Ki-67 Immunoreactivity in the Differential Diagnosis of Pulmonary Neuroendocrine Neoplasms in Specimens With Extensive Crush Artifact

Aslan, Deniz; Gulbahce, H. Evin; Pambuccian, Stefan E.; Jessurun, José

doi:10.1309/qyv0-5vge-gkul-2rtt

Cited by 43 publications

(40 citation statements)

References 27 publications

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“…The Ki-67 proliferative index has recently been considered to be useful in distinguishing between the various subtypes of NE tumors, particularly in small biopsy and cytology specimens. The Ki-67 proliferation rate of TC is less than 2% and AC is less than 20% (typical rate ~10%), while the two high-grade NE tumors are higher than 20% (typical rate for SCLC is 60-100%) (6,9,10). The Ki-67 index of this case was 25%.…”

Section: Case Reportmentioning

confidence: 66%

Small-cell lung carcinoma with long-term survival: A case report

et al. 2011

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Abstract. Small-cell lung carcinoma is the most aggressive among lung cancer subtypes, has a poor prognosis and is highly associated with smoking. We present a case of small-cell lung carcinoma in a patient who had never smoked and has survived for 14 years without achieving a complete remission since the first relapse. His long-term survival may be ascribed to the slow growth of the cancer cells, limited metastasis and favorable responses to the treatments he has received. During these 14 years, only two lymph node metastases and a single metastasis to the brain developed. His small-cell lung carcinoma has been well controlled each time by the various treatments he has received, including chemotherapy, radiotherapy and surgery. Pathologically, the tumor was a typical small-cell lung carcinoma with extensive necrosis. Results showed the mitotic rate and the cell proliferation markers to be greater than those in the intermediate-grade atypical carcinoid, but relatively low. Thus, we conclude that this case belongs to an overlap between intermediate-and high-grade neuroendocrine tumors. IntroductionThe 2004 World Health Organization (WHO) classification proposed four subtypes of pulmonary neuroendocrine (NE) tumors: low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC) and two high-grade tumors, large cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC) (1). SCLC is a highly aggressive cancer and results in mortality in 2-4 months without treatment. Most patients respond to primary therapy, but survival remains poor and median survival times are reported to be approximately 24 months in limited disease and 12 months in extensive disease (2,3). In this study, we present a case of SCLC in a never smoker who has survived for 14 years without achieving a complete remission following the initial relapse. Case reportIn November 1996, a 44-year-old male, with no history of smoking, presented at the Osaka Medical Center for Cancer and Cardiovascular Diseases with an abnormal hilar shadow in the left lung, complaining of cough and dyspnea. A computerized tomography (CT) scan revealed a 4.5x3.0 cm hilar mass in the left lung (Fig. 1A). The patient was cytologically diagnosed with SCLC by bronchoscopic examination (Fig. 1B). Metastatic workup demonstrated that he had limited disease, cT2aN2M0 stage IIIA (the 7th edition of the TNM system for lung cancer). The values of serum neuron-specific enolase and carcinoembryonic antigen were within normal limits and the pro-gastrin-releasing-peptide (ProGRP) was not measured at the time. The patient received four cycles of chemotherapy consisting of cisplatin (CDDP) and etoposide, with concurrent thoracic radiation of 44 Gy at 2.2 Gy/fraction daily. The treatment resulted in a complete response. Prophylactic cranial irradiation was not performed since there was no evidence to recommend it at the time (4).The patient remained asymptomatic and no sign of disease recurrence was detected until December 1998, when right mandibular lymphadenopath...

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Section: Case Reportmentioning

confidence: 66%

Small-cell lung carcinoma with long-term survival: A case report

et al. 2011

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“…The difficulties in classifying these tumours arise in rare tumours that show mitotic activity just slightly or focally exceeding 2/2mm 2 or 10/2mm 2 which otherwise would qualify as AC or LCNEC respectively (4). Also, in small biopsies with extensive crush artifact it is difficult to count mitotic figures and when the amount of tumour tissue is limited (5,6). To overcome these difficulties, an effective grading system for digestive NETs was recently introduced by the European Neuroendocrine Tumour Society and endorsed by the WHO and the American Joint Cancer Committee (7).…”

Section: Clinico-pathological Parametersmentioning

confidence: 99%

Proliferation marker (ki67) in sub-categorization of neuroendocrine tumours of the lung

Garg¹,

Bal²,

Das³

et al. 2018

TJPATH

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Objective: The 2015 WHO classification classifies neuroendocrine tumours (NET) of the lung into typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma based on morphology alone. Mitosis is the major parameter for this classification, and thus several studies have focused on the role of Ki67 in these tumours but without conclusive results. The aim of the study was to categorize neuroendocrine tumours of the lung based on morphology and to assess the utility of Ki67 in diagnosis. Material and Method:The study included 42 cases (23 biopsies and 19 lobectomy specimens) of neuroendocrine tumours (excluding small cell carcinoma). Haematoxylin & eosin stained sections, immunohistochemistry for neuroendocrine markers and Ki67 were studied.Results: Based on WHO criteria, cases were classified as typical carcinoids (83.3%), atypical carcinoids (12%) and large cell neuroendocrine carcinomas (4.7%). The Ki67 index ranged between 1%-10% (mean 2.6%), 10%-30% (mean 19%), 35%-50% (mean 42.5%) in typical carcinoid, atypical carcinoid and large cell neuroendocrine carcinoma respectively. Using the ROC curve, the cut off value of Ki67 for typical and atypical carcinoids was 7.5% (P value<0.001), and for atypical carcinoid/large cell neuroendocrine carcinoma was 32.5% (P value=0.051). On comparing the size and infiltration pattern (both local and lymphovascular invasion) of tumours in resected specimens, there was no association with the proliferation index (P value >0.05). Conclusion:Morphological features are the gold standard for subtyping of neuroendocrine tumours. Ki-67 is a potentially meaningful marker for sub-categorization of lung NETs, especially in small biopsies. However, the size and infiltrative pattern of the tumours are independent of the proliferation index.

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“…While the mitotic count is an important component of the classification of pulmonary neuroendocrine tumors, it can be difficult to assess in limited biopsies. Mitoses can be difficult to distinguish from apoptotic cells and may be obscured by crush artefact (4,(44)(45)(46). Also, evaluating mitotic count is time consuming and is subject to interobserver variability (37).…”

Section: Ki-67 In Pulmonary Neuroendocrine Tumorsmentioning

confidence: 99%

“…Studies performed using the current classification of pulmonary neuroendocrine tumors have shown an association between the Ki-67 PI and the grade of the neuroendocrine carcinoma (41,45,(47)(48)(49)(50)(51)(52)(53)(54)(55)(56). Although recent studies have attempted to identify the cutoff points for the Ki-67 proliferative indices for each diagnostic category of pulmonary neuroendocrine tumor (41,48,56), a consensus on how the Ki-67 proliferative index should be integrated into the diagnostic algorithm has not been established in detail (34,57).…”

Section: Ki-67 In Pulmonary Neuroendocrine Tumorsmentioning

confidence: 99%

Ki-67 expression in pulmonary tumors

Chirieac

2016

Transl. Lung Cancer Res.

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Ki-67 Immunoreactivity in the Differential Diagnosis of Pulmonary Neuroendocrine Neoplasms in Specimens With Extensive Crush Artifact

Cited by 43 publications

References 27 publications

Small-cell lung carcinoma with long-term survival: A case report

Small-cell lung carcinoma with long-term survival: A case report

Proliferation marker (ki67) in sub-categorization of neuroendocrine tumours of the lung

Ki-67 expression in pulmonary tumors

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