Size and histologic characteristics of lymph node material retrieved from tissue discarded after routine pathologic examination of lung cancer resection specimens.

Redissection of discarded lung resection specimens after routine pathology examination reveals missed lymph node metastasis. We sought to determine if size can be used to grossly select lymph nodes for microscopic examination. This is a prospective cohort study of lymph nodes retrieved from discarded lung resection specimens. The association between size and histologic characteristics of retrieved material was compared by the Wilcoxon-Mann-Whitney test. We retrieved 1094 grossly 'lymph node-like" tissue from 112 remnant lung resection specimens, of which 345 (32%) proved not to be lymph nodes and 71 (9%) of 749 lymph nodes had metastasis. Metastasis was present in discarded nodes in 26 (23%) of 112 patients. The non-lymph node tissue was significantly smaller than lymph nodes (P < .0001); lymph nodes with metastases were significantly larger than those without metastases (P < .0001). However, there was significant size overlap between the 3 types of grossly lymph node-like tissue. Thirty-two percent of nodes with metastasis were less than 1 cm; 15% of patients had at least 1 lymph node less than 1 cm with metastasis. The size difference between lymph nodes with and without metastasis is clinically unhelpful because of broad overlap. Size is insufficiently discriminatory and cannot be relied on to select materials for histologic examination. A third of grossly retrieved material was non-lymph node tissue. This probably occurs during routine pathologic examination and likely contributes to the low N1 lymph node count.

An unusual case of interstitial lung disease in a patient with cardiopulmonary syndrome as the initial presentation of Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a very rare disorder with only approximately 600 cases reported in the literature. ECD has been recently reclassified as a histiocytic dendritic cell neoplasm. The clinical spectrum ranges from asymptomatic tissue accumulation of histiocytes to invasive tissue infiltration, which can cause fulminant multisystem failure. It typically presents with bone pain and constitutional symptoms. Extraosseous manifestations are not uncommon. ECD-associated interstitial lung disease has been described in 20%-35% of patients. Diagnosis is primarily by tissue biopsy and immunohistochemistry showing xanthogranulomas composed of foamy histiocytes that stain positive for CD68, CD14 and CD163 and negative for CD1á and langerin. We report a case of ECD in a young man with cardiopulmonary involvement who presented with haemoptysis and dyspnoea.

Missed Intrapulmonary Lymph Node Metastasis and Survival After Resection of Non-Small Cell Lung Cancer.

BACKGROUND: Pathologic nodal stage is a key prognostic factor for patients with surgically resected lung cancer. We previously described the extent of missed intrapulmonary nodal metastasis in a cohort of patients treated at institutions in metropolitan Memphis, TN. With long-term follow-up, we now quantify the survival impact of missed nodal metastasis. METHODS: We conducted a prospective cohort study to evaluate inadvertently discarded lymph nodes in re-dissected remnant lung resection specimens from lung cancer patients. Retrieved material was histologically examined and classified as lymph nodes with and without metastasis. Survival information was obtained from hospital cancer registries. We plotted survival distributions with the use of the Kaplan-Meier method and evaluated them with proportional hazards models that controlled for important demographic and clinical factors. RESULTS: The study included 110 patients who were 54% women and 69% white. Discarded lymph nodes with metastasis were found in 25 patients (23%). Patients with missed lymph node metastasis had an increased risk of death with an unadjusted hazard ratio of 2.0 (p = 0.06) and an adjusted hazard ratio of 1.4 (p = 0.45) compared with patients without missed lymph node metastasis. Patients with more than 2 missed lymph nodes with metastasis had 4.8 times the hazard of death (p = 0.0005) compared with patients without missed lymph node metastasis (adjusted hazard ratio 6.5, p = 0.0001). CONCLUSIONS: Metastasis to inadvertently discarded intrapulmonary lymph nodes from lung cancer resection specimens was associated with reduced survival. A more rigorous gross dissection protocol for lung cancer resection specimens may provide prognostically useful information.

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.

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

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Pathologic lymph node staging practice and stage-predicted survival after resection of lung cancer.

BACKGROUND: Lymph node status is the most important prognostic factor in resectable nonsmall-cell lung cancer (NSCLC). We examined the relationship between the pattern of lymph node examination (including the number and anatomic location of resected lymph nodes), pathologic nodal stage, and survival after NSCLC resection. METHODS: Retrospective review of all NSCLC resections in the Memphis Metropolitan Area from January 1, 2004, to December 31, 2007. RESULTS: In 656 resections, the number of lymph nodes examined differed significantly between patients grouped by pathologic nodal stage (p<0.0001) and extent of resection (p<0.001). Thirty-seven percent of "mediastinal node-negative" patients had no mediastinal lymph nodes examined. Patients with pN1 and no mediastinal lymph node examination had better [corrected] survival than patients with mediastinal lymph node examination (p < 0.02) . Approximately 10% of patients with pN0 and pN2 disease had no hilar/intrapulmonary lymph nodes examined. CONCLUSIONS: Suboptimal lymph node staging was prevalent in this cohort. Large proportions of pN1 and pN0 patients were probably understaged. In patients with pathologic positive pulmonary/hilar lymph nodes, mediastinal lymph node examination was associated with poorer survival [corrected]. Interventions are needed to improve lymph node staging of NSCLC.

Outcome of surgical resection for pathologic N0 and Nx non-small cell lung cancer.

PURPOSE: Metastasis to lymph nodes (LNs) connotes poor prognosis in non-small cell lung cancer (NSCLC). Sufficient LNs must be examined to accurately determine LN negativity. Patients with no LNs examined (pNx) have an indeterminate stage, may have undetected disease and erroneous assignment to a low-risk group. To evaluate this possibility, we compared the survival of patients with node-negative disease and at least one LN examined (pN0) to those with pNx. METHODS: Retrospective analysis of all resections for NSCLC from January 1, 2004 to December 31, 2007 at hospitals in the Memphis Metropolitan Area. RESULTS: Of 746 resections, 90 (12.1%) were Nx; 506 (67.8%) N0. Demographic and histologic characteristics were similar. A total of 54.4% Nx patients had sublobar resection, compared with 5.5% N0 (p < 0.0001). In the N0 cohort, the median (range) number of LNs was 5 (1-45); N1 LNs, 3 (0-38); N2 LNs, 1 (0-29); 35.4% had no mediastinal LNs examined; 9.1% had only mediastinal LNs. Eighty- five percent of N0 patients had less than 10 LNs. The 3-year survival estimate for the T1NxM0 versus T1N0M0 patients was 70% versus 79% (p = 0.17); for T2NxM0 versus T2N0M0, it was 25% versus 65% (p < 0.01). CONCLUSIONS: A high percentage of patients undergoing surgical resection for NSCLC have no LNs examined, most of these patients have had sublobar resection. Majority with node-negative disease have fewer than 10 LNs, a large proportion have no mediastinal LNs, raising the possibility of understaging. Patients with pT2Nx do significantly worse than those with pT2N0.