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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and keywords: Occult cancer; CUP; Metastases of unknown primary origin; Unknown primary origin neoplasm; cancers of unknown primary site; neoplasms of unknown primary site

Overview

Historical Perspective

Cancer of unknown primary origin was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
In [year], [gene] mutations were first identified in the pathogenesis of cancer of unknown primary origin.
In [year], the first [discovery] was developed by [scientist] to treat/diagnose cancer of unknown primary origin.

Classification

Cancer of unknown primary origin may be classified according to [classification method] into [number] subtypes/groups:

[group1]
[group2]
[group3]

Other variants of cancer of unknown primary origin include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

Pathophysiology

The pathogenesis of Cancer of unknown primary origin is characterized by [feature1], [feature2], and [feature3].
The [gene name] gene/Mutation in [gene name] has been associated with the development of cancer of unknown primary origin, involving the [molecular pathway] pathway.
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of Cancer of unknown primary origin.
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of Cancer of unknown primary origin.

Causes

Cancer of unknown primary origin may be caused by either [cause1], [cause2], or [cause3].
Cancer of unknown primary origin is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
There are no established causes for cancer of unknown primary origin.

Differentiating Cancer of Unknown Primary Origin from Other Diseases

Cancer of unknown primary origin must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

[Differential dx1]
[Differential dx2]
[Differential dx3]

Epidemiology and Demographics

The prevalence of cancer of unknown primary origin is approximately [number or range] per 100,000 individuals worldwide.
In [year], the incidence of Cancer of unknown primary origin was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

Patients of all age groups may develop cancer of unknown primary origin.

Cancer of unknown primary origin is more commonly observed among patients aged [age range] years old.
Cancer of unknown primary origin is more commonly observed among [elderly patients/young patients/children].

Gender

Cancer of unknown primary origin affects men and women equally.

[Gender 1] are more commonly affected with cancer of unknown primary origin than [gender 2].
The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

There is no racial predilection for cancer of unknown primary origin.

Cancer of unknown primary origin usually affects individuals of the [race 1] race.
[Race 2] individuals are less likely to develop Cancer of unknown primary origin.

Risk Factors

Common risk factors in the development of cancer of unknown primary origin are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

The majority of patients with cancer of unknown primary origin remain asymptomatic for [duration/years].
Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
If left untreated, [#%] of patients with Cancer of unknown primary origin may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
Common complications of Cancer of unknown primary origin include [complication 1], [complication 2], and [complication 3].
Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with Cancer of unknown primary origin is approximately [#%].

Diagnosis

Diagnostic Criteria

The diagnosis of cancer of unknown primary origin is made when at least [number] of the following [number] diagnostic criteria are met:

[criterion 1]
[criterion 2]
[criterion 3]
[criterion 4]

Symptoms

Cancer of unknown primary origin is usually asymptomatic.
Symptoms of cancer of unknown primary origin may include the following:

[symptom 1]
[symptom 2]
[symptom 3]
[symptom 4]
[symptom 5]
[symptom 6]

Physical Examination

Patients with cancer of unknown primary origin usually appear [general appearance].
Physical examination may be remarkable for:

[finding 1]
[finding 2]
[finding 3]
[finding 4]
[finding 5]
[finding 6]

Laboratory Findings

There are no specific laboratory findings associated with cancer of unknown primary origin.

A [positive/negative] [test name] is diagnostic of cancer of unknown primary origin.
An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of Cancer of unknown primary origin.
Other laboratory findings consistent with the diagnosis of Cancer of unknown primary origin include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings

There are no [imaging study] findings associated with cancer of unknown primary origin.

[Imaging study 1] is the imaging modality of choice for cancer of unknown primary origin.
On [imaging study 1], Cancer of unknown primary origin is characterized by [finding 1], [finding 2], and [finding 3].
[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

Cancer of unknown primary origin may also be diagnosed using [diagnostic study name].
Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

There is no treatment for cancer of unknown primary origin; the mainstay of therapy is supportive care.

The mainstay of therapy for cancer of unknown primary origin is [medical therapy 1] and [medical therapy 2].
[Medical therapy 1] acts by [mechanism of action1].
Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Surgery

Surgery is the mainstay of therapy for cancer of unknown primary origin.
[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of Cancer of unknown primary origin.
[Surgical procedure] can only be performed for patients with [disease stage] Cancer of unknown primary origin.

Prevention

There are no primary preventive measures available for cancer of unknown primary origin.

Effective measures for the primary prevention of cancer of unknown primary origin include [measure1], [measure2], and [measure3].

Once diagnosed and successfully treated, patients with Cancer of unknown primary origin are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

References

Solitary Pulmonary Nodule Detected

Step 1: Assess likelihood of cancer
❑ Mayo Clinic Malignancy Risk Calculator

Step 2: Review prior films
Is there a growth?

No previous films
*Refer to step 2A

Yes, growing

No, stable

Step 2A
Enhanced Computed Tomography

Step 2B
Surveillance

Imaging evaluation

Location
❑ Upper lobe
❑ Lower lobe
❑ Middle lobe
Size
❑ < 8mm
❑ > 8mm
Lesion characteristics
❑ Margins (irregular/regular)
❑ Shape (spiculated/rounded)
❑ Attenuation

Other Diagnostic Studies
❑ PET/CT scan

Low risk
❑ < 5%

Intermediate risk
❑ 5-65%

High risk
❑ > 65%

Serial CT scans

Non-surgical biopsy
*Refer to Step 3: Treatment

Surgical resection
*Refer to Step 3: Treatment

Step 3: Treatment

Step 1: Assess likelihood of cancer
❑ Clinical judgment
❑ Mayo Clinic Malignancy Risk Calculator