delving into the occult
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
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Delving into the Occult
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Introduction
Occult • From the Latin
word occultus meaning clandestine, hidden or secret
Occult Cancer• Carcinoma of
unknown primary (CUP)
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Introduction
• Case Study • Diagnostic Work-Up of CUP• Role of Pathology• Future Advances
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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
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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.
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Case Study
Diagnostic Work-up
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Case Study
Clinical Examination• Neck:
Palpable enlarged node in the left neck at Level IV
Firm and mobile Non-fluctuant
• No other significant findings
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Case Study
Biopsy• Fine Needle Aspirate
Cytology• Malignant epithelial
cells with keratinisation and necrosis
• Consistent with metastatic squamous cell carcinoma
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Case Study
Biopsy•Fine Needle Aspirate
Histology•Malignant epithelial cells with keratinisation and necrosis•Consistent with metastatic squamous cell carcinoma
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Case Study
Biopsy•Fine Needle Aspirate
Histology•Malignant epithelial cells with keratinisation and necrosis•Consistent with metastatic squamous cell carcinoma
Where is the primary?
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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
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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
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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
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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
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Case Study
Case Summary• Metastatic SCC• No known primary despite extensive
clinical work-up
CUP
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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
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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
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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
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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?
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Characteristics of CUP
• Early metastases• Absence of symptoms of the primary
tumour• Unpredictable pattern of metastases• Undifferentiated metastases• Aggressive clinical course
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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
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Role of Pathologist
• Determine the histopathological subtype to aid in Locating the primary tumour Optimising treatment options
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Histopathological Subtype
• Carcinoma Adenocarcinoma Squamous Cell
Carcinoma
• Melanoma• Lymphoma• Sarcoma
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Histopathological Subtype
• Carcinoma Adenocarcinoma Squamous Cell
Carcinoma
• Melanoma• Lymphoma• Sarcoma
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Histopathological Subtype
• Carcinoma Adenocarcinoma Squamous Cell
Carcinoma
• Melanoma• Lymphoma• Sarcoma
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Histopathological Subtype
• Carcinoma Adenocarcinoma Squamous Cell
Carcinoma
• Melanoma• Lymphoma• Sarcoma
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Histopathological Subtype
• Carcinoma Adenocarcinoma Squamous Cell
Carcinoma
• Melanoma• Lymphoma• Sarcoma
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Histopathological Subtype
• Carcinoma Adenocarcinoma Squamous Cell
Carcinoma
• Melanoma• Lymphoma• Sarcoma
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Histopathological Subtype
• Carcinoma Adenocarcinoma Squamous Cell
Carcinoma
• Melanoma• Lymphoma• Sarcoma
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Determining Primary Site
Immunohistochemistry
•AE1/3, CAM5.2•S100, MelanA, HMB45•CD45•Vimentin
Tumour Subtype
•Carcinoma•Melanoma•Lymphoma•Sarcoma
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Immunohistochemistry
CK7 / CK20
CK7 + / CK20 +
CK7 + / CK20 -
CK7 - / CK20 +
CK7 - / CK20 -
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Immunohistochemistry
CK7 / CK20
CK7 + / CK20 +
Upper GIT
Pancreas
CK7 + / CK20 -
CK7 - / CK20 +
CK7 - / CK20 -
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Immunohistochemistry
CK7 / CK20
CK7 + / CK20 +
Upper GIT
Pancreas
CK7 + / CK20 -
Thyroid Lung
BreastEndometrium
CK7 - / CK20 +
CK7 - / CK20 -
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Immunohistochemistry
CK7 / CK20
CK7 + / CK20 +
Upper GIT
Pancreas
CK7 + / CK20 -
Thyroid Lung
BreastEndometrium
CK7 - / CK20 +
Colon
CK7 - / CK20 -
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Immunohistochemistry
CK7 / CK20
CK7 + / CK20 +
Upper GIT
Pancreas
CK7 + / CK20 -
Thyroid Lung
BreastEndometrium
CK7 - / CK20 +
Colon
CK7 - / CK20 -
Prostate
KidneyAdrenal
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Adenocarcinoma
Primary Site Immunohistochemistry
Lung TTF-1Pancreas CK19Upper GIT CDX2, CK7Colon CDX2, CK20Liver Hepar-1Thyroid TTF-1Breast ER, GCDFP-15Prostate PSAKidney RCC, PAX8
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Squamous Cell Carcinoma
Primary Site Immunohistochemistry
Lung p63, CK5/6
Head & Neck:
-Oropharyngeal-Nasopharyngeal-Oral (Mouth)
CK5/6
p16 (HPV)EBVp16 and EBV negative
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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%
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Case Study
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Case Study
• Left modified radical neck dissection
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Case Study
Histology• Forty lymph nodes • 2 lymph nodes
positive for metastatic SCC
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Case Study
Histology• Forty lymph nodes • 2 lymph nodes
positive for metastatic SCC
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Case Study
Histology•Forty lymph nodes •2 lymph nodes positive for metastatic SCC•p16 positive
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Case Study
Histology•Forty lymph nodes •2 lymph nodes positive for metastatic SCC•p16 positive
Possible oropharyngeal origin
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Case Study
Staging•N2b
Ipsilateral nodes < 6 cm in greatest dimension
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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.
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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
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Future Model for CUP
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Thank you