Nonsquamous Lesions of the Vulvar Skin and Subcutaneous Tissue: A Review (Part 2).

OBJECTIVE: The aim of this second article was to complete part 1 review of nonsquamous lesions of the vulvar skin and subcutaneous tissue (Journal of Lower Genital Tract Disease, 2021), clinically and pathologically, based on the fifth edition of the World Health Organization tumor classification. MATERIALS AND METHODS: A database search of PubMed and Google Scholar was performed between 1970 and 2021, using the search terms "vulva," "lower genital tract," and "non-squamous lesions." The search was limited to "human gynecological pathology." Full article texts were reviewed, and reference lists were screened for additional articles. We excluded abstracts and articles written in the non-English language. RESULTS: An initial list of 400 articles was identified. Thirty-seven articles discussed clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue. CONCLUSIONS: Clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue as categorized by the updated World Health Organization classification are presented.

Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis.

Macroautophagy (autophagy hereafter) degrades and recycles proteins and organelles to support metabolism and survival in starvation. Oncogenic Ras up-regulates autophagy, and Ras-transformed cell lines require autophagy for mitochondrial function, stress survival, and engrafted tumor growth. Here, the essential autophagy gene autophagy-related-7 (atg7) was deleted concurrently with K-ras(G12D) activation in mouse models for non-small-cell lung cancer (NSCLC). atg7-deficient tumors accumulated dysfunctional mitochondria and prematurely induced p53 and proliferative arrest, which reduced tumor burden that was partly relieved by p53 deletion. atg7 loss altered tumor fate from adenomas and carcinomas to oncocytomas-rare, predominantly benign tumors characterized by the accumulation of defective mitochondria. Surprisingly, lipid accumulation occurred in atg7-deficient tumors only when p53 was deleted. atg7- and p53-deficient tumor-derived cell lines (TDCLs) had compromised starvation survival and formed lipidic cysts instead of tumors, suggesting defective utilization of lipid stores. atg7 deficiency reduced fatty acid oxidation (FAO) and increased sensitivity to FAO inhibition, indicating that with p53 loss, Ras-driven tumors require autophagy for mitochondrial function and lipid catabolism. Thus, autophagy is required for carcinoma fate, and autophagy defects may be a molecular basis for the occurrence of oncocytomas. Moreover, cancers require autophagy for distinct roles in metabolism that are oncogene- and tumor suppressor gene-specific.

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.

BACKGROUND: Adjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC. METHODS: We did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805. FINDINGS: Between June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment. INTERPRETATION: Addition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC. FUNDING: National Cancer Institute of the National Institutes of Health.

Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial.

BACKGROUND: Erlotinib is approved for the treatment of all patients with advanced non-small-cell lung cancer (NSCLC), but is most active in the treatment of EGFR mutant NSCLC. Cabozantinib, a small molecule tyrosine kinase inhibitor, targets MET, VEGFR, RET, ROS1, and AXL, which are implicated in lung cancer tumorigenesis. We compared the efficacy of cabozantinib alone or in combination with erlotinib versus erlotinib alone in patients with EGFR wild-type NSCLC. METHODS: This three group, randomised, controlled, open-label, multicentre, phase 2 trial was done in 37 academic and community oncology practices in the USA. Patients were eligible if they had received one or two previous treatments for advanced non-squamous, EGFR wild-type, NSCLC. Patients were stratified by performance status and line of therapy, and randomly assigned using permuted blocks within strata to receive open-label oral daily dosing of erlotinib (150 mg), cabozantinib (60 mg), or erlotinib (150 mg) and cabozantinib (40 mg). Imaging was done every 8 weeks. At the time of radiographic progression, there was optional crossover for patients in either single-drug group to receive combination treatment. The primary endpoint was to compare progression-free survival in patients given erlotinib alone versus cabozantinib alone, and in patients given erlotinib alone versus the combination of erlotinib plus cabozantinib. We assessed the primary endpoint in the per-protocol population, which was defined as all patients who were eligible, randomly assigned, and received at least one dose of treatment. The safety analysis population included all patients who received study treatment irrespective of eligibility. This trial is registered with ClinicalTrials.gov, number NCT01708954. FINDINGS: Between Feb 7, 2013, and July 1, 2014, we enrolled and randomly assigned 42 patients to erlotinib treatment, 40 patients to cabozantinib treatment, and 43 patients to erlotinib plus cabozantinib treatment, of whom 111 (89%) in total were included in the primary analysis (erlotinib [n=38], cabozantinib [n=38], erlotinib plus cabozantinib [n=35]). Compared with erlotinib alone (median 1·8 months [95% CI 1·7-2·2]), progression-free survival was significantly improved in the cabozantinib group (4·3 months [3·6-7·4]; hazard ratio [HR] 0·39, 80% CI 0·27-0·55; one-sided p=0·0003) and in the erlotinib plus cabozantinib group (4·7 months [2·4-7·4]; HR 0·37, 0·25-0·53; one-sided p=0·0003). Among participants included in the safety analysis of the erlotinib (n=40), cabozantinib (n=40), and erlotinib plus cabozantinib (n=39) groups, the most common grade 3 or 4 adverse events were diarrhoea (three [8%] cases in the erlotinib group vs three [8%] in the cabozantinib group vs 11 [28%] in the erlotinib plus cabozantinib group), hypertension (none vs ten [25%] vs one [3%]), fatigue (five [13%] vs six [15%] vs six [15%]), oral mucositis (none vs four [10%] vs one [3%]), and thromboembolic event (none vs three [8%] vs two [5%]). One death due to respiratory failure occurred in the cabozantinib group, deemed possibly related to either drug, and one death due to pneumonitis occurred in the erlotinib plus cabozantinib group, deemed related to either drug or the combination. INTERPRETATION: Despite its small sample size, this trial showed that, in patients with EGFR wild-type NSCLC, cabozantinib alone or combined with erlotinib has clinically meaningful, superior efficacy to that of erlotinib alone, with additional toxicity that was generally manageable. Cabozantinib-based regimens are promising for further investigation in this patient population. FUNDING: ECOG-ACRIN Cancer Research Group, National Cancer Institute of the National Institutes of Health.

Pseudoangiomatous stromal hyperplasia of the vulva presenting as a polypoid vulvar lesion: a lesion associated with anogenital mammary-like tissue-report of a case and review of the literature.

OBJECTIVE: The study aimed to report the case of a patient with a polypoid vulvar lesion clinically thought to be an aggressive angiomyxoma. MATERIALS AND METHODS: On examination, a 4.0 × 2.0 × 1.5-cm polypoid lesion was seen on the right labium majus. RESULTS: Histopathological findings of the excised mass were consistent with pseudoangiomatous stromal hyperplasia of the vulva CONCLUSIONS: Pseudoangiomatous stromal hyperplasia is a lesion of breast tissue but can occur in anogenital mammary-like glands. It must be distinguished from low-grade angiosarcoma.

Metastatic Pleomorphic Lobular Carcinoma of the Breast to the Hypothalamus Presenting as a Primary Pituitary Lesion Presenting 17 Years Later-Report of a Case and Review of the Literature.

Carcinomas metastatic to the brain are common, however, metastatic disease to the hypothalamic- pituitary region is uncommon and account for less than 3.6% of all resected malignant pituitary tumors. Most metastatic disease in that region derives from a lung or breast primary, with both ductal and lobular carcinoma reported. We report what we believe is the first case of pleomorphic lobular carcinoma metastatic to the hypothalamus. This case is also reaffirms that late metastasis from breast cancer should be considered in the differential diagnosis. It is important for the clinician to consider the clinical history of breast cancer, even when remote, in the differential diagnosis.

Low tidal volume and high positive end-expiratory pressure mechanical ventilation results in increased inflammation and ventilator-associated lung injury in normal lungs.

BACKGROUND: Protective mechanical ventilation with low tidal volume (Vt) and low plateau pressure reduces mortality and decreases the length of mechanical ventilation in patients with acute respiratory distress syndrome. Mechanical ventilation that will protect normal lungs during major surgical procedures of long duration may improve postoperative outcomes. We performed an animal study comparing 3 ventilation strategies used in the operating room in normal lungs. We compared the effects on pulmonary mechanics, inflammatory mediators, and lung tissue injury. METHODS: Female pigs were randomized into 3 groups. Group H-Vt/3 (n = 6) was ventilated with a Vt of 15 mL/kg predicted body weight (PBW)/positive end-expiratory pressure (PEEP) of 3 cm H(2)O, group L-Vt/3 (n = 6) with a Vt of 6 mL/kg PBW/PEEP of 3 cm H(2)O, and group L-Vt/10 (n = 6) with a Vt of 6 mL/kg PBW/PEEP of 10 cm H(2)O, for 8 hours. Hemodynamics, airway mechanics, arterial blood gases, and inflammatory markers were monitored. Bronchoalveolar lavage (BAL) was analyzed for inflammatory markers and protein concentration. The right lower lobe was assayed for mRNA of specific cytokines. The right lower lobe and right upper lobe were evaluated histologically. RESULTS: In contrast to groups H-Vt/3 and L-Vt/3, group L-Vt/10 exhibited a 6-fold increase in inflammatory mediators in BAL (P < 0.001). Cytokines in BAL were similar in groups H-Vt/3 and L-Vt/3. Group H-Vt/3 had a significantly lower lung injury score than groups L-Vt/3 and L-Vt/10. CONCLUSION: Comparing intraoperative strategies, ventilation with high PEEP resulted in increased production of inflammatory markers. Low PEEP resulted in lower levels of inflammatory markers. High Vt/low PEEP resulted in less histologic lung injury.

Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico.

Targeted therapy has changed the paradigm of advanced NSCLC management by improving the survival rate of patients carrying actionable gene alterations using specific inhibitors. The epidemiologic features of these alterations vary among races. Understanding the racial differences benefits drug development, clinical trial design, and health resource allocation. Compared to Caucasian and Asian populations, current knowledge on Hispanic patients is less and no data of Hispanic patients from Puerto Rico have been reported. We retrieved and analyzed the demographic, clinical, and molecular data of Hispanic NSCLC patients from Puerto Rico with molecular tests performed in the Genoptix Medical Laboratory in Carlsbad, CA, USA between 2011 and 2018. The majority of the NSCLC patients in our study had either adenocarcinoma (75.4%) or squamous cell carcinoma (15.1%). The incidence of EGFR mutations was 24%. They were more common in female and younger patients (<60 years). The deletion of Exon 19 and Exon 21 L858R comprised 55.1% and 31.0% of all EGFR mutations, respectively. The frequency of the T790M mutation was lower compared to that of Hispanic patients reported in the literature (0.5% vs. 2.1%). In addition, 18.7% of the patients were positive for KRAS mutations, which was at the high end of that reported in Hispanic patients. Other driver gene alterations, ALK, MET, RET, ROS1, KRAS, ERBB2, etc., demonstrated similar incidences, as well as gender and age distributions to those previously reported. The KRAS/TP53 and KRAS/STK11 co-mutations were of very low frequencies (3.6%), which could potentially affect the responsiveness to PD1/PD-L1 immunotherapy. Our study demonstrated that the prevalence of NSCLC gene alterations in Hispanic patients from Puerto Rico was comparable to the reported average prevalence in Latin American countries, supporting the intermediate NSCLC gene alteration rate of Hispanic patients between Asian and Caucasian patients. Novel information of the frequencies of KRAS mutation subtypes, driver gene alterations in ROS1, BRAF, and ERBB2, and passenger gene alterations including a rare case with the FGFR2-TACC2 translocation in Hispanic NSCLC patients from Puerto Rico were also described.

Phase I neoadjuvant study of intravesical recombinant fowlpox-GM-CSF (rF-GM-CSF) or fowlpox-TRICOM (rF-TRICOM) in patients with bladder carcinoma.

Intravesical BCG is a highly effective treatment for high-grade nonmuscle invasive bladder cancer and carcinoma in situ (CIS); however, for patients who are either resistant or become unresponsive to BCG therapy there is a need for alternative treatment approaches. This study examined the safety and feasibility of intravesically administered recombinant fowlpox virus encoding GM-CSF (Arm A) or TRICOM (Arm B); and the local and systemic immunologic responses generated to the vector(s). Twenty bladder cancer patients scheduled for cystectomy as their standard of care received preoperatively four weekly doses of intravesical recombinant fowlpox. Treatment was well tolerated, however, three patients experienced transient elevations of liver transaminases, with one rising to the level of a DLT. Cystectomy derived tumor and normal bladder mucosa demonstrated mRNA for the virally encoded LacZ gene supporting effective infection/transfection. Detected serum antibody to the LacZ encoding ß-galactosidase indicated successful expression of vector-encoding gene products and the ability to immunize via the bladder site. H&E and IHC using a panel of immune cell specific antigens demonstrated immune cell infiltration of the bladder wall. These findings demonstrate good safety profile, successful infection/transfection, ability to generate systemic immune response, and local recruitment of immune cell populations with intravesical administration of fowlpox-based constructs encoding for GM-CSF(rF-GM-CSF) or TRICOM (rF-TRICOM), and support further evaluation of this treatment modality for bladder cancer.

An immunohistochemical method for identifying fibroblasts in formalin-fixed, paraffin-embedded tissue.

Fibroblasts are critical for tissue homeostasis, and their inappropriate proliferation and activation can result in common and debilitating conditions including fibrosis and cancer. We currently have a poor understanding of the mechanisms that control the growth and activation of fibroblasts in vivo, in part because of a lack of suitable fibroblast markers. We have taken advantage of an antibody previously shown to stain stromal cells in frozen tissues (TE-7) and identified conditions in which it can be used to stain fibroblasts and myofibroblasts in the paraffin-embedded tissue samples routinely collected for pathological analysis. We show that this antibody recognizes growing and quiescent fibroblasts and myofibroblasts by immunohistochemistry, immunofluorescence, and ELISA assays. We also present its staining patterns in normal tissue samples and in breast tumors.

Preoperative fine needle aspiration cytology diagnosis of microcystic adenoma of the pancreas: fact or fiction? A report of 2 cases.

BACKGROUND: Microcystic adenoma is an uncommon benign neoplasm involving the pancreas that usually affects older populations. These neoplasms often enlarge to significant sizes, causing symptoms of obstruction and discomfort. CASES: We report 2 cases of microcystic adenoma of the pancreas in which an accurate diagnosis could not be rendered on cytology material alone. Bench fine needle aspiration (FNA) biopsy performed on the resection specimen in one of the cases had a higher cellular yield because a different technique was used to prepare the slide. CONCLUSION: A preoperative diagnosis can be helpful in guiding the care of the patient, thereby increasing the importance of a diagnosis to distinguish between a benign vs. malignant process. These case reports demonstrate the difficulty of obtaining diagnostic cells in microcystic adenoma, highlight the use of FNA to increase cellular yield and emphasize the importance of correlating radiologic findings with aspiration of abundant watery fluid from cystic pancreatic masses to make a definitive diagnosis.

Cellular angiofibroma is genetically similar to spindle cell lipoma: a case report.

Cellular angiofibroma is a benign mesenchymal neoplasm of female and male genital tract composed of prominent vasculature and stromal spindle cells, often with admixture of adipose tissue. The tumor has histomorphologic similarities to angiomyofibroblastoma and spindle cell lipoma. Herein we describe a tumor arising in the perineal region of a 60-year-old man with morphological and immunohistochemical features of cellular angiofibroma and showing cytogenetic characteristics similar to spindle cell lipoma. To our knowledge, this is the first report of cytogenetic changes in cellular angiofibroma. The genetic overlap of these entities supports their origin from the same mesenchymal stem cell.

Gene Methylation Biomarkers in Sputum and Plasma as Predictors for Lung Cancer Recurrence.

Detection of methylated genes in exfoliated cells from the lungs of smokers provides an assessment of the extent of field cancerization, is a validated biomarker for predicting lung cancer, and provides some discrimination when interrogated in blood. The potential utility of this 8-gene methylation panel for predicting tumor recurrence has not been assessed. The Eastern Cooperative Oncology Group initiated a prevention trial (ECOG-ACRIN5597) that enrolled resected stage I non-small cell lung cancer patients who were randomized 2:1 to receive selenized yeast versus placebo for 4 years. We conducted a correlative biomarker study to assess prevalence for methylation of the 8-gene panel in longitudinally collected sputum and blood after tumor resection to determine whether selenium alters their methylation profile and whether this panel predicts local and/or distant recurrence. Patients (N = 1,561) were enrolled into the prevention trial; 565 participated in the biomarker study with 122 recurrences among that group. Assessing the association between recurrence and risk of gene methylation longitudinally for up to 48 months showed a 1.4-fold increase in OR for methylation in sputum in the placebo group independent of location (local or distant). Kaplan-Meier curves evaluating the association between number of methylated genes and time to recurrence showed no increased risk in sputum, while a significant HR of 1.5 was seen in plasma. Methylation detection in sputum and blood is associated with risk for recurrence. Cancer Prev Res; 10(11); 635-40. ©2017 AACR.

Gene methylation biomarkers in sputum as a classifier for lung cancer risk.

CT screening for lung cancer reduces mortality, but will cost Medicare ∼2 billion dollars due in part to high false positive rates. Molecular biomarkers could augment current risk stratification used to select smokers for screening. Gene methylation in sputum reflects lung field cancerization that remains in lung cancer patients post-resection. This population was used in conjunction with cancer-free smokers to evaluate classification accuracy of a validated eight-gene methylation panel in sputum for cancer risk. Sputum from resected lung cancer patients (n=487) and smokers from Lovelace (n=1380) and PLuSS (n=718) cohorts was studied for methylation of an 8-gene panel. Area under a receiver operating characteristic curve was calculated to assess the prediction performance in logistic regressions with different sets of variables. The prevalence for methylation of all genes was significantly increased in the ECOG-ACRIN patients compared to cancer-free smokers as evident by elevated odds ratios that ranged from 1.6 to 8.9. The gene methylation panel showed lung cancer prediction accuracy of 82-86% and with addition of clinical variables improved to 87-90%. With sensitivity at 95%, specificity increased from 25% to 54% comparing clinical variables alone to their inclusion with methylation. The addition of methylation biomarkers to clinical variables would reduce false positive screens by ruling out one-third of smokers eligible for CT screening and could increase cancer detection rates through expanding risk assessment criteria.

The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases.

INTRODUCTION: The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin-stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise κ scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC. METHODS: Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3). RESULTS: For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, κ scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64. CONCLUSIONS: Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided.

Superficial soft-tissue masses of the extremities.

Superficial soft-tissue masses are among the most common indications for imaging of the extremities. A broad array of benign and malignant processes may be manifested in palpable cutaneous or subcutaneous masses or nodules. Most such lesions are treated with surgical excision, but some may be conservatively managed. The lesions can be differentiated according to their location in one or more skin layers (epidermis, dermis, and subcutis), their histologic composition, and the associated anatomic abnormality or disease process. Because the imaging characteristics of many benign soft-tissue lesions overlap with those of malignant ones, knowledge of the patient's clinical history (including any laboratory test results) and direct visual examination of the lesion often are important for differentiation. Histologic analysis may be necessary to achieve a definitive diagnosis.

Fine-needle aspiration cytology of alveolar rhabdomyosarcoma utilizing ThinPrep liquid-based sample and cytospin preparations: a case confirmed by FKHR break apart rearrangement by FISH probe.

Rhabdomyosarcoma is the most common childhood sarcoma that occurs in the soft tissues of the head and neck, genitourinary system, and extremities. While this tumor may also be seen in young adults, it is distinctly unusual to see this neoplasm beyond the fifth decade. The use of fluorescence in situ hybridization (FISH) probes on fine-needle aspiration material for chromosomal analysis to detect chromosomal translocations are not well established. Herein we present a case of metastatic alveolar rhabdomyosarcoma originating in the nasal sinus and recurring in the neck of an adult man 5 yr after his initial presentation. The ThinPrep smear demonstrated isolated malignant tumor cells similar to his previous histologic material. The cytologic findings of alveolar rhabdomyosarcoma were confirmed utilizing a dual color break apart FISH probe which identified the FKHR translocation on the cytospin preparation prepared from a ThinPrep vial and processed as a cytospin preparation. In addition to routine and immunocytologic staining, we demonstrate that aspirated tumor cells can be analyzed using a FISH probe to identify specific chromosomal abnormalities.

Leiomyoma of deep soft tissue mimicking calcific myonecrosis.

Leiomyoma of deep soft tissue is an unusual entity reported in less than 60 cases in the English literature. The lesion is now accepted as a rare neoplasm. Leiomyomata of deep soft tissue have been divided into 2 groups, those occurring primarily in women in the retroperitoneum, histologically similar to leiomyomata of the uterus, and those occurring equally in both sexes in the somatic deep soft tissues. Irrespective of location, these lesions can demonstrate calcification, and even less commonly ossification. We report a unique case of a leiomyoma of deep soft tissue that mimicked the clinical and radiographic features of calcific myonecrosis, also a rare mass forming soft-tissue lesion. Clinical and radiographic information are often critical in the diagnosis of soft-tissue lesions; however, this case demonstrates that a lesion can deviate from the standard clinical and radiographic interpretations most commonly attributed to it.

Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial.

PURPOSE: To determine the objective response rate, duration of remission and toxicity of octreotide alone or with the later addition of prednisone in patients with unresectable, advanced thymic malignancies in whom the pretreatment octreotide scan was positive. PATIENTS AND METHODS: Forty-two patients with advanced thymoma or thymic carcinoma were entered onto the trial, of whom 38 were fully assessable (one patient had inconclusive histology; three patients had negative octreotide scan). Patients received octreotide 0.5 mg subcutaneously tid. At 2 months, patients were evaluated. Responding patients continued to receive octreotide alone; patients with progressive disease were removed from the study. All others received prednisone 0.6 mg/kg orally qid for a maximum of 1 year. RESULTS: Two complete (5.3%) and 10 partial responses (25%) were observed (four partial responses with octreotide alone; the remainder with octreotide plus prednisone). None of the six patients without pure thymoma responded. The 1- and 2-year survival rates were 86.6% and 75.7%, respectively. Patients with an Eastern Cooperative Oncology Group performance status of 0 lived significantly longer than did those with a performance status of 1 (P =.031). CONCLUSION: Octreotide alone has modest activity in patients with octreotide scan-positive thymoma. Prednisone improves the overall response rate but is associated with increased toxicity. Additional studies with the agent are warranted.

Oncoproteins and proliferation markers in synovial sarcomas: a clinicopathologic study of 19 cases.

PURPOSE: The objective of this study was to evaluate synovial sarcomas for the expression of oncogenic proteins (Her2/neu, EGFR, Bcl-2, p53) and proliferation markers (Ki-67, Topoisomerase 2alpha), as possible markers of prognostic significance. METHODS: From 17 patients with synovial sarcomas 19 tumors (15 primary, 2 recurrent, and 2 metastatic) were selected on the basis of characteristic histology, the expression of at least one epithelial marker, and/or the presence of t(X;18). Adequate follow-up was available in all cases. RESULTS: The tumors were tested immunohistochemically and were found to express multiple oncogenic proteins. Four of 19 synovial sarcomas (21%) demonstrated nuclear over-expression of p53 protein; 18 of 19 tumors (94%) stained positive for Bcl-2; and 13 of 19 tumors (68%) were immunoreactive with EGFR. Of particular interest was the frequent expression of Her2/neu, an oncogenic protein more commonly observed in epithelial neoplasms. Ten of 19 tumors (52%, 7 monophasic and 3 biphasic) showed positive cytoplasmic and membranous staining with Her2/neu (HercepTest, DAKO). The staining intensity ranged from 1+ to 2+. Cellular expression of Her2/neu was independent of EGFR positivity and showed no association with proliferative activity of the tumors. FISH analysis of eight positive cases showed no evidence of Her2/neu gene amplification. Among the non-metastatic tumors, we found a significant correlation between Ki-67 and Topoisomerase 2alpha. Spearman's correlation co-efficient was 0.86 with P=0.001 ( n=17). CONCLUSIONS: In this relatively small series of cases, we found no definite correlation between the over-expression of Her2/neu and clinical outcome. The over-expression of p53 was significantly associated with clinical outcome (Fisher's exact test, P=0.02).