The authors conducted a study to analyze and validate the prognostic impact of the novel International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) proposal for an architectural classification of invasive pulmonary adenocarcinomas across all tumor stages. The architectural pattern of a cohort of 500 patients with resected adenocarcinomas (stages I to IV) was retrospectively analyzed in five percent increments and classified according to predominant architecture (lepidic, acinar, solid, papillary, or micropapillary), as proposed by the IASLC/ATS/ERS. Histomorphologic data subsequently were correlated with clinical data, adjuvant therapy, and patient outcome. The authors found that overall survival rates differed significantly between lepidic (78.5 months), acinar (67.3 months), solid (58.1 months), papillary (48.9 months), and micropapillary (44.9 months) predominant adenocarcinomas (P=.007). Lumping patterns into groups resulted in even more pronounced differences in survival rates (pattern group one, 78.5 months; group two, 67.3 months; group three, 57.2 months; P=.001). Comparable differences were observed for overall, disease-specific, and disease-free survival. Pattern and pattern groups were stage- and therapy-independent prognosticators for all three survival parameters. Survival differences according to pattern were influenced by adjuvant chemoradiotherapy; solid-predominant tumors, in particular, had an improved prognosis with adjuvant radiotherapy. The predominant pattern was tightly linked to the risk of developing nodal metastases (P<.001). The authors concluded that besides all recent molecular progress, architectural grading of pulmonary adenocarcinomas according to the IASLC/ATS/ERS scheme is a rapid, straightforward, efficient discriminator for patient prognosis and may support patient stratification for adjuvant chemoradiotherapy. It should be part of an integrated clinical, morphologic, and molecular subtyping to further improve adenocarcinoma treatment.
Warth A, Muley T, Meister M, et al. The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol. 2012;30(13):1438–1446.
Correspondence: Dr. A. M. E. Warth
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Oncotype DX is a reverse-transcriptase polymerase chain reaction-based 21-gene assay validated to provide prognostic and predictive information in the form of a recurrence score for estrogen receptor-positive, lymph node-negative breast cancer. Although the recurrence score was shown to correlate with several histopathological tumor features, a significant proportion of such breast cancer cases showed an apparent discrepancy between recurrence score and risk estimates based on traditional clinicopathological tumor features. The authors conducted a study in which they tested whether a proliferating, cellular stroma or admixed inflammatory cells, or both, may result in an artificially increased recurrence score in low-grade invasive breast cancers. They analyzed the histopathological features in 141 low-grade invasive breast carcinomas, including 41 special type (tubular, cribriform, and mucinous) carcinomas, with an available recurrence score. They evaluated the tumor stroma for increased cellularity and presence of inflammatory cells. Double immunohistochemical stains for pancytokeratin and Ki-67 was performed to assess cell proliferation in tumor versus stromal/inflammatory cells. The clinicopathological features of tumors with a recurrence score of less than 18 (low risk) were compared to those with a recurrence score of 18 or greater (intermediate/high risk). Carcinomas associated with a recurrence score of 18 or more showed lower progesterone receptor immunoreactivity, increased stromal cellularity, and presence of inflammatory cells associated with the tumor. Double immunohistochemical stains showed significantly increased proliferation in stromal/inflammatory cells compared with carcinoma cells in cases associated with a recurrence score of 18 or more. A Ki-67–positive stromal/tumor cells ratio of more than one predicted a recurrence score of 18 or more with an area under the curve of 0.8967 on receiver operator curve analysis (P<.0001). These results suggest that increased stromal cellularity or associated inflammatory cells, or both, in low-grade invasive breast carcinomas may contribute to an increased risk of recurrence according to the Oncotype DX recurrence score. Careful assessment and correlation with histopathological features in such cases may help determine appropriate patient management.
Acs G, Esposito NN, Kiluk J, et al. A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX recurrence scores in low-grade invasive breast carcinomas. Mod Pathol. 2012;25:556–566.
Correspondence: Dr. G. Acs
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The authors conducted a study to evaluate the impact of low estrogen/progesterone receptor (ER/PR) expression and the effect of endocrine therapy on survival outcomes in human epidermal growth factor receptor 2-negative tumors with ER/PR of less than 10 percent, previously labeled as triple negative. In their retrospective review, 1,257 patients were categorized by ER/PR percentages into three groups: ER/PR of less than one percent (group A), ER/PR of one to five percent (group B), and ER/PR of six to 10 percent (group C). A Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models were used to adjust for patient and tumor characteristics. The authors found that groups A, B, and C had 897 (71.4 percent), 241 (19.2 percent), and 119 (9.4 percent) patients, respectively. After a median followup of 40 months, there was no significant difference in three-year recurrence-free survival (64 percent, 67 percent, and 77 percent; P=.34) or overall survival (79 percent, 81 percent, and 88 percent; P=.33) for groups A, B, and C, respectively. ER/PR expression was not an independent predictor for recurrence-free survival (hazard ratio [HR], 1.10; 95 percent confidence interval [CI], 0.86–1.39; P=.46 for group B, and HR, 0.96; 95 percent CI, 0.66–1.38; P=.81 for group C, compared with group A) or overall survival (HR, 1.11; 95 percent CI, 0.84–1.46; P=.46 for group B, and HR, 0.94; 95 percent CI, 0.63–1.42; P=.78 for group C, compared with group A). Endocrine therapy had no impact on survival outcomes (recurrence-free survival, P=.10; overall survival, P=.45) among groups. The authors concluded that in this cohort, an ER/PR level of one to five percent does not appear to have a significant impact on survival outcomes. Survival advantages were seen with an ER/PR level of six to 10 percent. The benefit of endocrine therapy in these patients is unclear.
Raghav KP, Hernandez-Aya LF, Lei X, et al. Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers. Cancer. 2012;118(6):1498–1506.
Correspondence: Dr. Ana M. Gonzalez-Angulo
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The authors conducted a study to quantify the benefit of processing each lymph node in its entirety in colorectal cancer specimens. They examined retrospectively 391 consecutive cases to assess how often cases were upstaged to node positive disease by examining each node in its entirety. The authors found that seven of 391 patients were upstaged by this method. But of those patients, approximately three could have been detected by chance. Therefore, approximately one percent of cases were upstaged correctly. However, six of these seven patients also had at least one additional adverse prognostic factor and would otherwise have been considered high-risk Dukes B cases. The authors concluded that processing all slides of each lymph node significantly increases laboratory workload and is of minimal clinical benefit.
Ervine A, Houghton J, Park R. Should lymph nodes from colorectal cancer resection specimens be processed in their entirety? J Clin Pathol. 2012;65(2):114–116.
Correspondence: Dr. Joe Houghton
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Axillary lymph node status is one of the most powerful prognostic indicators in patients with breast cancer and has implications for adjuvant treatment. It has been demonstrated that enhanced histologic evaluation of axillary lymph nodes, including serial sectioning of paraffin tissue blocks and immunohistochemical (IHC) staining, increases the detection rate for occult metastases. The clinical significance of occult lymph node metastases has been debated. The authors conducted a study in which they identified 267 patients who underwent axillary lymph node dissection between 1987 and 1995 and were lymph node negative according to a routine pathologic evaluation. The evaluation included the complete submission of all lymph nodes and an examination of one hematoxylin and eosin(H&E)–stained section per paraffin block. Patients did not receive systemic chemotherapy or hormone therapy. All of the dissected lymph nodes from these patients were re-evaluated by intensified pathologic methods (serial sectioning with H&E levels plus IHC). Occult metastases were categorized by detection method and size. The clinical significance of the occult metastases was determined. The authors found that 39 patients (15 percent) who had lymph node-negative results on routine evaluation of their axillary lymph node dissection specimens had occult metastases identified. Eight of these patients (20 percent) had macrometastases greater than 2.0 mm, while 15 (40 percent) had micrometastases ranging from over 0.2 mm to 2 mm, and 16 (40 percent) had isolated tumor cells of 0.2 mm or less. The presence of occult metastases and the size of the metastases did not affect recurrence-free or overall survival rates. The authors concluded that the presence of occult metastases did not have clinical significance in this cohort of patients with early stage breast cancer.
Wu Y, Mittendorf EA, Kelten C, et al. Occult axillary lymph node metastases do not have prognostic significance in early stage breast cancer. Cancer. 2012;118(6):1507–1514.
Correspondence: Dr. Aysegul A. Sahin
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Embryonal rhabdomyosarcoma of the uterine cervix is an uncommon presentation of the most common soft-tissue sarcoma in the first decades of life. Unlike embryonal rhabdomyosarcoma in other anatomic sites, in which 70 percent to 80 percent of cases present before nine years of age, the average age in the authors’ series of 14 cervical cases was 12.4 years (median, 13 years), with an age range of nine months to 32 years at diagnosis. Of the 14 cases, 12 presented as a polyp at the cervical os, and two were an infiltrative mass in the cervix without a botryoid polyp. The polyps measured 1.5 cm to 5 cm and all had the histopathological pattern of the sarcoma botryoides variant of embryonal rhabdomyosarcoma, with condensations of primitive and differentiated rhabdomyoblasts beneath the surface epithelium and around endocervical glands. Nodules of benign-appearing cartilage were present in the stroma of six cases (43 percent). One of the embryonal rhabdomyosarcomas from the youngest patient, who was nine months old, also had a distinctive microscopic focus of immature tubular profiles in a primitive stroma. These tubules expressed epithelial and neuroendocrine markers. Two patients had a pleuropulmonary blastoma, one diagnosed nine years before the embryonal rhabdomyosarcoma of the cervix and the other recognized synchronously. This latter nine-year old had a DICER1 germline mutation. One patient presented with hirsutism and had a Sertoli-Leydig cell tumor, an incidentally detected cervical embryonal rhabdomyosarcoma, and nodular hyperplasia of the thyroid. Although a pleuropulmonary blastoma was not documented in the latter patient, ovarian sex-cord stromal tumors and nodular hyperplasia of the thyroid are manifestations of the pleuropulmonary blastoma family tumor and dysplasia syndrome (OMIM 601200). Embryonal rhabdomyosarcoma of the cervix must be distinguished from other rare entities, including adenosarcoma, malignant mixed Mullerian tumor, and low-grade stromal sarcoma, as the former has a better prognosis. Twelve of the 14 patients analyzed by the authors remained disease-free following conservative surgery and chemotherapy. This study suggests that cervical embryonal rhabdomyosarcoma may be another pathological manifestation in the spectrum of extrapulmonary pathology in the setting of pleuropulmonary blastoma.
Dehner LP, Jarzembowski JA, Hill DA. Embryonal rhabdomyosarcoma of the uterine cervix: a report of 14 cases and a discussion of its unusual clinicopathological associations. Mod Pathol. 2012;25:602–614.
Correspondence: Dr. L. P. Dehner
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, assistant professor of pathology and laboratory medicine, University of Kentucky College of Medicine; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.