Acinic Carcinoma Research Articles

Adenoid cystic/basal cell carcinoma of the prostate:case report

Although most prostate carcinomas belong to the conventional acinar type, unusual variants have been reported. The adenoid cystic/basal cell carcinoma of the prostate is a rare tumor with distinctive histopathologic features. There are quite few publications in the literature concerning the diagnosis, treatment, and prognosis of this neoplasm. METHODS. A 71-year-old man had an increased PSA value (5.11 ng/dL); the prostatic biopsy examination was positive for adenoid cystic/basal cell carcinoma. For this reason we proceeded with radical prostatectomy. The histology examination showed an acinar conventional carcinoma and adenoid cystic/basal cell carcinoma. At eight months the patient did not show any recurrence. CONCLUSIONS. Various histologic and immunohistochemical features are helpful in recognizing the adenoid cystic/basal cell carcinoma of the prostate. Clinically, the only difference from a conventional adenocarcinoma is that the PSA value is usually normal or only slightly increased. This tumor has a biological potential that can result in metastases in some cases; the current treatment consists primarily in the surgical resection. A close, long-term follow-up is strongly recommended.

High-grade prostatic intraepithelial neoplasia, PIN-like carcinoma, ductal carcinoma, and intraductal carcinoma of the prostate

Many prostate lesions have ‘large gland’ morphology with gland size similar to or larger than benign glands, complex glandular architecture including papillary, cribriform, and solid, and significant cytological atypia in glandular epithelium with nucleomegaly, prominent nucleoli, or anisonucleosis. The most common and clinically important lesions with ‘large gland’ morphology include high-grade prostatic intraepithelial neoplasia (HGPIN), PIN-like carcinoma, ductal adenocarcinoma, and intraductal carcinoma. These lesions have diverse clinical significance and management implications. HGPIN refers to proliferation of glandular epithelium that displays severe cytological atypia within the confines of prostatic ducts and acini. A HGPIN diagnosis in biopsies connotes ~25% risk of detection of cancer in repeat biopsies. It has been accepted as the main precursor lesion to invasive carcinoma. PIN-like carcinoma is a variant of acinar carcinoma that is morphologically reminiscent of HGPIN and is composed of large cancer glands lined with pseudostratified epithelium. Its clinical outcome is similar to that of usual acinar carcinomas and is graded as Gleason score 3+3=6. Ductal adenocarcinoma comprises large glands lined with tall columnar and pseudostratified epithelium. It is more aggressive than acinar carcinomas and is associated with higher stage disease and greater risk of PSA recurrence and mortality. Intraductal carcinoma is an intraglandular/ductal neoplastic proliferation of glandular epithelial cells that results in marked expansion of glandular architecture and nuclear atypia that often exceeds that in invasive carcinomas. In majority of cases, it is thought to represent retrograde extension of invasive carcinoma into pre-existing ducts and acini. Rarely it may represent a peculiar form of carcinoma with predilection for intraductal location. It is considered an adverse pathological feature and is seen almost always in high-grade and volume carcinoma and harbingers worse clinical outcomes. This article reviews ‘new’ information on the clinical and pathological features of HGPIN, PIN-like carcinoma, ductal carcinoma, and intraductal carcinoma, and focuses morphological features that aid the differential diagnosis.

Sjögren syndrome hidden by previous parotidectomy and cervicofacial radiotherapy

Introduction: Sjögren’s syndrome (SS) is a chronic inflammatory auto-immune disease of the exocrine glands which incidence increases with age. Sex ratio is 9.9 female for 1 male. Observation: A 67-year-old female patient presented for xerostomia leading to major functional impairment. The medical history of the patient was pulmonary sarcoidosis, with join and adenoid involvement, considered as cured; left partial parotidectomy, with a diagnosis of acinous carcinoma, followed 7 years later by a total parotidectomy due to tumor recurrence, and followed by external radiotherapy (70 Gy). Arterial hypertension, hypothyroïditis and diabetes mellitus were also noticed. She reported xerostomia and xerophtalmia. Seric anti-SSA antibodies were positive and histologic findings were compatible with SS. Commentaries: Despite other co-morbidities, the diagnosis was hidden by previous parotidectomy and cervical radiotherapy. Thus, SS should not be underdiagnosed in patients with complex medical history.

Effects of a fixed herbal drug combination (Ze 185) to an experimental acute stress setting in healthy men – An explorative randomized placebo-controlled double blind study

ERG and PTEN have been suggested as potential prognostic markers in prostatic adenocarcinoma. We assessed the relationship between ERG and PTEN protein expression in cribriform architecture prostatic carcinomas and adjacent acinar non-cribriform carcinoma and determined the interobserver variability in assessment of these markers.A contemporary cohort of radical prostatectomy cases (n = 246) were reviewed and cribriform architecture carcinomas (intraductal carcinoma and cribriform Gleason 4 carcinomas) were identified and confirmed with triple cocktail immunostaining. ERG and PTEN protein expression were independently examined across all carcinoma components by two pathologists.57 cases were available for immunohistochemistry. ERG protein expression was concordant between the cribriform and non-cribriform acinar carcinomas in 56/57 cases. There was no interobserver discrepancy in ERG assessment. PTEN staining was concordant in 53/57 cases however 33 cases showed heterogeneous staining, most marked in the non-cribriform acinar component. The kappa value for interobserver assessment of PTEN scoring was 0.787 (moderate) with discrepant cases resolved by cooperative review.ERG protein expression shows almost complete concordance (98.2%) across cribriform and non-cribriform prostatic carcinomas. Assessment of this staining is straightforward and consistent between observers. PTEN protein expression is heterogeneous and results in only moderate interobserver agreement. Both staining heterogeneity and interpretation present challenges in analyzing PTEN protein expression.

Ductal variant of prostate adenocarcinoma harbor Xenotropic murine leukemia virus related virus (XMRV) infection: a novel finding in subtype of prostate cancer.

Xenotropic murine leukemia virus related virus (XMRV), is the first gammaretrovirus identified a decade ago, in human tissue bearing adenocarcinoma of prostate, followed by several researches documenting little or no prevalence of XMRV in prostate cancer samples. However, the status of XMRV within subtype of prostate adenocarcinoma has not been investigated yet. In this study, we investigated the relationship between XMRV and broad spectrum morphological entities of prostate adenocarcinoma, including acinar, ductal and other rare subtypes. The prevalence of XMRV DNA in different histological subtypes of prostate adenocarcinoma was examined after characterizing the tumors into groups, using formalin-fixed, paraffin-embedded tissue samples from newly diagnosed prostate adenocarcinomas and archival prostate cancer tissue from our XMRV case control analysis. Broad-spectrum XMRV DNA amplification was performed by end-point polymerase chain reaction, using commercially available primer set. The study included 100 patients with prostate cancer. XMRV DNA was detected in 4 of 8 (50%) ductal adenocarcinomas, exhibiting papillary and cribriform histological features. XMRV DNA was not detected in any other variant of adenocarcinoma including acinar (0/91) and mucinous carcinomas (0/1). Majority of XMRV positive cases were biologically aggressive and present cancer at an early age upon diagnosis. Ductal adenocarcinomas demonstrate a significant association of XMRV DNA while other histological variants of prostate adenocarcinoma seem unrelated to XMRV infection.

BRCA1/2 reversion mutations in prostate cancer identified from clinical tissue and liquid biopsy samples.

5024 Background: Prostate tumors with genomic alterations (GA) in BRCA1 or BRCA2 ( BRCA) may be sensitive to treatment with PARP inhibitors (PARPi). However, secondary reversion mutations (revGA) can arise that may restore BRCA function and underlie reduced sensitivity to PARPi or platinum (Pt)-based therapy. Comprehensive genomic profiling (CGP), using either tissue or liquid biopsies, can detect the variety of clinically relevant revGA that can arise. Methods: DNA extracted from FFPE tumor tissue or blood samples obtained during routine clinical care for 1911 patients with predominantly relapsed, refractory or metastatic prostate carcinoma was analyzed by hybrid-capture, next-generation sequencing for all classes of GA: base substitutions, indels, rearrangements, and copy number changes. RevGA were any GA that could restore the reading frame if in cis with a nonsense or frameshift (fs) GA. Results: 216/1911 (11.3% ± 1.4%) tumors had ≥1 deleterious BRCA GA. Of these, 7 samples harbored potential revGA in BRCA1 (1) or BRCA2 (6): prostate acinar adenocarcinoma (5), neuroendocrine carcinoma (1), or undifferentiated carcinoma (1). Of these, 2 samples were liquid biopsies (blood), 4 were FFPE tissue samples (liver), and 1 sample was a bone marrow core biopsy. All samples with revGA were metastases. Potential revGA were of 3 types: overlapping indel (4), compensatory fs (2), and missense (1). One case harbored 2 revGA, an overlapping indel and a compensatory fs. Alteration frequencies for TMPRSS2 (fusions), PTEN, and AR were similar with or without BRCA mutations; revGA-positive samples had a modest increase in PTEN alterations (42.9% vs 33.8%, NS). The frequency of CDK12 alterations was significantly reduced in BRCA-mutated tumors (0.9% vs 6.9%, p = 0.00002). Clinical histories for patients with reversion mutations will be presented. Conclusions: CGP of 1911 prostate carcinomas reveals ≥1 deleterious BRCA1/2 in 11.3% of samples. From these, a series of 7 cases, all metastases, with co-occurring potential revGA were identified. Although rare, revGA can be acquired during treatment and may underlie resistance to PARPi or Pt-based therapy. BRCA revGA can be detected from both tissue and liquid biopsies.

No Functional Role for microRNA-342 in a Mouse Model of Pancreatic Acinar Carcinoma.

The intronic microRNA (miR)-342 has been proposed as a potent tumor-suppressor gene. miR-342 is found to be downregulated or epigenetically silenced in multiple different tumor sites, and this loss of expression permits the upregulation of several key oncogenic pathways. In several different cell lines, lower miR-342 expression results in enhanced proliferation and metastasis potential, both in vitro and in xenogenic transplant conditions. Here, we sought to determine the function of miR-342 in an in vivo spontaneous cancer model, using the Ela1-TAg transgenic model of pancreatic acinar carcinoma. Through longitudinal magnetic resonance imaging monitoring of Ela1-TAg transgenic mice, either wild-type or knockout for miR-342, we found no role for miR-342 in the development, growth rate, or pathogenicity of pancreatic acinar carcinoma. These results indicate the importance of assessing miR function in the complex physiology of in vivo model systems and indicate that further functional testing of miR-342 is required before concluding it is a bona fide tumor-suppressor-miR.

MiR-29a-deficiency does not modify the course of murine pancreatic acinar carcinoma.

The development of cancers involves the complex dysregulation of multiple cellular processes. With key functions in simultaneous regulation of multiple pathways, microRNA (miR) are thought to have important roles in the oncogenic formation process. miR-29a is among the most abundantly expressed miR in the pancreas. Together with altered expression in pancreatic cancer cell lines and biopsies, and known oncogenic functions in leukemia, this expression data has identified miR-29a as a key candidate for miR involvement in pancreatic cancer biology. Here we used miR-29a-deficient mice and the TAg model of pancreatic acinar carcinoma to functionally test the role of miR-29a in vivo. We found no impact of miR-29a loss on the development or growth of pancreatic tumours, nor on the survival of tumour-bearing mice. These results suggest that, despite differential expression, miR-29a is oncogenically neutral in the pancreatic acinar carcinoma context. If these results are extended to other models of pancreatic cancer, they would reduce the attractiveness of miR-29a as a potential therapeutic target in pancreatic cancer.

No Effect of Dietary Aspartame or Stevia on Pancreatic Acinar Carcinoma Development, Growth, or Induced Mortality in a Murine Model.

Pancreatic cancer has an extremely poor prognosis, largely due to a poor record for early detection. Known risk factors for pancreatic cancer include obesity, diet, and diabetes, implicating glucose consumption and regulation as a key player. The role of artificial sweeteners may therefore be pertinent to disease kinetics. The oncogenic impact of artificial sweeteners is a highly controversial area. Aspartame, one of the most studied food additives, is widely recognized as being generally safe, although there are still specific areas where research is incomplete due to study limitations. Stevia, by contrast, has been the subject of relatively few studies, and the potential health benefits are based on extrapolation rather than direct testing. Here, we used longitudinal tracking of pancreatic acinar carcinoma development, growth, and lethality in a sensitized mouse model. Despite exposure to aspartame and stevia from the in utero stage onward, we found no disease modification activity, in either direction. These results contribute to the data on aspartame and stevia safety, while also reducing confidence in several of the purported health benefits.

Evaluation of ERG and PTEN protein expression in cribriform architecture prostate carcinomas

ERG and PTEN have been suggested as potential prognostic markers in prostatic adenocarcinoma. We assessed the relationship between ERG and PTEN protein expression in cribriform architecture prostatic carcinomas and adjacent acinar non-cribriform carcinoma and determined the interobserver variability in assessment of these markers.A contemporary cohort of radical prostatectomy cases (n=246) were reviewed and cribriform architecture carcinomas (intraductal carcinoma and cribriform Gleason 4 carcinomas) were identified and confirmed with triple cocktail immunostaining. ERG and PTEN protein expression were independently examined across all carcinoma components by two pathologists.57 cases were available for immunohistochemistry. ERG protein expression was concordant between the cribriform and non-cribriform acinar carcinomas in 56/57 cases. There was no interobserver discrepancy in ERG assessment. PTEN staining was concordant in 53/57 cases however 33 cases showed heterogeneous staining, most marked in the non-cribriform acinar component. The kappa value for interobserver assessment of PTEN scoring was 0.787 (moderate) with discrepant cases resolved by cooperative review.ERG protein expression shows almost complete concordance (98.2%) across cribriform and non-cribriform prostatic carcinomas. Assessment of this staining is straightforward and consistent between observers. PTEN protein expression is heterogeneous and results in only moderate interobserver agreement. Both staining heterogeneity and interpretation present challenges in analyzing PTEN protein expression.

A Rare Cause of Abdominal Pain to Consider: Solid Pseudopapillary Tumor of the Pancreas

Solid Pseudopapillary Neoplasm (SPN) of the pancreas also known as Frantz's tumor is an uncommon tumor that mainly occurs in women in their second to fourth decades of life. It accounts for less than 1% of pancreatic tumors and typically arises from the pancreatic tail. It is characterized by low potential for malignancy and a favorable prognosis after resection with 5 year survival rates approaching 85-95%. Diagnosis could be challenging as SPN tend to manifest with nonspecific abdominal symptoms, variable radiological features and inconsistent morphology. The cellular origin of SPN is unclear and might involve ductal, acinar, endocrine, or multipotent stem cells. Specific findings for cellular differentiation are indeterminate; hence accurate diagnosis depends on immunohistochemical staining. We report a rare case of a 27 year-old woman who presented with intermittent abdominal pain, nausea, vomiting and anorexia of 2 weeks duration. Her medical history was significant for recurrent abdominal wall abscesses after abdominoplasty a year ago. Physical examination revealed mild epigastric tenderness. Laboratory tests were unremarkable. Contrast computed tomography (CT) scan of abdomen showed a 2 x 2 cm indeterminate pancreatic tail lesion (Fig 1). An endoscopic ultrasound (EUS) disclosed a 2.1 x 1.8 cm hypoechoic mass in the tail of the pancreas (Fig 2). Trans-gastric fine needle aspiration was obtained to show clusters of uniform neoplastic cells with abundant cytoplasm and oval bean-shaped nuclei. Immunohistochemical stains were positive for CD10, CD56, Ck7, Cyclin D1 and cytoplasmic Beta Catenin but negative for chromogranin and E-Cadherin which was consistent with a pseudopapillary tumor (Fig 3). The patient underwent a robotic assisted en-bloc distal pancreatectomy and splenectomy. There were no intra-abdominal metastases. Despite the increasing number of SPN detected incidentally by imaging, this tumor remains infrequent and the presentation of individual cases can be unique. SPN is characterized by a specific immunohistological pattern, as demonstrated in our case, which makes it highly distinct from other pancreatic neoplasms particularly neuroendocrine tumors, acinar carcinomas and carcinoids. It is important to differentiate SPN from other pancreatic neoplasms because this neoplasm is amenable to cure after complete surgical resection even in cases with capsular invasion and distant metastases, unlike other malignant tumors of the pancreas.Figure 1Figure 2Figure 3

Acinar neoplasms of the pancreas-A summary of 25 years of research.

Our understanding about the family of acinar neoplasms of the pancreas has grown substantially over the past 25 years. The prototype is acinar cell carcinoma, an uncommon variant of pancreatic carcinoma that demonstrates production of pancreatic exocrine enzymes, verifiable using immunohistochemistry, and exhibits characteristic histologic features. Related neoplasms include mixed acinar carcinomas such as mixed acinar neuroendocrine carcinoma and mixed acinar ductal carcinoma. In the pediatric age group, pancreatoblastoma is also closely related. Cystic and extrapancreatic forms have been described. These neoplasms share molecular alterations that are distinct from the more common ductal and neuroendocrine neoplasms of the pancreas. Although there is a broad range of genetic findings, a number of potential therapeutic targets have emerged. This review explores the clinical and pathologic features of pancreatic acinar neoplasms along with their more common molecular phenotypes. The differential diagnosis with other pancreatic neoplasms is explored as well.

Pancreatic panniculitis as a paraneoplastic phenomenon of a pancreatic acinar cell carcinoma

We present the case of a 59-year-old patient admitted with extreme painful erythematous subcutaneous nodules of the lower extremities in association with arthritis and peripheral eosinophilia. Upon skin biopsy, the diagnosis of pancreatic panniculitis was made. On further investigation, an underlying acinar cell type pancreas carcinoma was revealed. This clinical case does illustrate how a seemingly innocuous skin condition may herald an underlying malignant disease. The presence of pancreatic panniculitis should trigger clinicians to undertake further thorough diagnostic investigation of the pancreas.

A randomized, multicenter, double-blind, placebo-controlled study of the Bruton tyrosine kinase inhibitor, ibrutinib, versus placebo in combination with nab-paclitaxel and gemcitabine in the first-line treatment of patients with metastatic pancreatic adenocarcinoma (RESOLVE).

TPS483 Background: Advanced pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and short survival. Nab-paclitaxel/gemcitabine (Nab-P/GCB) is a preferred regimen for front-line treatment. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (ibr) shows antitumor activity in preclinical PDAC models, in part, due to modulation of the tumor microenvironment. Ibr treatment inhibits mast-cell degranulation and decreases tumor-associated inflammation and desmoplasia with simultaneous enhanced presence and activity of cytotoxic T cells in tumors (Affara et al, Cancer Cell, 2014; Masso-Valles et al, Cancer Res, 2015). This randomized trial will evaluate the efficacy of ibr in combination with Nab-P/GCB. Methods: The randomized, multicenter, double-blind RESOLVE trial (NCT02436668; PCYC-1137-CA) will compare ibr vs. placebo in combination with Nab-P/GCB in approximately 320 patients with untreated metastatic PDAC. Key eligibility criteria include histologically confirmed metastatic PDAC; stage IV diagnosis within 6 weeks of randomization; adequate hematologic, hepatic, and renal function; and Karnofsky performance score ≥ 70. Key exclusion criteria include prior therapies (chemotherapy for primary PDAC, BTK inhibitor, or radiotherapy), neuroendocrine or acinar pancreatic carcinoma, known brain or leptomeningeal disease, and history of stroke or intracranial hemorrhage < 6 months prior to enrollment. Patients will be randomized to oral ibr (560 mg) or matched placebo given daily in combination with Nab-P (125 mg/m2) and GCB (1,000 mg/m2) on days 1, 8, and 15 of a 28-day cycle until disease progression or treatment is no longer tolerated. A safety run-in phase will evaluate the ibr combination prior to the randomization portion of the study. The primary endpoint is progression-free survival; secondary endpoints include overall survival and safety. Enrollment in the trial has been initiated. Clinical trial information: NCT02436668.

Abstract 1475: Therapeutic responses in a novel patient-derived xenograft mouse model for rare acinar cell pancreatic carcinoma

Abstract Acinar cell carcinoma of the pancreas (ACC) is an uncommon malignancy, accounting for less than 1% of all pancreatic neoplasms. Because of its rarity, only a few retrospective studies are available to help guide management. We previously reported the case of a patient with metastatic ACC who achieved prolonged survival with doxorubicin as a result of personalized treatment designed in part on the basis of molecular and in-vitro data collected on analysis of the tumor and primary cells in culture developed from the liver metastasis. We now report the characterization of a patient derived xenograft (PDX) mouse model originating from this patient's ACC liver metastasis tissue. Antitumor activity of multiple drugs (5-FU, irinotecan, oxaliplatin, gemcitabine, bevacizumab, erlotinib, doxorubicin and imatinib) used as single agent therapy is demonstrated. Of the targeted and cytotoxic therapies used, oxaliplatin produced a dramatic and prolonged response to therapy even after withdrawal of treatment. Bevacizumab produced a significant response, as well. Serum lipase and tissue amylase levels correlated with the antitumor response to therapy. Thus, we have developed and characterized an ACC PDX model that may be used in drug discovery for the treatment of this rare cancer for which no standard of care exists. Note: This abstract was not presented at the meeting. Citation Format: Laura A. Marlow, Adam C. Mathias, Louis K. Dawson, William F. Durham, Kenneth A. Meshaw, Robert J. Mullin, Aidan J. Synnott, Ricardo Paz-Fumagalli, Murli Krishna, Daniel Von Hoff, Daniel L. Small, Gerardo Colon-Otero, John A. Copland. Therapeutic responses in a novel patient-derived xenograft mouse model for rare acinar cell pancreatic carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1475. doi:10.1158/1538-7445.AM2015-1475

PTEN loss and ERG protein expression are infrequent in prostatic ductal adenocarcinomas and concurrent acinar carcinomas.

Prostatic ductal adenocarcinoma is an unusual and aggressive morphologic subtype of prostate cancer. PTEN gene deletion and ERG gene rearrangement are among the most common genomic changes in acinar prostate cancers. Though ductal adenocarcinoma most commonly occurs with synchronous usual-type acinar adenocarcinoma, little is known about the molecular phenotype of these mixed tumors. We used genetically validated immunohistochemistry (IHC) assays to assess PTEN and ERG status in a group of 37 surgically treated ductal adenocarcinomas and 18 synchronous acinar adenocarcinomas where we have previously reported ERG gene rearrangement status by fluorescence in situ hybridization (FISH). A group of 34 stage and grade-matched pure acinar adenocarcinoma cases was studied as a control. ERG IHC was highly concordant with ERG FISH results, with 100% (36/36) concordance among ductal adenocarcinomas and 91% (31/34) concordance among 34 pure acinar carcinomas. Similar to previous FISH results, ERG expression by IHC was significantly less common among ductal adenocarcinomas (11% or 4/37) and their synchronous acinar tumors (6% or 1/18) compared to matched pure acinar adenocarcinoma cases (50% or 17/34; P = 0.0005 and 0.002, respectively). PTEN loss by IHC was also less common among ductal adenocarcinomas (18% or 6/34) and their synchronous acinar tumors (22% or 4/18) compared to matched pure acinar carcinomas (50% or 17/34; P = 0.01 and 0.08, respectively). As expected, PTEN loss was enriched among ERG positive compared to ERG-negative tumors in the pure acinar tumor control group (2.5-fold enrichment; P = 0.04) however this was not observed among the ductal adenocarcinomas (1.5 fold enrichment; P = NS). Of ductal adenocarcinomas with an evaluable synchronous acinar component, ERG status was concordant in 94% (17/18) and PTEN status was concordant in 94% (16/17). Based on PTEN and ERG, ductal adenocarcinomas and their concurrent acinar carcinomas may be clonally related in some cases and show important molecular differences from pure acinar carcinoma.

Pseudohyperplastic prostate carcinoma: histologic patterns and differential diagnosis.

The similarity between some carcinomas and many benign glandular proliferations has been mentioned in the literature for decades. The description of the main histologic features of pseudohyperplastic carcinoma has been very useful in avoiding errors of interpretation, particularly false-negative results. In recent years, we have found some histologic variants of this neoplasm that have not been mentioned previously. In order to classify the different histologic growth patterns and comment on their differential diagnosis, we reviewed the architectural and cytologic features of 34 cases of pseudohyperplastic adenocarcinoma in 2 radical prostatectomies, 4 transurethral resections, and 28 needle biopsies. Growth patterns most commonly observed included nodular, complex, and mixed (nodular and complex) patterns. Other less frequent histologic varieties included adenosis-like pattern, prostatic intraepithelial neoplasia-like pattern, pseudohyperplastic adenocarcinoma with xanthomatous features, and limited pseudohyperplastic adenocarcinoma. Frequent changes in neoplastic glands included papillary infoldings, large/cystic glands, and branching. Criteria associated with malignancy include nuclear enlargement (92%), apparent nucleoli (85%), pink amorphous secretions (78%), and transition to small acinar carcinoma (70%). However, in some biopsies, nuclear atypia was little apparent. Fifteen of the 34 cases were misdiagnosed as benign and 5 as other malignant neoplasms, and included the following diagnoses: hyperplastic nodules (11), prostatic adenosis (2), diffuse adenosis of the peripheral zone (1), benign cystic glands (1), and less frequently other malignant tumors including xanthomatous carcinoma (2), low-grade prostatic adenocarcinoma (2), and atrophic carcinoma (1). It is important to recognize the different growth patterns of this neoplasm in order to avoid an underdiagnosis of malignancy.

Neurogenin 3–Directed Cre Deletion of Tsc1 Gene Causes Pancreatic Acinar Carcinoma

The role of tuberous sclerosis complex (TSC) in the pathogenesis of pancreatic cancers remains largely unknown. The present study shows that neurogenin 3 directed Cre deletion of Tsc1 gene induces the development of pancreatic acinar carcinoma. By cross-breeding the Neurog3-cre mice with Tsc1loxp/loxp mice, we generated the Neurog3-Tsc1−/− transgenic mice in which Tsc1 gene is deleted and mTOR signaling activated in the pancreatic progenitor cells. All Neurog3-Tsc1−/− mice developed notable adenocarcinoma-like lesions in pancreas starting from the age of 100days old. The tumor lesions are composed of cells with morphological and molecular resemblance to acinar cells. Metastasis of neoplasm to liver and lung was detected in 5% of animals. Inhibition of mTOR signaling by rapamycin significantly attenuated the growth of the neoplasm. Relapse of the neoplasm occurred within 14days upon cessation of rapamycin treatment. Our studies indicate that activation of mTOR signaling in the pancreatic progenitor cells may trigger the development of acinar carcinoma. Thus, mTOR may serve as a potential target for treatment of pancreatic acinar carcinoma.

Rb Loss Is Characteristic of Prostatic Small Cell Neuroendocrine Carcinoma

Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide the diagnosis and therapy of this aggressive tumor. We examined the status of RB1, TP53, and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy-number alteration analysis, and sequencing of formalin-fixed paraffin-embedded specimens. We found retinoblastoma (Rb) protein loss in 90% of small cell carcinoma cases (26 of 29) with RB1 allelic loss in 85% of cases (11 of 13). Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3 of 7) showed Rb protein loss. In contrast, only 7% of primary high-grade acinar carcinomas (10 of 150), 11% of primary acinar carcinomas with neuroendocrine differentiation (4 of 35), and 15% of metastatic castrate-resistant acinar carcinomas (2 of 13) showed Rb protein loss. Loss of PTEN protein was seen in 63% of small cell carcinomas (17 of 27), with 38% (5 of 13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% of small cell carcinomas (14 of 25), with 60% of cases (6 of 10) showing TP53 mutation. Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by a validated IHC assay. As Rb protein loss rarely occurs in high-grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target.

Tumeurs malignes de la parotide : épidémiologie au Togo

We had for aim to determine the epidemiological profile of malignant parotid tumors in sub-Saharan country: Togo. We retrospectively studied the files of patients seen and treated for malignant parotid tumors, from January 1989 to December 31, 2008, at the Tokoin teaching hospital. Patients treated for another malignant tumor at the same time were excluded from the study. Ninety-six patients were included. Thirty-one tumors (32.29%) were malignant, in 18male and 13female patients with a sex ratio of 1.38. The average age was 39years (range 24-70years of age). Two patients could not undergo surgery. Histologically, there were 10cases of squamous cell carcinoma (32.26%), 6cases of adenoid cystic carcinoma (19.4%), 6cases of adenocarcinoma (19.4%), 4cases of carcinoma in pleomorphic adenoma (12.90%), 3cases of mucoepidermoid carcinoma (9.7%), 1case of acinar carcinoma (3.2%), and 1case of cystadenocarcinoma (3.2%). Squamous cell carcinoma was the most frequent histological type observed in Togo, contrary to literature data for which mucoepidermoid carcinoma is the most frequent malignant parotid tumor.