Practice question answers upper respiratory tumors

Practice question answers
Upper respiratory tumors
© Jun Wang, MD, PhD

1. A. The microscopic features of fibrotic stroma with irregular dilated vessels are suggestive of nasopharyngeal angiofibroma. Angiosarcoma is characterized by pack vascular proliferation with endothelial atypia. Inverted papilloma is characterized by inward growth of benign squamous epithelium. Nasopharyngeal carcinoma is more common in certain areas, including Middle East. However, it is a type of squamous cell carcinoma that is associated with EBV infection. Olfactory neuroblastoma is characterized by sheets or nests of tumor cells with round to oval nuclei, scant cytoplasm, and expression of keratin and neuroendocrine markers including chromogranin and synaptophysin.

2. A. Nasopharyngeal angiofibroma is positive for androgen receptor. Chromogranin is a neuroendocrine marker that is expressed in neuroendocrine tumors, including carcinoid, small cell carcinoma, and olfactory neuroblastoma. EB virus encoded RNA is an EBV product, and it is positive in nasopharyngeal carcinoma and other EBV associated tumors, such as primary effusion lymphoma, extranodal NK/T cell lymphoma, nasal type, and Burkitt lymphoma. Estrogen receptor is usually positive in certain breast and endometrial cancers. Nuclear protein in testis is positive in NUT midline carcinoma, a type of poorly differentiated squamous cell carcinoma.

3. B. Presence of intercellular bridges is consistent with squamous cell differentiation. Although inverted growth pattern always raises concern of malignancy, lack of invasion makes this lesion more likely to be inverted papilloma. EB virus encoded RNA is an EBV product, and it is positive in nasopharyngeal carcinoma. NUT midline carcinoma, a type of poorly differentiated squamous cell carcinoma with marked atypia, minimal squamous differentiation and positive reactivity to nuclear protein in testis.

4. D. Sinonasal papilloma is associated with HPV. Cigarette smoking is associated with many types of malignancies, including squamous cell carcinoma of larynx, lung, and pulmonary small cell carcinoma. Combined consumption of alcohol and cigarette is associated with squamous cell carcinoma of larynx. EB virus is associated with nasopharyngeal carcinoma. Chromosomal abnormalities (translocation) involving nuclear protein in testis is seen in NUT midline carcinoma, a type of poorly differentiated squamous cell carcinoma.

5. D. Solid nests of cells with round to oval nuclei and scant cytoplasm are suggestive of a broad spectrum of small blue cell tumors, including neuroendocrine tumor and lymphoma. The location, positive reactivity to cytokeratin, S100 and chromogranin with the morphology is more consistent with olfactory neuroblastoma. Nasopharyngeal carcinoma has features of squamous cell carcinoma, and the tumor cells are negative for S100. NUT midline carcinoma is a type of poorly differentiated squamous cell carcinoma with marked atypia. Oncocytic papilloma has cuboidal or columnar cells with eosinophilic granular cytoplasm, lining a fibrous core. It does not present as nests of tumor cells. A patient with history of chronic lymphocytic leukemia/small lymphocytic lymphoma may have localized manifestations, but these tumor cells are positive for at CD45, CD20 and CD23. CD3 is a T cell marker.

6. E. Presence of intercellular bridges is consistent with squamous cell differentiation. Lack of glandular differentiation does not support adenocarcinoma. With the presence of largely variable nuclear morphology, this is most likely a poorly or undifferentiated tumor. With focal presence of squamous differentiation, this is likely a poorly or undifferentiated squamous cell carcinoma. With the location, this is most likely primary poorly differentiated squamous cell carcinoma, such as NUT midline carcinoma, since metastatic tumor to nasal cavity is very rare. Sinonasal papillomas are well differentiated benign tumors. Lymphomas do not have squamous differentiation.

7. C. NUT midline carcinoma is positive for NUT. Mucin production is commonly seen in tumors with glandular differentiation. Androgen receptor is expressed in nasopharyngeal angiofibroma. EBV infection is seen in nasopharyngeal carcinoma.

8. C. Presence of intercellular bridges is consistent with squamous cell differentiation. Marked atypia is usually seen in high grade tumors. With the location, this is most likely a poorly/undifferentiated squamous cell carcinoma, such as nasopharyngeal carcinoma or NUT midline carcinoma. However, negative reactivity to NUT is not compatible with NUT midline carcinoma. Diffuse large B cell lymphoma is positive for CD45. Both Hodgkin lymphoma and diffuse large B cell lymphoma are negative for cytokeratin. Olfactory neuroblastoma does not have squamous differentiation and is positive for S-100.

9. B. EB virus is associated with nasopharyngeal carcinoma. CD20 is a B-cell marker. HHV8 is associated with primary effusion lymphoma and Kaposi sarcoma. S-100 is neuronal and melanocytic marker positive in neuronal and melanocytic tumors, such as olfactory neuroblastoma, neurofibroma, Schwannoma, malignant peripheral nerve sheath tumor and melanoma. Synaptophysin is marker for neuroendocrine differentiation. It is expressed in olfactory neuroblastoma, and neuroendocrine tumors, including small cell carcinoma and carcinoid.

10. B. A small vocal cord lesion composed of fibrous core and squamous lining without atypia is consistent with vocal cord polyp. Recurrent thyroid follicular carcinoma has morphology of follicular differentiation. Chronic lymphocytic leukemia/Small lymphocytic lymphoma usually has sheets of monotonous lymphocytic infiltrate.  Squamous cell carcinoma has atypia. Squamous papilloma has papillary projects, and usually covered by squamous epithelium with certain degree of atypia, including koilocytic changes.

11. E. Vocal cord polyp is associated with chronic irritations including phonotrauma. Alcohol usage in combination of cigarette smoking is associated with laryngeal squamous cell carcinoma. Human papillomavirus is associated with squamous papilloma and squamous cell carcinoma. EB virus is associated with nasopharyngeal carcinoma and some laryngeal squamous cell carcinoma. Vocal cord paralysis may be resulted due to laryngeal recurrent nerve injury associated with either surgery or tumors of surrounding structures including thyroid and esophageal malignancies, but not commonly associated with vocal cord polyps.

12. E. Gross appearance of growth with finger like projections, microscopic features of koilocytic changes with fibrovascular core are most consistent with squamous papilloma. Lack of significant cytological atypia and invasion are not supportive for a malignant process such as squamous cell carcinoma. Angiosarcoma is characterized by pack vascular proliferation with endothelial atypia. Hemangiomas are characterized by pack vascular proliferation without endothelial atypia. Vocal cord polyp is a vocal cord lesion composed of fibrous core and squamous lining without atypia and without finger like projections.

13. D. Human papillomavirus is associated with squamous papilloma and squamous cell carcinoma. EB virus is associated with nasopharyngeal carcinoma and some hypolaryngeal squamous cell carcinoma. Alcohol usage in combination of cigarette smoking is associated with laryngeal squamous cell carcinoma. Phonotraumais associated with vocal cord polyps.

14. C. Presence of intercellular bridges and keratin pearls is consistent with squamous cell differentiation. Nuclear pleomorphism as shown as variation in size, shape and staining pattern is suggestive of malignancy, as in this case, squamous cell carcinoma. Allergic reaction usually has significant eosinophilic infiltrate, but not atypia. Vocal cord polyp is a vocal cord lesion composed of fibrous core and squamous lining without atypia and without finger like projections. Squamous papilloma has papillary projects, and usually covered by squamous epithelium with certain degree of atypia, including koilocytic changes, but not significant pleomorphism and squamous pearls.

15. B. Alcohol usage in combination of cigarette smoking is associated with laryngeal squamous cell carcinoma. Allergic reactions are associated with allergic polyp. EB virus is associated with nasopharyngeal carcinoma and some hypolaryngeal squamous cell carcinoma. Nuclear protein in testis abnormality is seen in NUT midline carcinoma, a type of poorly differentiated squamous cell carcinoma. Phonotraumais associated with vocal cord polyps.

16. A. Location is very important in making diagnosis of congenital neck cysts. Lateral location, squamous lining without atypia is most consistent with a branchial cleft cyst. Malignant lymphoma usually have sheets of lymphocytic infiltration, not scattered lymphocytes, a feature more compatible with chronic inflammatory process. Sebaceous cyst usually are superficially located and contains cream-cheese like keratin debris. Squamous cell carcinoma, regardless of the location, has cytological atypia. Thyroglossal duct cyst is usually located at the anterior midline of neck.

17. E. See discussion in question 16.


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