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Delving into the Occult

Delving into the Occult. Introduction. Occult From the Latin word  occultus  meaning clandestine, hidden or secret Occult Cancer Carcinoma of unknown primary (CUP). Introduction. Case Study Diagnostic Work-Up of CUP Role of Pathology Future Advances. Case Study. Mr X

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Delving into the Occult

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  1. Delving into the Occult

  2. Introduction Occult • From the Latin word occultus meaning clandestine, hidden or secret Occult Cancer • Carcinoma of unknown primary (CUP)

  3. Introduction Case Study Diagnostic Work-Up of CUP Role of Pathology Future Advances

  4. Case Study Mr X Presented to his GP with a 3-week history of left-sided neck swelling Referred to ENT for diagnostic work-up Past History: None of note Non-smoker

  5. Case Study History of Presenting Complaint • Noticed swelling in left neck • no increase in size, non-painful • No other symptoms • no dysphagia, hoarseness, weight loss, fevers, night sweats etc.

  6. Case Study Diagnostic Work-up

  7. Case Study Clinical Examination • Neck: • Palpable enlarged node in the left neck at Level IV • Firm and mobile • Non-fluctuant • No other significant findings

  8. Case Study Biopsy • Fine Needle Aspirate Cytology • Malignant epithelial cells with keratinisation and necrosis • Consistent with metastatic squamous cell carcinoma

  9. Case Study Biopsy Fine Needle Aspirate Histology Malignant epithelial cells with keratinisation and necrosis Consistent with metastatic squamous cell carcinoma

  10. Case Study Where is the primary? Biopsy Fine Needle Aspirate Histology Malignant epithelial cells with keratinisation and necrosis Consistent with metastatic squamous cell carcinoma

  11. Case Study CT Scan of Neck, Thorax, Abdomen & Pelvis 2 lesions in left neck behind sternocleidomastoid muscle, 2cm each Most likely necrotic lymph nodes No other abnormality identified

  12. Case Study Whole Body PET-CT • FDG avid left-sided cervical lymphadenopathy • Small focus of increased FDG uptake at left base of tongue • No other abnormality identified

  13. Case Study Whole Body PET-CT • FDG avid left-sided cervical lymphadenopathy • Small focus of increased FDG uptake at left base of tongue • No other abnormality identified

  14. Case Study Panendoscopy with Left Tonsillectomy & Tongue Biopsies • Panendoscopy revealed no obvious tumour • Left Tonsillectomy: • Reactive lymphoid hyperplasia • Biopsy Left Base of Tongue Biopsy: • No evidence of malignancy

  15. Case Study CUP Case Summary Metastatic SCC No known primary despite extensive clinical work-up

  16. CUP Definition Metastatic tumour detected when the site of the primary origin cannot be identified despite a detailed work-up Accounts for 3 - 5% off all cancers 7th – 8th most frequent malignant tumour 4th most common cause of cancer death

  17. CUP Incidence in Ireland 10 – 13 cases per 100,000 per year Up to 4.7% of all cancer deaths Males > Females Median age at presentation is 65 – 70 years Average survival of 4 – 12 months

  18. CUP with Cervical Nodes • Location of the positive node can indicate the location of the primary tumour • Upper & Middle Neck LN • Head & neck primary • Lower Neck LN • Primary below the clavicles

  19. CUP with Cervical Nodes • Primary tumours tend to be small • 65% less than 1.0 cm • 30% less than 0.5 cm • May be deep in tonsil • Why do we get early nodal metastatic disease from a small primary tumour?

  20. Characteristics of CUP Early metastases Absence of symptoms of the primary tumour Unpredictable pattern of metastases Undifferentiated metastases Aggressive clinical course

  21. Diagnostic Work-Up • History & physical examination • Routine laboratory studies • Serum tumour markers • Chest X-ray • Symptom-directed endoscopy • CT thorax, abdomen & pelvis • Further imaging: PET-CT, Mammogram • Biopsy

  22. Role of Pathologist • Determine the histopathological subtype to aid in • Locating the primary tumour • Optimising treatment options

  23. Histopathological Subtype • Carcinoma • Adenocarcinoma • Squamous Cell Carcinoma • Melanoma • Lymphoma • Sarcoma

  24. Histopathological Subtype • Carcinoma • Adenocarcinoma • Squamous Cell Carcinoma • Melanoma • Lymphoma • Sarcoma

  25. Histopathological Subtype • Carcinoma • Adenocarcinoma • Squamous Cell Carcinoma • Melanoma • Lymphoma • Sarcoma

  26. Histopathological Subtype • Carcinoma • Adenocarcinoma • Squamous Cell Carcinoma • Melanoma • Lymphoma • Sarcoma

  27. Histopathological Subtype • Carcinoma • Adenocarcinoma • Squamous Cell Carcinoma • Melanoma • Lymphoma • Sarcoma

  28. Histopathological Subtype • Carcinoma • Adenocarcinoma • Squamous Cell Carcinoma • Melanoma • Lymphoma • Sarcoma

  29. Histopathological Subtype • Carcinoma • Adenocarcinoma • Squamous Cell Carcinoma • Melanoma • Lymphoma • Sarcoma

  30. Determining Primary Site Immunohistochemistry • AE1/3, CAM5.2 • S100, MelanA, HMB45 • CD45 • Vimentin Tumour Subtype • Carcinoma • Melanoma • Lymphoma • Sarcoma

  31. Immunohistochemistry

  32. Immunohistochemistry

  33. Immunohistochemistry

  34. Immunohistochemistry

  35. Immunohistochemistry

  36. Adenocarcinoma

  37. Squamous Cell Carcinoma

  38. Future Advances Molecular Profiling Gene expression profiling to identify the genetic signature of the CUP Uses RT-PCR and microRNA assays to identify the tissue of origin of the tumour Prediction accuracies of 80 – 90%

  39. Case Study

  40. Left modified radical neck dissection Case Study

  41. Case Study Histology • Forty lymph nodes • 2 lymph nodes positive for metastatic SCC

  42. Case Study Histology • Forty lymph nodes • 2 lymph nodes positive for metastatic SCC

  43. Case Study Histology • Forty lymph nodes • 2 lymph nodes positive for metastatic SCC • p16 positive

  44. Case Study Histology • Forty lymph nodes • 2 lymph nodes positive for metastatic SCC • p16 positive Possible oropharyngeal origin

  45. Case Study Staging • N2b • Ipsilateral nodes < 6 cm in greatest dimension

  46. Conclusion • CUP accounts for 3 – 5% of all cancers and has a poor prognosis. • Diagnostic work-up includes: • Careful clinical history & thorough examination • Routine laboratory tests and tumour markers • Imaging • Biopsy • IHC is an essential part of histopathological assessment in determining the primary site.

  47. Take Home MessagesCUP in Neck Node • Cystic neck node in male > 40 years is metastatic malignancy until proven otherwise • Inadequate/negative aspiration must be followed up with further tissue evaluation • p16 (HPV) positive carcinoma in cervical node may be an oropharyngeal primary • Tonsil and base of tongue are primary suspects • EBV positive carcinoma in cervical node may be a nasopharyngeal primary

  48. Future Model for CUP

  49. Thank you

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