Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study.

OBJECTIVES: To assess bone marrow (BM) sampling in academic medical centers. METHODS: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. RESULTS: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. CONCLUSIONS: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.

Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Celecoxib in Addition to Standard Chemotherapy for Advanced Non-Small-Cell Lung Cancer With Cyclooxygenase-2 Overexpression: CALGB 30801 (Alliance).

Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved progression-free and overall survival in patients with moderate to high COX-2 expression by immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with pleural effusion or stage IV according to American Joint Committee on Cancer [sixth edition] criteria) were preregistered, and biopsy specimens were analyzed for COX-2 by IHC. Patients with COX-2 expression ≥ 2, performance status of 0 to 2, and normal organ function were eligible. Chemotherapy was determined by histology: carboplatin plus pemetrexed for nonsquamous NSCLC and carboplatin plus gemcitabine for squamous histology. Patients were randomly assigned to celecoxib (400 mg twice per day; arm A) or placebo (arm B). The primary objective was to demonstrate improvement in progression-free survival in patients with COX-2 index ≥ 4 with hazard ratio of 0.645 with approximately 85% power at two-sided significance level of .05. Results The study was halted for futility after 312 of the planned 322 patients with COX-2 index ≥ 2 were randomly assigned. There were no significant differences between the groups (hazard ratio, 1.046 for COX-2 ≥ 4). Subset analyses evaluating histology, chemotherapy regimen, and incremental COX-2 expression did not demonstrate any advantage for COX-2 inhibition. Elevation of baseline urinary metabolite of prostaglandin E2, indicating activation of the COX-2 pathway, was a negative prognostic factor. Values above the third quartile may have been a predictive factor. Conclusion COX-2 expression by IHC failed to select patients who could benefit from selective COX-2 inhibition. Urinary metabolite of prostaglandin E2 may be able to identify patients who could benefit from COX-2 inhibition.

NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016.

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.

Basal Cell Skin Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) of the skin is the most common cancer, with a higher incidence than all other malignancies combined. Although it is rare to metastasize, patients with multiple or frequently recurring BCC can suffer substantial comorbidity and be difficult to manage. Assessment of risk is a key element of management needed to inform treatment selection. The overall management of BCC primarily consists of surgical approaches, with radiation therapy as an alternate or adjuvant option. Many superficial therapies for BCC have been explored and continue to be developed, including topicals, cryosurgery, and photodynamic therapy. Two hedgehog pathway inhibitors were recently approved by the FDA for systemic treatment of advanced and metastatic BCC, and others are in development. The NCCN Guidelines for Basal Cell Skin Cancer, published in full herein, include recommendations for selecting among the various surgical approaches based on patient-, lesion-, and disease-specific factors, as well as guidance on when to use radiation therapy, superficial therapies, and hedgehog pathway inhibitors.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016.

These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC; Versions 1-4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy.

Homogenous Good Outcome in a Heterogeneous Group of Tumors: An Institutional Series of Outcomes of Superficial Soft Tissue Sarcomas.

Introduction. Superficial soft tissue sarcomas (S-STS) are generally amenable to wide excision. We hypothesized that local recurrence (LR) should be low, even without radiation therapy (RT), and sought to examine the contribution of depth to LR and OS. Methods. Patients with S-STS were retrospectively reviewed. Demographics, tumor features, treatment received, and outcomes were analyzed. Results. 103 patients were identified. Median age was 55 years; 53% of patients were female. Tumor site was 39% in trunk, 38% in the lower extremity, 14% in the upper extremity, and 9% in other locations. The most common histology was 36% leiomyosarcoma. Median tumor size was 2.8 cm (range 0.2-14 cm). Sixty-six percent of tumors were of intermediate/high grade. RT was administered preoperatively in 6% of patients and postoperatively in 15% of patients. An R0 resection was accomplished in 92%. At a median follow-up of 34.2 months (range 2.3-176), 9 patients had a LR (8.7%). Tumor size and grade were not associated with LR. OS was not associated with any tumor or patient variables on univariate analysis. Conclusions. LR was low for S-STS, even with large or high grade tumors and selective use of RT. Surgical resection alone may be adequate therapy for most patients. Superficial location seems to supersede other factors imparting a good prognosis for this group of tumors.

Non-Small Cell Lung Cancer, Version 6.2015.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies. These NCCN Guidelines Insights describe the different testing methods currently available for determining whether patients have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations.

Non-small cell lung cancer, version 1.2015.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.

Lymphangioma circumscriptum of the vulva in a patient with Noonan syndrome.

Lymphangioma circumscriptum (LC) results from the development of abnormal lymphatic vasculature and is characterized by the presence of grouped vesicles filled with clear or colored fluid. Vulvar localization is uncommon. Abnormalities of the lymphatic system, such as lymphedema and cystic hygroma, are well-known features of genetic disorders such as Noonan syndrome (NS) and Turner syndrome. We report the case of a patient with NS who presented with LC of the vulva. We also discuss the expanding spectrum of clinical anomalies associated with the presentation of NS.

Dermatofibrosarcoma protuberans, version 1.2014.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor characterized by a relatively high risk of local recurrence and low risk of metastasis. The NCCN Guidelines for DFSP provide multidisciplinary recommendations on the management of patients with this rare disease. These NCCN Guidelines Insights highlight the addition of the Principles of Pathology section, which provides recommendations on the pathologic assessment of DFSP. Because DFSP can mimic other lesions, immunohistochemical studies are often required to establish diagnosis. Cytogenetic testing for the characteristic translocation t(17;22)(q22;q13) can also be valuable in the differential diagnosis of DFSP with other histologically similar tumors.

Merkel cell carcinoma, version 1.2014.

Merkel cell carcinoma is a rare, aggressive cutaneous tumor that combines the local recurrence rates of infiltrative nonmelanoma skin cancer with the regional and distant metastatic rates of thick melanoma. The NCCN Guidelines for Merkel Cell Carcinoma provide recommendations on the diagnosis and management of this aggressive disease based on clinical evidence and expert consensus. This version includes revisions regarding the use of PET/CT imaging and the addition of a new section on the principles of pathology to provide guidance on the analysis, interpretation, and reporting of pathology results.

Giant keratoacanthoma: case report and review of the English literature.

The giant keratoacanthoma (KA) is a rare variant of KA with a maximum size exceeding 2-3 cm. Like other forms of KA, it has a tendency to spontaneously regress but can cause significant anatomic damage. A 69-year-old male presented to our hospital with a giant KA of the nose that showed complete pathological regression by the time of surgery. Pathology showed dermal scar with keratin granulomas extending through the nasal wall to the respiratory mucosa. A total of 57 similar cases from the English literature were reviewed for comparison. Few provide similar details of histological regression. Literature cases occurred predominately in males (74.1%) with a mean age of 59 years. Head tumors were most common (70.7%) and most were treated by surgery (34.5%) or a combination of surgery and radiotherapy (24.1%). Other treatment modalities reported include methotrexate, 5-fluorouracil, and interferon.

Non-small cell lung cancer, version 2.2013.

These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.

Thymomas and thymic carcinomas: Clinical Practice Guidelines in Oncology.

Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.

Non-small cell lung cancer.

Most patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.

Inflammatory myofibroblastic tumor of the mesentery: a clinical dilemma.

Although rare, extra-pulmonary inflammatory myofibroblastic tumors (IMTs) are becoming increasingly recognized. While surgical resection is currently an effective and accepted treatment for IMTs, the optimal management of unresectable or residual IMTs remains a clinical dilemma. We present the case of an incompletely resected IMT treated successfully with anti-inflammatory therapy alone, and describe the rationale for this approach.

ERBB2 juxtamembrane domain (trastuzumab binding site) gene mutation is a rare event in invasive breast cancers overexpressing the ERBB2 gene.

The recent development of targeted therapies using monoclonal antibodies has added new dimensions to breast cancer treatment. Trastuzumab has been added to the regimens that contain chemotherapeutic agents, which has improved the clinical outcomes of patients in both the adjuvant and metastatic settings. However, trastuzumab resistance, both de novo and acquired, continues to be problematic. There have been scattered studies reporting ERBB2 gene mutation, but nothing is currently known about the ERBB2 binding site mutations. In the current study, we examined the ERBB2 juxtamembrane domain trastuzumab binding site for mutations in invasive breast cancers overexpressing ERBB2. Pure tumor cells of 54 breast cancer patients were procured using laser capture microdissection. Two polymerase chain reaction primer pairs were designed to amplify the trastuzumab binding site sequence. The polymerase chain reaction product was sequenced. Standard clinicopathological data were recorded. For the 54 patients, there was one (2%) case that showed missense point mutation in exon 17 (H559A). There were nine patients treated with trastuzumab in the metastatic setting, none of which had gene mutation. Therefore, we conclude that ERBB2 juxtamembrane domain (trastuzumab binding site) gene mutation is a rare event in breast cancer. Although it is unclear whether this substitution would result in trastuzumab target therapy resistance, this would not account for the relatively high frequency of this resistance encountered clinically.

Tumour eosinophilia combined with an immunohistochemistry panel is useful in the differentiation of type B3 thymoma from thymic carcinoma.

It is sometimes difficult to differentiate between type B3 thymoma from thymic carcinoma histologically. Given the rarity of these tumours, studies have been limited. A series of 66 thymic neoplasms were reviewed and classified according to the World Health Organization (WHO) scheme. We performed a tissue microarray analysis of surgically resected thymic tumour specimens including 12 thymic carcinomas, 17 type B3 thymomas and 37 thymomas of other types. Percentage and staining intensity of immunohistochemical markers were recorded. Tumour eosinophilia was recorded positive if at least one eosinophilic cell identified. Positive staining of the following markers significantly differentiated type B3 thymoma from thymic carcinoma: cytokeratin 5/6 (15 vs. 3), Mesothelin (0 vs. 5), cytoplasmic androgen receptor (10 vs. 0), CD57 (9 vs. 0), CD5 (0 vs. 7), TdT (lymphocytic) (14 vs. 1), CD1a (lymphocytic) (14 vs. 2), CD117 (1 vs. 9), MOC31 (2 vs. 6), p21 (2 vs. 8), cytoplasmic Survivin (0 vs. 4), and tumour eosinophilia (1 vs. 11). Combining two or three markers was able to differentiate these two tumours with area under the curve percentage of at least 92%. Tumour eosinophilia combined with a panel of immunohistochemistry could differentiate type B3 thymoma from thymic carcinoma.