38 research outputs found
Polymorphous adenocarcinoma of the salivary glands: an overview of immunohistochemical features and insights on molecular pathology
Polymorphous adenocarcinoma (PAC),
represents a common minor salivary gland tumor (SGT)
characterized by local growth, low metastatic potential
and non-aggressive biologic behavior. Due to the clinical
aggressiveness noted in a subset of such tumors, the
former term polymorphous low-grade adenocarcinoma
(PLGA) was recently revised. PAC’s clinical features
and histological diversity result in clinical overlap of this
entity with several other SGTs including mainly adenoid
cystic carcinoma (AdCC). Differential diagnosis among
the entities is crucial, in terms of tumor management and
patients’ prognosis.
The aim of the present review is to summarize the
histological, cytological, immunohistochemical and
molecular features of PAC.
Histopathological examination is usually adequate
for PAC differential diagnosis from other SGTs, except
of AdCC. Several immunohistochemical markers
including c-Kit, S-100/ MG, Mcm-2 and Integrin β-1, -3,
-4, are reported to be useful diagnostic aids in borderline
cases. Limitations in sample numbers and study
methodology issues of the immunohistochemical PAC
studies complicate the identification and selection of
appropriate markers useful in the differential diagnosis.
Additionally, molecular analyses of PAC specimens
indicate that the PAC spectrum phenotypes result from
different genotypes (protein kinase D positive; PRKD(+)
and PRKD(-) tumors). PAC pathogenesis remains to be
determined in each particular genotype while the
convergence issue should be addressed in future studies
Clinical and Molecular Insights of Radiation-Induced Breast Sarcomas: Is There Hope on the Horizon for Effective Treatment of This Aggressive Disease?
Radiation-induced breast sarcomas (RIBS) are rare entities representing <1% of all primary breast malignancies, limiting most reports to small retrospective case series. They constitute a heterogeneous group of neoplasms, with high-grade angiosarcoma being the most common subtype. Other sarcoma histotypes, such as undifferentiated pleomorphic sarcoma and leiomyosarcoma, can also be identified. Radiation-induced breast angiosarcoma (RIBA) has an incidence of approximately 0.1% after breast-conserving therapy and arises mainly from the dermis of the irradiated breast. MYC gene amplification is highly indicative of secondary breast angiosarcomas. Their clinical presentation often mimics benign port-radiation lesions, leading to a delay in diagnosis and a lost window of opportunity for cure. Surgery with negative margins is the mainstay of treatment of localized RIBS. In the case of angiosarcoma, technical difficulties, including multifocality, infiltrative margins, and difficulty in assessing tumor margins, render surgical treatment quite challenging. A limited number of studies showed that adjuvant radiation therapy reduces local recurrences; therefore, it is proposed by many groups for large, high-grade tumors. Chemotherapy has been evaluated retrospectively in a small subset of patients, with some evidence supporting its use in angiosarcoma patients. Approximately half of patients with RIBA will show local recurrence. In the advanced setting, different therapeutic options are discussed in the review, including chemotherapy, antiangiogenic therapy, and immunotherapy, whereas the need for further research on molecular therapeutic targets is pointed out
Value of Combined Cytology and Molecular Information in the Diagnosis of Soft Tissue Tumors
The diagnosis of a soft tissue tumor (STT) is a complex process that
requires a multidisciplinary team consisting of a medical oncologist, a
radiologist, a pathologist, and a molecular biologist. The combination
of this information gives highly accurate results. Fine-needle
aspiration in this setting is one of the most performed techniques for
obtaining, in a noninvasive way, optimal material for morphological,
immunohistochemical, and molecular purposes. On the other hand, an
accurate tumor diagnosis is a dynamic process, as evidenced by the
constant modifications of international putative classifications, which
are more and more based on molecular aberrations (2013 World Health
Organization classification). In the future, STT classification will
certainly be a hybrid of morphology and molecular data and,
consequently, will be very useful for cytology. Cancer (Cancer
Cytopathol) 2015;123:141-151. (c) 2014 American Cancer Society.
Fine-needle aspiration in soft tissue tumors is one of the most
performed techniques for obtaining, in a noninvasive way, optimal
material for morphological, immunohistochemical, and molecular purposes
Evaluation of coxsackievirus and adenovirus receptor expression in human benign and malignant thyroid lesions
Coxsackievirus and adenovirus receptor (CAR) expression on tumor cells is associated with sensitivity to adenoviral infection, being considered as a surrogate marker for monitoring and/or predicting adenovirus-mediated gene therapy. The aim of this study was to evaluate the clinical significance of CAR expression in human benign and malignant thyroid lesions. CAR protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues from 107 patients with benign and malignant lesions and was statistically analyzed in relation to histopathologic type; tumor size; lymph node metastasis; capsular, lymphatic and vessel invasion; as well as follicular cells' proliferative capacity. CAR immunoreactivity was characterized as negative/weak in 53 (49.53%), moderate in 31 (28.97%) and strong in 23 (21.50%) of 107 thyroid cases. CAR immunoreactivity was significantly increased in malignant compared with that in benign thyroid lesions (p = 0.00002). Both malignant and benign thyroid lesions with enhanced follicular cells' proliferative capacity showed significantly increased CAR immunoreactivity (p = 0.00027). In malignant thyroid lesions, enhanced CAR immunoreactivity was significantly associated with larger tumor size (p = 0.0067). The current data revealed that CAR immunoreactivity could be considered of diagnostic utility in thyroid neoplasia. Further research effort is warranted to delineate whether CAR could be considered clinically important for both diagnosis and future (gene) therapeutic applications in thyroid neoplasia
Fine-needle aspiration in desmoplastic small round cell tumor: A report of 10 new tumors in 8 patients with clinicopathological and molecular correlations with review of the literature
BACKGROUND Desmoplastic small round cell tumor (DSRCT) is a rare round
cell sarcoma entity characterized by a specific t(11;22)(p13;q12)
translocation, usually intra-abdominal localization and an aggressive
clinical outcome. To date, only 35 DSRCT cases diagnosed by fine-needle
aspiration have been described. METHODS This study reports the
cytological diagnosis of DSRCT. Ten tumors from 8 patients were sampled
for diagnosis and analyzed to search the characteristic translocation
using fluorescence in situ hybridization or reverse transcription
polymerase chain reaction methods. RESULTS Smears were always
hypercellular and consisted of nonspecific round cell sarcoma. Nuclei
were polymorphic round, kidney-, or heart-shaped. Nuclear molding was
usually present. Paranuclear cytoplasmic densities were obvious and
noted in 7 cases. Cytonuclear atypia, mitotic figures, numerous crushed
nuclei, and apoptosis were frequently seen. Purple-stained stroma was
present in 8 cases (ranging from few connective tissue fragments to
large hyalinized deposits). Molecular studies based on cytological
aspirates were performed in 8 patients. The presence of the fusion gene
EWSR1-WT 1 transcript was identified in all, which confirmed the
diagnosis of DSRCT. CONCLUSIONS Smears showing poorly differentiated
round cells associated with cytoplasmic densities and connective stoma,
in a specific clinical context, young adult age, intra-abdominal
localization, suggestive immunocytochemical profile, and a unique
cytogenetic abnormality are highly specific and allow an accurate
diagnosis of DSRCT. Cancer (Cancer Cytopathol) 2014;122:386-393. (c)
2014 American Cancer Society
The Prognostic Values of PARP-1 Expression in Uveal Melanoma
Background: Uveal melanoma is the most common primary intraocular malignancy in adults. In advanced cases, the prognosis is very poor. Thus far, no effective methods of pharmacotherapy of this cancer have been found. The aim of the study was to evaluate the expression of PARP-1, the best-known member of the family of poly(ADP-ribose) polymerases, in uveal melanoma and its associations with clinicopathological parameters, overall survival, and disease-free survival. Methods: The study included 91 patients who underwent enucleation due to uveal melanoma. PARP-1 expression was assessed by immunohistochemistry. Results: High PARP-1 expression was associated with more frequent chromosome 3 loss, higher histopathological grade, bigger tumor size, and absence of intrascleral extension. High PARP-1 expression was associated with shorter overall survival time and disease-free survival time. Conclusions: The above findings indicate that high expression of PARP-1 can be considered as an unfavorable prognostic factor in uveal melanoma
The Prognostic Values of PARP-1 Expression in Uveal Melanoma
Background: Uveal melanoma is the most common primary intraocular malignancy in adults. In advanced cases, the prognosis is very poor. Thus far, no effective methods of pharmacotherapy of this cancer have been found. The aim of the study was to evaluate the expression of PARP-1, the best-known member of the family of poly(ADP-ribose) polymerases, in uveal melanoma and its associations with clinicopathological parameters, overall survival, and disease-free survival. Methods: The study included 91 patients who underwent enucleation due to uveal melanoma. PARP-1 expression was assessed by immunohistochemistry. Results: High PARP-1 expression was associated with more frequent chromosome 3 loss, higher histopathological grade, bigger tumor size, and absence of intrascleral extension. High PARP-1 expression was associated with shorter overall survival time and disease-free survival time. Conclusions: The above findings indicate that high expression of PARP-1 can be considered as an unfavorable prognostic factor in uveal melanoma