Intrapulmonary Nodes Research Articles

Improving the pathologic evaluation of lung cancer resection specimens.

Accurate post-operative prognostication and management heavily depend on pathologic nodal stage. Patients with nodal metastasis benefit from post-operative adjuvant chemotherapy, those with mediastinal nodal involvement may also benefit from adjuvant radiation therapy. However, the quality of pathologic nodal staging varies significantly, with major survival implications in large populations of patients. We describe the quality gap in pathologic nodal staging, and provide evidence of its potential reversibility by targeted corrective interventions. One intervention, designed to improve the surgical lymphadenectomy, specimen labeling, and secure transfer between the operating theatre and the pathology laboratory, involves use of pre-labeled specimen collection kits. Another intervention involves application of an improved method of gross dissection of lung resection specimens, to reduce the inadvertent loss of intrapulmonary lymph nodes to histologic examination for metastasis. These corrective interventions are the subject of a regional dissemination and implementation project in diverse healthcare systems in a tri-state region of the United States with some of the highest lung cancer incidence and mortality rates. We discuss the potential of these interventions to significantly improve the accuracy of pathologic nodal staging, risk stratification, and the quality of specimens available for development of stage-independent prognostic markers in lung cancer.

Lymph node metastasis in clinical stage IA peripheral lung cancer.

To investigate lymph node metastasis especially the intrapulmonary node in clinical IA peripheral lung cancer patients to evaluate the indications for lung segmentectomy in lymph node level. Patients (n=292) with clinical stage IA peripheral lung cancer received radical lobectomy at our department between October 2013 and July 2014 were enrolled in our study. Lymph nodes were obtained during routine surgical procedures while segmental lymph nodes were dissected from the resected lobe for pathological examination. New classification for pulmonary adenocarcinoma with each histologic component was also analyzed. The percentage of patients found to have no lymph node metastasis was 90.4% (264/292). Tumor size on computed tomography and tumor consistency were independent predictors for lymph node metastasis. Tumor with a dominant ground-glass opacity (GGO) component was a good predictor for lymph node metastasis (p<0.001). Metastasis was more common in larger tumors (p<0.001), but there was non-tumor bearing segment metastasis even in tumor less than 1cm. Patients with micropapillary or solid component were correlated with lymph node metastasis (p=0.001 and p=0.009, respectively). The rate of metastasis to the lymph nodes is very low in clinical stage IA peripheral lung cancer patients. Patients with a dominant GGO component on CT might be the suitable candidates for lung segmentectomy because of almost no lymph node metastasis. Careful selection should be made for the patients with tumor size ≤2 cm who had metastasized nodes in non-tumor bearing segment when considering segmentectomy. If the resected tumor had micropapillary or solid component, the lobectomy might be considered.

The incidental pulmonary nodule in a child. Part 1: recommendations from the SPR Thoracic Imaging Committee regarding characterization, significance and follow-up.

No guidelines are in place for the follow-up and management of pulmonary nodules that are incidentally detected on CT in the pediatric population. The Fleischner guidelines, which were developed for the older adult population, do not apply to children. This review summarizes the evidence collected by the Society for Pediatric Radiology (SPR) Thoracic Imaging Committee in its attempt to develop pediatric-specific guidelines.Small pulmonary opacities can be characterized as linear or as ground-glass or solid nodules. Linear opacities and ground-glass nodules are extremely unlikely to represent an early primary or metastatic malignancy in a child. In our review, we found a virtual absence of reported cases of a primary pulmonary malignancy presenting as an incidentally detected small lung nodule on CT in a healthy immune-competent child.Because of the lack of definitive information on the clinical significance of small lung nodules that are incidentally detected on CT in children, the management of those that do not have the typical characteristics of an intrapulmonary lymph node should be dictated by the clinical history as to possible exposure to infectious agents, the presence of an occult immunodeficiency, the much higher likelihood that the nodule represents a metastasis than a primary lung tumor, and ultimately the individual preference of the child's caregiver. Nodules appearing in children with a history of immune deficiency, malignancy or congenital pulmonary airway malformation should not be considered incidental, and their workup should be dictated by the natural history of these underlying conditions.

Imaging features of thoracic metastases from gynecologic neoplasms.

Gynecologic malignancies are a heterogeneous group of common neoplasms and represent the fourth most common malignancy in women. Thoracic metastases exhibit various imaging patterns and are usually associated with locally invasive primary neoplasms with intra-abdominal spread. However, thoracic involvement may also occur many months to years after initial diagnosis or as an isolated finding in patients without evidence of intra-abdominal neoplastic involvement. Thoracic metastases from endometrial carcinoma typically manifest as pulmonary nodules and lymphadenopathy. Thoracic metastases from ovarian cancer often manifest with small pleural effusions and subtle pleural nodules. Thoracic metastases to the lungs, lymph nodes, and pleura may also exhibit calcification and mimic granulomatous disease. Metastases from fallopian tube carcinomas exhibit imaging features identical to those of ovarian cancers. Most cervical cancers are of squamous histology, and while solid pulmonary metastases are more common, cavitary metastases occur with some frequency. Metastatic choriocarcinoma to the lung characteristically manifests with solid pulmonary nodules. Some pulmonary metastases from gynecologic malignancies exhibit characteristic features such as cavitation (in squamous cell cervical cancer) and the "halo" sign (in hemorrhagic metastatic choriocarcinoma) at computed tomography (CT). However, metastases from common gynecologic malignancies may be subtle and indolent and may mimic benign conditions such as intrapulmonary lymph nodes and remote granulomatous disease. Therefore, radiologists should consider the presence of locoregional disease as well as elevated tumor marker levels when interpreting imaging studies because subtle imaging findings may represent metastatic disease. Positron emission tomography/CT may be helpful in identifying early locoregional and distant tumor spread.

66IN - Optimal Assessment of an Additional Lung Nodule in a Patient with Potential for Cure

ABSTRACT A significant number of patients present with a dominant pulmonary mass or presumptive lung cancer with an additional radiologically visible intra-pulmonary nodule. The IASLC stage classification of T3 (nodule within same lobe), T4 (nodule within other ipsilateral lobe) and M1a (contralateral nodule) is applied for these patients. It is very difficult to say what the frequency is of early lung cancer with an additional pulmonary nodule. Several studies estimated the prevalence of an additional nodule coexisting with potentially operable lung cancer on imaging between 20 and 25% of patients, in whom 25-30% is malignant. Additional nodules account for only 2.5% of cases included in the 7th edition of the IASLC staging database. It is unclear what proportion is grossly detectable instead of only pathologically reported. In addition, the T3/T4/M1a additional nodule stage classification should not be applied to synchronous second primary lung cancers (SPLC) or lesions that are imaged but most likely benign such as subcentimeter intrapulmonary lymph nodes. The distinction between synchronous SPLC and intrapulmonary metastatic disease has relied upon Martini and Melamed's approach. More recently, the hypothesis of field cancerization in the lung has made acceptance of synchronous SPLC easier. Additional nodules judged as synchronous SPLC should be staged with separate TNM designations. Patients with an additional lung nodule should be evaluated by an experienced multidisciplinary tumour board. The biological relationships between the lesions does matter in terms of our traditional thinking around staging and therapy. A careful evaluation for distant and mediastinal metastases is strongly recommended. The evaluation for possible extrathoracic metastases should be carried out by an integrated PET/CT and brain MRI/CT. In the absence of extrathoracic distant metastases, an invasive mediastinal evaluation either by mediastinoscopy or endosonography should be carried out. No further invasive diagnostic workup of the T3 or T4 additional nodule is undertaken for an operable patient. Patients unable or equivocal to undergo a contralateral surgical resection should undergo an endoscopic or percutaneous biopsy of the M1a additional nodule. Disclosure: The author has declared no conflicts of interest.

The impact of a novel lung gross dissection protocol on intrapulmonary lymph node (LN) retrieval from lung cancer (LC) resection specimens.

7571 Background: Although thorough pathologic LN staging provides the greatest prognostic information in patients with potentially curable non-small cell LC, N1 nodal metastases are frequently miss...

The impact of a novel lung gross dissection protocol on intrapulmonary lymph node retrieval from lung cancer resection specimens.

Although thorough pathologic nodal staging provides the greatest prognostic information in patients with potentially curable non-small cell lung cancer, N1 nodal metastasis is frequently missed. We tested the impact of corrective intervention with a novel pathology gross dissection protocol on intrapulmonary lymph node retrieval. This study is a retrospective review of consecutive lobectomy, or greater, lung resection specimens over a period of 15 months before and 15 months after training pathologist's assistants on the novel dissection protocol. One hundred forty one specimens were examined before and 121 specimens after introduction of the novel dissection protocol. The median number of intrapulmonary lymph nodes retrieved increased from 2 to 5 (P<.0001), and the 75th to 100th percentile range of detected intrapulmonary lymph node metastasis increased from 0 to 5 to 0 to 17 (P=.0003). In multivariate analysis, the extent of resection, examination period (preintervention or postintervention), and pathologic N1 (vs N0) status were most strongly associated with a higher number of intrapulmonary lymph nodes examined. A novel pathology dissection protocol is a feasible and effective means of improving the retrieval of intrapulmonary lymph nodes for examination. Further studies to enhance dissemination and implementation of this novel pathology dissection protocol are warranted.

Intrapulmonary lymph node: a common and underrecognized tomography finding

We read with great interest the well-written manuscript by Melo et al.,(1) who analyzed clinical and radiological findings that influence the pathological diagnosis of solitary pulmonary nodule (SPN). They concluded that advanced age, greater maximum SPN diameter, and spiculated margins were significantly associated with the diagnosis of malignancy. For radiologists and pulmonologists, SPNs continue to represent a major diagnostic challenge. Recent technological advances in imaging techniques and the widespread use of CT have increased the frequency of pulmonary nodule detection.(2) Small nodules (1-2 mm in diameter) are commonly detected on CT images, and their clinical importance appears to differ markedly from that of larger nodules identified on chest X-rays.(2) Thus, this enhanced detection has not affected the basic issue of distinguishing the status of a nodule, whether benign (requiring no specific approach) or indeterminate (potentially malignant),(2) and most nodules are resected for diagnosis and determination of the appropriate treatment.(3) Pulmonary lymph nodes are a common and underrecognized cause of a peripheral SPN. These lymph nodes are usually found at the bifurcation of the bronchi, before the fourth branch, where they are referred to as peribronchial lymph nodes. Lymph nodes are occasionally present within the lung parenchyma, where they are designated intrapulmonary lymph nodes (IPLNs)(3) or perifissural nodules (PFNs). The differentiation of IPLNs from other small pulmonary nodules on CT images is difficult although clinically important. In particular, the misinterpretation of a radiologically detected IPLN as a separate tumor nodule leads to overstaging and possible exclusion from indication for surgical treatment in patients with primary lung cancer. (3) Several tomographic characteristics may aid in the differential diagnosis of an IPLN (Figure 1). These lymph nodes are oval, round, triangular, or trapezoidal, with sharply defined borders; they are almost always located below the level of the carina, predominantly in the subpleural regions of the lower lobes. They are frequently attached to the pleura or separated from the pleural surface by a few millimeters.(3-5) IPLNs have thin linear attachments extending from the nodule to the pleura. These linear densities have been shown to represent ectatic lymphatic channels.(5) De Hoop et al.(6) recently reported that the growth rates of PFNs can reach those of malignant nodules, but no PFN in their study was malignant. In conclusion, IPLNs are benign features that should be taken into consideration in the differential diagnosis of an SPN. Their identification might reduce the number of unnecessary surgeries and follow-up examinations.

Lymphoproliferative Lung Disorders: A Radiologic-Pathologic Overview. Part I: Reactive disorders

Lymphoid tissue is a normal component of the lung and manifests as intrapulmonary lymph nodes, bronchus-associated lymphoid tissue (BALT), peripheral lymphocytic aggregates, solitary lymphocytes, and phagocytic cells. Pulmonary lymphoid lesions are thought to develop as a consequence of anomalous stimulation and response of the bronchus-associated lymphoid tissue and manifests as a spectrum of lymphoproliferative disorders that may be reactive or neoplastic. Reactive disorders are polyclonal abnormalities and include nodular lymphoid hyperplasia, lymphocytic interstitial pneumonia, follicular bronchiolitis, angiofollicular hyperplasia, and enlarged intrapulmonary lymph nodes. Affected patients are often asymptomatic. Imaging findings include focal nodules, diffuse bilateral centrilobular nodules, and hilar or mediastinal masses.

Evaluation of endobronchial ultrasound‐guided fine‐needle aspirations (EBUS‐FNA): Correlation with adequacy and histologic follow‐up

Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) is a minimally invasive modality for diagnosing mediastinal lesions. When determining adequacy, EBUS-FNAs are evaluated for diagnostic material or sufficient lymphoid tissue. In this study, the authors evaluated their experience with EBUS-FNAs and correlated the findings with adequacy and histologic follow-up. EBUS-FNAs were retrospectively reviewed over a 3-year period and correlated with the clinicopathologic findings, adequacy, and histologic follow-up. In total, 593 EBUS-FNAs were obtained from 356 patients, including 420 (71%) satisfactory (SAT) cases, 107 (18%) less than optimal (LTO) cases, and 66 (11%) unsatisfactory (UNSAT) cases. The overall diagnostic yield was 71%, and the mediastinal (N2) lymph nodes had better yield (72%) than the peripheral intrapulmonary and hilar (N1) lymph nodes (64%). Histologic follow-up was available in 203 cases (34%), and malignancy was identified in 7 UNSAT cases (23%), 6 LTO-negative cases (11%), and 4 SAT cases (3%) with a negative cytologic diagnosis. In the suboptimal cases with follow-up, 79% were benign and 21% were malignant on follow-up, including 25 (14%) with fibrosis or hyalinization. The sensitivity, specificity, and positive and negative predictive values in the study were 80%, 100%, 100%, and 95%, respectively. The current data demonstrated that EBUS-FNA has good sensitivity, high specificity, and a higher diagnostic yield for N2 lymph nodes compared with N1 lymph nodes. The data also illustrate the finding that suboptimal cases have a greater risk of false-negative diagnoses and a 21% chance of malignancy, including processes with fibrosis or hyalinization.

Surgical approaches of endobronchial neoplasms.

Endobronchial tumors are a rare entity that presents with different pathological findings. The interventional pulmonologist, but also the thoracic surgeon have at their disposal the same techniques for diagnosis, however; the two modalities differentiate in the treatment approach. Diagnosis evaluation should include lymph node evaluation. Minimal invasive techniques under local or general anesthesia are usually preferred by the interventional pulmonologists, whereas in the surgical approach of the thoracic surgeons the general anesthesia is necessary. A more extensive surgical approach either lobotomy or pneumonectomy should be performed in cases with positive intrapulmonary lymph nodes. Carinal reconstruction should be performed skillfully to get a negative proximal margin whenever needed. In the current manuscript we will present the methods of patient evaluation and surgical techniques for the management of these lesions.

Response to editorial titled 'Intrapulmonary lymph node retrieval: unclear benefit for aggressive pathologic dissection'.

Response to editorial titled 'Intrapulmonary lymph node retrieval: unclear benefit for aggressive pathologic dissection'.

Response to: intrapulmonary lymph node retrieval.

To the editor, The heterogenous non-small cell lung cancer (NSCLC) patient population harboring N1 metastatic disease provides both diagnostic and treatment challenges. The wide range of 5-year overall survival (OS) for this diverse group, from 27-67%, clearly illustrates the need for better prognostic, diagnostic and/or treatment modalities (1). Successful nodal staging is a variable greatly influenced by clinician, surgeon and pathologist to identify, resect and interpret. How we achieve this is evolving. Metastasis to mediastinal lymph nodes (LNs), N2 or N3, clearly impacts candidacy for curative intent resections. It is, however, involvement of N1 nodes and their impact in clinically resectable disease that shapes our current discussion. Recently, Ramirez et al. demonstrated improvement in nodal sampling of N1 nodes, identifying an additional 514 LNs in 374 patients, utilizing a more aggressive intrapulmonary staging technique following traditional pathologic staging. Their article “Incomplete Intrapulmonary Lymph Node Retrieval After Routine Pathologic Examination of Resected Lung Cancer” also demonstrated upstaging in 8 of 73 patients based on this technique (2). Data suggests that a greater number of N1 positive nodes impacts survival (3). Although our staging system is not based on quantity, rather presence of metastasis within a LN station, a growing body of literature is examining the impact of the number of LN metastasis (4). Further studies to evaluate the impact of this technique on patient outcomes are needed. The authors comment on an upcoming study designed to address the upstaging rate and relapse free survival achieved through more thorough intrapulmonary dissection of N1 nodes, citing a recently published case control study where improved mediastinal (N2 and N3) nodal staging utilizing their surgical collection kit was obtained (5).

Discriminative features of thin-slice computed tomography for peripheral intrapulmonary lymph nodes

The use of computed tomography (CT) scans has increased the opportunities to detect small nodular shadows in peripheral lung fields. Intrapulmonary lymph nodes (IPLNs) are sometimes identified among these nodular shadows, and a differential diagnosis is often difficult. However, few descriptions of the CT findings of IPLNs, with regard to their potential for the differential diagnosis of lung cancer, have been published. From 2006 through 2011, 606 patients underwent thoracic surgery for pulmonary nodules. Nine patients (1.5%) had pathologically diagnosed IPLNs. We retrospectively reviewed the clinicopathological features and thin-section CT findings of the patients with IPLNs. We also compared these IPLN patients with 17 patients having small-sized lung cancer. In six cases, the nodules were round, and linear density extending from the IPLNs was visualized in seven nodules. The nodules in IPLNs were located in the lower lobe, and the nodule borders were clearer than those of lung cancers. Six out of nine nodules were round, and linear densities were more easily visualized for the IPLNs. Medical specialists need to be familiar with the discriminative features of thin-slice CT for IPLNs not only to avoid performing unnecessary operations, but also to prevent the mis-staging of lung cancer.

Incomplete intrapulmonary lymph node retrieval after routine pathologic examination of resected lung cancer.

In their paper entitled “Incomplete Intrapulmonary Lymph Node Retrieval After Routine Pathologic Examination of Resected Lung Cancer” (1), R A. Ramirez and colleagues advocate a special pathologic examination (SPE) protocol for dissection and examination of lung resection specimens in order to make an inventory as complete as possible of lymph nodes (LN) removed with the resected lung.

Unicentric Castleman's Disease Arising from an Intrapulmonary Lymph Node.

Castleman's disease is an uncommon lymphoproliferative disorder of unknown etiology, most often involving the mediastinum. It has 2 distinct clinical forms: unicentric and multicentric. Unicentric Castleman's disease arising from an intrapulmonary lymph node is rare, and establishing a preoperative diagnosis of this disease is very difficult mainly due to a lack of specific imaging features. We report a case of intrapulmonary unicentric Castleman's disease in an asymptomatic 19-year-old male patient who was accurately diagnosed by preoperative computed tomography (CT). The mass was incidentally found on a routine chest X-ray. A subsequent dynamic CT showed a well-defined, hypervascular, soft-tissue mass with small calcifications located in the perihilar area of the right lower lung. Three-dimensional CT (3D-CT) angiography indicated that the mass was receiving its blood supply through a vascular network at its surface that originated from 2 right bronchial arteries. The clinical history and CT findings were consistent with a diagnosis of unicentric Castleman's disease, and we safely and successfully removed the tumor via video-assisted thoracoscopic surgical lobectomy. This case shows that the imaging characteristics of these rare tumors on contrast-enhanced CT combined with 3D-CT angiography can be helpful in reliably establishing a correct preoperative diagnosis.

Intrapulmonary lymph nodes: computed tomography findings with histopathologic correlations

We retrospectively assessed the computed tomography (CT) features of 31 intrapulmonary lymph nodes (IPLNs) with histopathologic correlations. CT scans revealed that the IPLNs are located in the subpleural region, frequently below the level of the carina, and angular in shape. Most of the IPLNs are solid in texture but occasionally present with a ground-glass appearance. For pleura-attached and pleura-separated IPLNs, one or more and 3 or more linear opacities extending from the nodules can be identified, respectively. Histologically, the IPLNs are located either at the junction of the pleura and lung lobules or at the junction of adjacent lung lobules.

Intrapulmonary lymph node retrieval: unclear benefit for aggressive pathologic dissection.

Lymph node (LN) status is a highly significant component of staging non-small cell lung cancer (NSCLC). Staging of NSCLC provides prognostic data related to risk of recurrence as well as overall survival (1). Lymph node metastasis alters treatment decisions, including surgical resectability and appropriateness of adjuvant interventions. Current pathologic LN sampling techniques often evaluate a low number of LNs (2-4). Goals of current staging techniques include sampling at minimum three N1 (hilar) nodes examined in settings of resectable disease (5). Patients harboring N1 metastatic disease are a heterogeneous group with a calculated 5 year overall survival (OS) of 38% (1) with widely variable range from 27-67% (1,6,7).

Incomplete Intrapulmonary Lymph Node Retrieval After Routine Pathologic Examination of Resected Lung Cancer

Pathologic nodal stage affects prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). Unlike examination of mediastinal lymph nodes (LNs), which depends on surgical practice, accurate examination of intrapulmonary (N1) nodes depends primarily on pathology practice. We investigated the completeness of N1 LN examination in NSCLC resection specimens and its potential impact on stage. We performed a case-control study of a special pathologic examination (SPE) protocol using thin gross dissection with retrieval and microscopic examination of all LN-like material on remnant NSCLC resection specimens after routine pathologic examination (RPE). We compared LNs retrieved by the SPE protocol with nodes examined after RPE of the same lung specimens and with those of an external control cohort. We retrieved additional LNs in 66 (90%) of 73 patient cases and discovered metastasis in 56 (11%) of 514 retrieved LNs from 27% of all patients. We found unexpected LN metastasis in six (12%) of 50 node-negative patients. Three other patients had undetected satellite metastatic nodules. Pathologic stage was upgraded in eight (11%) of 73 patients. The time required for the SPE protocol decreased significantly with experience, with no change in the number of LNs found. Standard pathology practice frequently leaves large numbers of N1 LNs unexamined, a clinically significant proportion of which harbor metastasis. By improving N1 LN examination, SPE can have an impact on prognosis and adjuvant management. We suggest adoption of the SPE to improve pathologic staging of resected NSCLC.

Size distribution and metastasis in discarded intrapulmonary lymph nodes (LN) after lung cancer resection.

7072^ Background: Lymph node (LN) status is the most important prognostic determinant after resection of lung cancer. 18% of a SEER cohort and 12% of a Memphis cohort had no LNs examined (pNx). Patients with pNx have inferior survival to T-category matched pN0 patients with at least 1 LN examined. The optimal number of LN needed to safely declare a patient pN0 may be &gt;10. Less than 20% of resections in SEER achieve this. We hypothesized that a significant number of intrapulmonary LNs are left unexamined and some may harbor metastatic disease. We report the size characteristics of materials examined in a re-dissection protocol to test this hypothesis. Methods: Prospective study of lung resection specimens re-dissected after signout of the final pathology report. Remnant lung material was dissected with thin cuts and all LN-like material was retrieved for microscopic examination, irrespective of size or location. The size of non-LN tissue, LN without metastasis and LN with metastases were compared using the Wilcoxon-Mann-Whitney test. Results: 112 specimens were examined and 1,094 LN-like materials were retrieved. 749 (69%) proved to be LN tissue. 71 (10%) LNs retrieved had metastasis. Non-LN tissue was significantly smaller than LN tissue (p&lt;0.0001). LNs with metastasis were significantly larger than those without metastasis (p &lt;0.0001). 60% of materials &gt;2cm were LNs with metastasis. 7% of materials &lt;1cm were LN with metastasis. 52% of LNs with metastasis, and 55% of LNs without metastasis measured from 0.5 to 1.5cm (Table). Majority of LNs &gt;2cm had metastatic disease, but 40% did not; a notable proportion of LNs with metastasis were small. Nearly equal percentages of LNs with and without metastasis were found in the range of 0.5-1.5cm. Conclusions: Statistical differences in size between lymph nodes with and without metastasis is clinically meaningless due to broad overlap. LN size alone is not an adequate predictor of LN metastasis. [Table: see text]