 2-week history of headaches and seizures. Radiological investigation revealed a lesion in the right parietal-occipital lobe. The lesion was excised and histology disclosed the presence of a PXA with anaplastic features. 1 year later follow-up magnetic resonance imaging (MRI) revealed tumor relapse. An MRI of the spine was also performed and demonstrated leptomeningeal dissemination. The patient underwent a second operation. Histology revealed that the presence of a malignant PXA with anaplastic features. The patient received radiotherapy and 9 months later on follow-up MRI a new tumor recurrence was noted. A third craniotomy was performed and the tumor removed. Histological examination revealed dedifferentiation to glioblastoma multiforme. The patient was referred to the oncology department and received chemotherapy with temozolamide. 8 months later the patient was stable without tumor recurrence. PXAs require close follow-up because of their unpredictable biological behaviour.

Fat-forming solitary fibrous tumour (lipomatous haemangiopericytoma) of the spine: case report and literature review

Solitary fibrous tumour (SFT) is a rare soft tissue tumour of uncertain histogenesis and unpredictable biological behaviour, which was first described in the pleura and subsequently in many extra-pleural locations. Fat-forming SFT is a sub-type of SFT and only a handful of cases have been reported in the literature. We present the clinical, radiological and histological features of a case of intraspinal fat-forming SFT, along with a literature review. This is the first known report of a fat-forming SFT in the spine.

Prognostic significance of proliferation markers and telomerase activity in gastrointestinal stromal tumors.

10078 Background: Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, represent a heterogeneous group of neoplasms with an unpredictable biological behavior ranging from benign to malignant. It is difficult to determinate their aggressive behavior despite known prognostic factors such as tumor size, mitotic activity and tumor location or mutation status of genes c-kit or PDGFRα. Molecular markers including mechanisms of proliferation (Ki67 and TPX2) or cellular senescence (reactivation of telomerase activity) may provide an additional information on biological behavior of these neoplasms. Methods: We measured Ki67 and TPX2 mRNA levels as proliferation markers and hTERT (human Telomerase Reverse Transcriptase) mRNA level as a marker of telomerase activity using absolute quantification real time RT PCR. Normalized levels of proliferation markers Ki67, TPX2 and hTERT (normalized to mRNA levels of ABL housekeeping gene) was correlated between the different groups of tumors such as GIST, leiomyoma and a group of tumors with aggressive and high proliferation status, and finally, between risk categories of GIST. Results: The group of patients with agrressive and high proliferate Burkitt lymphoma (n=19) expressed significantly higher levels of Ki67 (p<0.0001), TPX2 (p<0.0001) and telomerase subunit hTERT (p<0,0001) than a group of patients with GIST (n=89, 90 and 58 respectively) or leiomyoma (n=9, 9 and 4 respectively). Statistical correlation was also found in the levels TPX2 and high risk category of GIST, a subgroup of patients with high risk GIST (n=36) expressed significantly higher levels of TPX2 proliferation marker (p=0.0101) than patients in the group with very low (n=4), low (n=3) and intermediate risk (n=5). Conclusions: Molecular evaluation of telomerase activity and biological markers involved in proliferation of cells may define an increased risk of aggressive behavior and to help to predict prognosis of GISTs. Assessement of the expression of TPX2 proliferation marker may become a suitable tool to determine biological behavior of GISTs. Supported by VZ FNM MZO 00064203/6704. No significant financial relationships to disclose.

Imaging Appearance of Solitary Fibrous Tumor of the Abdominopelvic Cavity

The computed tomographic or magnetic resonance imaging appearance of solitary fibrous tumors of the abdominopelvic cavity has previously only been presented in the English literature as individual case reports. In this article, we present the cross-sectional imaging appearance of 5 such cases, all of which exhibited highly similar imaging features, including well-circumscribed margins, lack of invasion of adjacent structures, and avid enhancement. In view of these shared imaging features, it may be possible to suggest the diagnosis preoperatively. Given their unpredictable biologic behavior with infrequent reports of recurrent or metastatic disease, complete surgical excision and long-term follow-up for these lesions is recommended.

Solitary Fibrous Tumor Presenting as a Parapharyngeal Mass

AbstractSolitary fibrous tumors (SFT) rarely occur in the neck region and can be easily mistaken for more common tumors if the index of suspicion is not high. They are characterized by remarkable histologic variability. However, immunopositivity for CD34 and Bcl2 with immunonegativity for other markers aid in establishing the diagnosis. Distinction from the other common benign entities is essential, as SFT are tumors of low grade aggressiveness and unpredictable biologic behavior. Complete resection is the key feature determining outcome.

Inflammatory myofibroblastic tumors in childhood

Inflammatory myofibroblastic tumors (IMTs) are myofibroblastic lesions with unpredictable biologic behavior that occur at a young age. For this report, the authors investigated clinicopathologic features in a series of pediatric IMTs. The objective of the study was to identify morphologic or immunohistochemical prognostic markers and the possible pathogenic role of human herpes virus 8 (HHV-8). Twenty-six patients were observed over a period of 18 years. Clinical/histologic data were reviewed, and immunohistochemical/molecular studies were performed. Patients ages 8-216 months (median age, 60 months) presented with tumors of the lung-bronchus (8 patients), abdomen (17 patients), and thoracic wall (1 patient). Twenty-one patients underwent complete excision, and microscopic or macroscopic residual disease was present in 5 of those patients. Chemotherapy was received by 5 patients. After a median follow-up of 6.6 years, 24 patients were in complete remission, and 2 patients had died of disease. Local recurrences were observed in 6 patients (including 4 recurrences that occurred after a complete excision). Cytologic atypia, low inflammatory infiltrate, and a rich myxoid pattern were detected in patients who had recurrent disease or a poor prognosis. Anaplastic lymphoma kinase (ALK) was positive in 7 patients (including 2 patients with recurrent disease). No correlation between clusterin expression and prognosis was demonstrated. HHV-8 was identified in 1 pulmonary IMT. IMTs are locally aggressive lesions. In this series, the local recurrence rate was 23%, and the 5-year and 10-year event-free survival rates were 87.4% and 72.8%, respectively. The results indicated that the treatment of choice is a complete, nonmutilating excision; chemotherapy may be given to patients who have microscopic or macroscopic residual disease, although the results are controversial; cytologic atypia and positive ALK status are more frequent in aggressive tumors, whereas metastatic tumors are negative for ALK; and HHV8 is not involved in the pathogenesis of IMT.

Management of the post chemotherapy subcentimeter residual mass: the case for observation

With the introduction of cisplatin-based chemotherapy, testis cancer has now become a highly curable disease. For patients presenting with good risk disease, the primary goal for physicians is to decrease the treatment-related morbidity without compromising cure. For low-volume ( 5 cm) stages II and III disease, initial treatment is typically systemic chemotherapy. Following the systemic chemotherapy, patients achieving a partial radiographic response (PR) generally undergo post chemotherapy (PC) surgery as 50–60% harbor either teratoma or active cancer. Thus, patients achieving a PR require dual therapy: chemotherapy plus surgery. The controversy arises as to the optimal treatment for patients achieving a complete radiographic response (CR) to systemic chemotherapy: observation or surgery. The argument for either approach relates to the interpretation of data on the ability of chemotherapy as monotherapy to cure patients with metastatic disease. As teratoma is chemorefractory, and residual microscopic teratoma may be present PC in complete responders, some institutions have adopted the policy for PC surgery in all patients including CRs. The rationale is twofold: (1) all patients with metastatic disease require dual therapy: chemotherapy to eradicate active germ cell tumor and surgery to eradicate microscopic teratoma as (2) unresected microscopic teratoma has an unpredictable biologic behavior and may ultimately have a deleterious eVect on outcome. Proponents of observation in those achieving a CR to chemotherapy argue that (1) PC microscopic teratoma may be by and large biologically benign, (2) the small relapse rates of those observed does not justify surgery in all patients achieving a CR and (3) patients that do relapse remain curable. This paper will address the incidence of microscopic teratoma in complete responders to chemotherapy, and attempt to deWne the biologic behavior of PC microscopic teratoma.

Renal cell carcinoma in the solitary kidney: report of six cases.

TWENTY-ONE cases of renal cell carcinoma in a solitary kidney have appeared in the literature. Six additional cases are reported. The chief interest of tomours lies in their unpredictable biological behaviour which impels the urologist to exert unorthodox methods of surgical attack.

Radical resection of a giant, invasive and symptomatic malignant Solitary Fibrous Tumour (SFT) of the pleura

Solitary Fibrous Tumours (SFTs) of the pleura are rare neoplasms, with unpredictable biological behaviour. Although usually benign, malignant SFTs are described, and they are often associated with large, necrotic and locally invasive tumours. Radical resection represents the treatment of choice in all cases; recurrences are uncommon, and redo-surgery should be considered. The case of a giant, invasive, radically resected malignant SFT, is described. The role of postoperative radiotherapy, to reduce the risk of recurrence, is also discussed.

Global gene expression profiling of oral cavity cancers suggests molecular heterogeneity within anatomic subsites

BackgroundOral squamous cell carcinoma (OSCC) is a frequent neoplasm, which is usually aggressive and has unpredictable biological behavior and unfavorable prognosis. The comprehension of the molecular basis of this variability should lead to the development of targeted therapies as well as to improvements in specificity and sensitivity of diagnosis.ResultsSamples of primary OSCCs and their corresponding surgical margins were obtained from male patients during surgery and their gene expression profiles were screened using whole-genome microarray technology. Hierarchical clustering and Principal Components Analysis were used for data visualization and One-way Analysis of Variance was used to identify differentially expressed genes. Samples clustered mostly according to disease subsite, suggesting molecular heterogeneity within tumor stages. In order to corroborate our results, two publicly available datasets of microarray experiments were assessed. We found significant molecular differences between OSCC anatomic subsites concerning groups of genes presently or potentially important for drug development, including mRNA processing, cytoskeleton organization and biogenesis, metabolic process, cell cycle and apoptosis.ConclusionOur results corroborate literature data on molecular heterogeneity of OSCCs. Differences between disease subsites and among samples belonging to the same TNM class highlight the importance of gene expression-based classification and challenge the development of targeted therapies.

Malignant proliferating trichilemmal tumor of the scalp: A case report

Malignant proliferating trichilemmal tumor is a rare skin tumor that affects mainly older women. It mimicks differential squamous cell carcinoma and its biological behavior is unpredictable. To report on a new case of malignant proliferating trichilemmal tumor of the scalp and to describe the clinical and histopathologic findings. A tumor measuring 2 cm was surgically excised with a 0.5 cm conservative margin of normal tissue Based on the histopathologic findings of tumor, this case was diagnosed as proliferating trichilemmal tumor of the scalp. Eleven months after tumor resection, the patient is free of disease. Malignant proliferating trichilemmal tumor is a rare malignant lesion with an unpredictable biological behavior. After wide excision, long term clinical follow up of the patient for early diagnosis of metastases is judicious.

Epithelioid hemangioendothelioma of the oral cavity

To investigate the clinicopathological characteristics and biologic behaviour of epithelioid hemangioendothelioma in the oral cavity. The clinical features and pathological findings of nine cases with intraoral epithelioid hemangioendothelioma were reviewed, including immunohistochemistry study. This series comprised seven males and two females aged 6-53 years (mean 28 years). The sites of the tumour included the tongue (n = 4), lip (n = 1), the gingiva and alveoli of the maxilla (n = 1), the gingiva and alveoli of the mandible (n = 1), buccal mucosa (n = 1), and the floor of the mouth (n = 1). A painless solitary mass was the most common presentation and was found in eight cases. On pathology, the tumour grew in short strands, cords or nests of polygonal to slightly spindled epithelioid cells in fibro-myxoid stroma, with formation of intracytoplasmic lumina. Tumour cells were immunoreactive to CD34, FVIIIRAg, and vimentin. Focal-positive cytokeration were observed in three cases. Immunoreactivity for S-100 protein, epithelial membrane antigen (EMA) and human herpesvirus (HHV)-8 was negative in all cases. Two cases recurred after surgical excision, but no patient developed local or distant metastasis. Wide local excision with long-term follow-up seems to be the treatment of choice for intraoral epithelioid hemangioendothelioma because of their unpredictable biological behaviour and recurrence potential.

High survivin expression is associated with favorable outcome in advanced primary oral squamous cell carcinoma after radiation therapy

Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive tumor phenotypes with unpredictable biological behavior. Recent studies suggested that high expression of the antiapoptotic protein survivin might be associated with adverse outcome in oral cancer patients. To investigate, whether increased copy numbers of the survivin-encoding gene BIRC5 results in elevated survivin levels and whether BIRC5 and survivin could serve as progression markers in the clinical course of OSCC, tumor tissue microarray analysis was performed applying fluorescence in situ hybridization and immunohistochemistry to 296 OSCC specimens. Gene copy number gain of BIRC5 was detected in 33.9% (150/227) of cases, which correlated significantly with high UICC stage and the presence of lymph node metastases (p = 0.003 and p = 0.001, respectively), but not with unfavorable patients' outcome (p > 0.05) in multivariate analysis. High survivin expression was found in 67.3% (169/251) of cases to predict increased 5- and 10-year overall survival of patients in a multivariate model including UICC stage and age as covariables (p = 0.035 and p = 0.026, respectively). Within a subgroup of patients, who received radiation therapy (n = 121), high survivin expression was found to be the only predictor of favorable 3-, 5- and 10-year overall survival in a multivariate cox regression analysis including UICC stage and age as covariables (p = 0.001, p = 0.004 and p = 0.006, respectively). In conclusion, high survivin expression might be useful to identify OSCC patients, who would benefit from radiotherapy.

Novel Diagnostic Scheme for Follicular Dendritic Cell Neoplasm: Clinicopathologic Analysis of 146 Cases.

Follicular dendritic cell neoplasm(FDCN), a rare tumor exhibiting a broad histopathological spectrum and unpredictable biologic behavior, has been classified into follicular dendritic cell tumor(FDCT) and follicular dendritic cell sarcoma(FDCS) regarded as borderline lesion and malignant tumor, respectively, by World Health Organization. But still no definite diagnostic criteria distinguishing FDCT from FDCS was established. Here in, as an approach to the differential diagnostic criteria, we performed clinicopathological analysis for 146 cases of FDCN, documented in English literature from January 1986 to May 2006. Through PubMED search with key words of FDC or dendritic cell tumor, we collected and reviewed 73 articles out of more than six thousands candidates, which contained 146 FDCNs with clinicopathological informations. We analyzed the carefully selected cases with parameters including age, gender, tumor location, tumor size, tumor margin, EBV association, mitosis, nuclear atypism, hemorrhage, necrosis and Castleman's disease association. Recurrence, metastasis and death of disease were referred as event. Kaplan-Meier model was used for overall event-free survival analysis and the log-rank test was used to assess statistical significance.Mitotic Index (MI, ≥ 5/10HPF vs <5/10HPF, P=0.0182) and tumor location (intraabdominal vs extraabdominal, P=0.007) showed significant association with event-free survival. But the other parameters have failed to achieve statistical significance as predictors of adverse events. For proposing diagnostic scheme, the risk groups were designated as follows: high risk group(n=7), MI ≥ 5/10HPF and intraabdominal; low risk group(n=26), MI <5/10HPF and extraabdominal; intermediate risk group(n=35), all others. These three risk groups had distinctly different median event-free survivals, 11 months, 24 months and 96 months for high, intermediate and low risk groups, respectively. And each group showed significantly different overall event-free survivals(P=0.0007). In conclusion, this novel diagnostic scheme might be a useful tool for predicting biologic behavior of FDCN.

Prognostic and Survival-Related Factors in Patients with Well-Differentiated Oligodendrogliomas

Oligodendrogliomas are brain tumors with unpredictable biological and clinical behavior. Prognostic factors related to survival are still controversial. The present study reviews 50 patients with well-differentiated (WHO grade II) oligodendrogliomas, located in the cerebral hemispheres and operated upon between 1980 and 1998. Prognostic factors studied include patient's age and sex, tumor location and extent, preoperative KPS, and extent of the surgical resection. The Ki-67 and the proliferative cell nuclear antigen (PCNA) levels were studied in all patients and some growth factors (GFs), including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and tenascine were examined in 20 patients. The long-term outcome and survival are not significantly correlated with the patient's age and sex, tumor location and extent, preoperative KPS and procedure for resection. Patients with lower Ki-67 and PCNA showed a significantly longer survival time (p < 0.001 and p < 0.019, respectively). Between 45 and 70 % of the tumors stained positive for one or more growth factors. Interestingly, cases with late recurrences (more than 4 years after surgery) and longer survival are significantly associated to negative GF expression or slight positivity, as compared with the variable and more often moderate immunoreactivity of cases with early anaplastic recurrences and shorter survival time. The presented data suggest that low proliferation indices and negative GF expression are associated with longer survival in well-differentiated oligodendrogliomas.

Clinicopathological Features of Solitary Fibrous Tumors of the Pleura: a Case Series and Literature Review

We assessed the clinicopathological features of solitary fibrous tumors of the pleura in a case series comprising 30 patients (20 women, 66.6%) with a mean age of 58.39 years. Forty-five percent of the cases were asymptomatic. In 70% of the cases the tumors arose in the visceral pleura. Twenty percent presented multiple tumors, a finding that was associated with intrapulmonary localization and malignant behavior (P<.0001) Histology revealed low cell density in 15% of the cases, moderate density in 50%, and high density in 35%; further findings showed atypia in 45% of the cases, necrosis in 25%, and hemorrhage in 15%. More than 4 mitoses per 10 high-power fields were noted in 30% of the cases. Immunohistochemistry results were positive for vimentin in all cases; cells were CD34+ in 85% of the cases, BCL2+ in 65%, and CD99+ in 40%. Findings for keratin and protein S100 were negative in all cases. Malignant biological behavior (local recurrence and metastasis) was observed in 4 cases, 2 of which were CD34-. Solitary fibrous tumors of the pleura are uncommon neoplasms with unpredictable biological behavior; follow-up should therefore be based on early detection of recurrence or metastasis.

Goblet cell carcinoid of the appendix

BackgroundGoblet cell carcinoid (GCC) of the appendix is a rare neoplasm that share histological features of both adenocarcinoma and carcinoid tumor. While its malignant potential remains unclear, GCC's are more aggressive than conventional carcinoid. The clinical presentations of this neoplasm are also varied. This review summarizes the published literature on GCC of the appendix. The focus is on its diagnosis, histopathological aspects, clinical manifestations, and management.MethodsPublished studies in the English language between 1966 to 2004 were identified through Medline keyword search utilizing terms "goblet cell carcinoid," "adenocarcinoid", "mucinous carcinoid" and "crypt cell carcinoma" of the appendix.ResultsBased on the review of 57 published papers encompassing nearly 600 diagnosed patients, the mean age of presentation for GCC of the appendix was 58.89 years with equal representation in both males and females. Accurate diagnosis of this neoplasm requires astute observations within an acutely inflamed appendix as this neoplasm has a prominent pattern of submucosal growth and usually lacks the formation of a well-defined tumor mass. The mesoappendix was involved in 21.64% followed by perineural involvement in 2.06%. The most common clinical presentations in order of frequency were acute appendicitis in 22.5%; asymptomatic in 5.4%; non-localized abdominal pain in 5.15% and an appendicular mass in 3.09%. The most common surgical treatment of choice was appendectomy with right hemicolectomy in 34.70% followed by simple appendectomy in 24.57%. Concomitant distant metastasis at diagnosis was present in 11.16% of patients with the ovaries being the most common site in 3.60% followed by disseminated abdominal carcinomatosis in 1.03%. Local lymph node involvement was seen in 8.76% of patients at the time of diagnosis. The reported 5-year survival ranges from 60 % to 84%. GCC's of the appendix remains a neoplasm of unpredictable biological behavior and thus warrants lifelong surveillance for recurrence of the disease upon diagnosis and successful surgical extirpation.ConclusionGCC of the appendix is a rare neoplasm. Due to its wide range of presentation, this tumor should be considered as a possible diagnosis in many varied situations leading to abdominal surgery. Histopathological features such as increased number of Paneth cells, increased amount of mucin secretion and presence of pancreatic polypeptide may predict a more aggressive behavior. The advocated plan of management recommended for patients with tumors that involve the adjacent caecum or with high-grade tumors with histological features such as an increased mitotic rate involve initial appendectomy with completion right hemicolectomy due to the high possibility of local recurrence with intraperitoneal seeding prior to lymph node involvement and a 20% risk of metastatic behavior. In female patients with GCC of the appendix regardless of age, bilateral salpingo-oophorectomy is advocated. In cases with obvious spread of the disease chemotherapy, mostly with 5-FU and leucovorin is advised. Cytoreductive surgery with adjuvant intraperitoneal chemotherapy can offer improved survival in cases with advanced peritoneal dissemination.

Allelic loss of tumor suppressor genes in ameloblastic tumors

Ameloblastoma is an odontogenic tumor with a variety of histologic appearances and an unpredictable biologic behavior. Little is known about allelic losses of tumor suppressor genes in ameloblastomas. This study surveyed DNA damage in ameloblastomas and correlated this with histologic sub-type and clinical outcome. There were 12 ameloblastomas (two peripheral, eight solid, and two unicystic) and three ameloblastic carcinoma studied for loss of heterozygosity of tumor suppressor genes on chromosomes 1p, 3p, 9p,10q, and 17p (L-myc, hOGG1, p16, pten, and p53). The frequency of allelic loss and the intratumoral heterogeneity were calculated. L-myc (71% frequency of allelic loss) and pten (62% frequency of allelic loss) had the most frequent allelic losses. Overall frequency of allelic loss and intratumoral heterogeneity were higher in mandibular and in unicystic tumors and lower in tumors that recurred/metastasized. The rate of allelic loss in the three carcinomas was similar to that seen in benign tumors. The frequency of allelic loss and intratumoral heterogeneity did not correlate with age, gender, histologic subtype, or prognosis. Since tumors that behaved aggressively did not harbor more allelic losses, it is likely that DNA damage in ameloblastomas and ameloblastic carcinomas is sporadic and cumulative. We conclude that other genetic or epigenetic mechanisms may be responsible for malignant behavior in ameloblastic carcinomas.

Sino-nasal haemangiopericytoma.

Hemangiopericytomas are very rare soft tissue tumors of vascular origin featurding pericyts distributed around vascular spaces. They have unpredictable biological behavior and a high local recurrence rate. Silver reticulin stain is essential for their histologic diagnosis. Approximately one third occur in the head and neck. Metastases occurs in nearly one half of all cases. They are relatively radioresistant despite their great vascular component. Wide local excision of the lesion, whenever feasible and lifelong follow-up should be the treatment of choice.