Changes
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==Clinical History==
55 year old male with a right upper lobe lung mass and mediastinal adenopathy.
The patient is a smoker.
==Cytology==
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</gallery>
===Resident Questions===
* <spoiler text="Diagnosis?">Adenocarcinoma. </spoiler>
* <spoiler text="What genetic mutations, if any, are associated with this diagnosis?">
* EGFR testing is performed on these tumors to select patients for tyrosine kinase inhibitor (TKI)therapy (Gefitinib).
* Patients with EML4-ALK fusion, respond to ALK inhibitor (ALKI) (Crizotinib)
** Deletion and inversion on Chromosome 2p
* Patients with KRAS or BRAF mutation do not respond to TKI, ALKI
* KRAS mutations tend to be an adverse prognostic sign
** Seen in mucinous type tumors, smokers and those of non-Asian ancestry
** Most common mutations are in codons 12 and 13 of exon 2
* EGFR
** Point mutation or substitution mutation in the EGFR tyrosine kinase domain
*** Sensitive to EGFR tyrosine kinase inhibitors
**** Exons 19 deletion
**** Exon 21 L858R
**** Exon 18 G719
*** Resistance to EGFR tyrosine kinase inhibitors
**** Exon 20 (insertion V769L, S768I)
**** Exon 19 (D761Y)
</spoiler>
* <spoiler text="Why is it important to distinguish between adenocarcinoma and squamous cell carcinoma?">
* Treatment
** EGFR mutations are found in adenocarcinoma and in some adenosquamous carcinomas
** Bevacizumab is a monoclonal antibody that blocks vascular endothelial growth factor A (VEGF-A), which stimulates angiogenesis in cancer
** Association between fatal hemoptysis in patients with squamous cell carcinoma of the lung treated with Bevacizumab
*** Therefore, Bevacizumab is contraindicated for tumors with squamous cell histology
</spoiler>
==Additional Teaching Points==
===Immunohistochemistry===
* TTF-1 (nuclear stain)
** Thyroid Transcription factor1 regulates transcription of genes specific to the thyroid, lung, and diencephalon
** If metastatic thyroid cancer to the lung is ruled out by morphology or +thyroglobulin; then a +TTF1 supports adenocarcinoma originating from the lung
* P63 (nuclear stain) and 34BE12 (cytoplasmic stain)
** Used for squamous differentiation
* TTF1 is more sensitive than p63
** If a tumor stains for both it is more likely to be adenocarcinoma
* Napsin A(cytoplasmic stain)
** Granular staining pattern
** Marker for adenocarcinoma
{{Cytologically Yours}}
[[Category:Unknowns]]
[[Category:Respiratory]]
55 year old male with a right upper lobe lung mass and mediastinal adenopathy.
The patient is a smoker.
==Cytology==
<gallery heights="250px" widths="250px">
CytologicallyYoursUnknowns201310-1-01.jpg
CytologicallyYoursUnknowns201310-1-02.jpg
CytologicallyYoursUnknowns201310-1-03.jpg
CytologicallyYoursUnknowns201310-1-04.jpg
CytologicallyYoursUnknowns201310-1-05.jpg
CytologicallyYoursUnknowns201310-1-06.jpg
CytologicallyYoursUnknowns201310-1-07.jpg
CytologicallyYoursUnknowns201310-1-08.jpg
</gallery>
===Resident Questions===
* <spoiler text="Diagnosis?">Adenocarcinoma. </spoiler>
* <spoiler text="What genetic mutations, if any, are associated with this diagnosis?">
* EGFR testing is performed on these tumors to select patients for tyrosine kinase inhibitor (TKI)therapy (Gefitinib).
* Patients with EML4-ALK fusion, respond to ALK inhibitor (ALKI) (Crizotinib)
** Deletion and inversion on Chromosome 2p
* Patients with KRAS or BRAF mutation do not respond to TKI, ALKI
* KRAS mutations tend to be an adverse prognostic sign
** Seen in mucinous type tumors, smokers and those of non-Asian ancestry
** Most common mutations are in codons 12 and 13 of exon 2
* EGFR
** Point mutation or substitution mutation in the EGFR tyrosine kinase domain
*** Sensitive to EGFR tyrosine kinase inhibitors
**** Exons 19 deletion
**** Exon 21 L858R
**** Exon 18 G719
*** Resistance to EGFR tyrosine kinase inhibitors
**** Exon 20 (insertion V769L, S768I)
**** Exon 19 (D761Y)
</spoiler>
* <spoiler text="Why is it important to distinguish between adenocarcinoma and squamous cell carcinoma?">
* Treatment
** EGFR mutations are found in adenocarcinoma and in some adenosquamous carcinomas
** Bevacizumab is a monoclonal antibody that blocks vascular endothelial growth factor A (VEGF-A), which stimulates angiogenesis in cancer
** Association between fatal hemoptysis in patients with squamous cell carcinoma of the lung treated with Bevacizumab
*** Therefore, Bevacizumab is contraindicated for tumors with squamous cell histology
</spoiler>
==Additional Teaching Points==
===Immunohistochemistry===
* TTF-1 (nuclear stain)
** Thyroid Transcription factor1 regulates transcription of genes specific to the thyroid, lung, and diencephalon
** If metastatic thyroid cancer to the lung is ruled out by morphology or +thyroglobulin; then a +TTF1 supports adenocarcinoma originating from the lung
* P63 (nuclear stain) and 34BE12 (cytoplasmic stain)
** Used for squamous differentiation
* TTF1 is more sensitive than p63
** If a tumor stains for both it is more likely to be adenocarcinoma
* Napsin A(cytoplasmic stain)
** Granular staining pattern
** Marker for adenocarcinoma
{{Cytologically Yours}}
[[Category:Unknowns]]
[[Category:Respiratory]]