Download - Delving into the Occult
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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