M m it s probably in your head
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M & M “it’s probably in your head”. Kommerien Daling 2-14-08. CASE. 11/19/07: Acute visit. 30 yo WM, C/O tingling Rt leg on 11/14. Resolved while driving to FL for wedding. Next day tingling Lt leg, scrotum, Rt arm, Lt buttock. CHART REVIEW.

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M m it s probably in your head

M & M“it’s probably in your head”

Kommerien Daling 2-14-08


M m it s probably in your head

CASE

  • 11/19/07: Acute visit. 30 yo WM, C/O tingling Rt leg on 11/14. Resolved while driving to FL for wedding. Next day tingling Lt leg, scrotum, Rt arm, Lt buttock.


Chart review

CHART REVIEW

  • 5/05: new patient visit. Depression. Rhinitis. Lexapro. Allegra.

  • 9/05: ED. D/C Lexapro, start Wellbutrin

  • 12/05: CP. Panick attacks. Lexapro.

  • 9/13/06: Anxiety. Mass on testicle. Acute prostatis. Get Gc/chlam. Doxy. Anxiety. Lexapro

  • 9/15/06 Letter to patient: Gc/Chlam neg. RTC if sx continue.

  • 10/16/06: Reschedule. Pt canceled.

  • 5/07: HA. Migraine vs tension.


Chart review1

CHART REVIEW

  • 6/07: 1) Allergic rhinitis 2) Anxiety

    3) Chronic prostatis, controlled.

  • 9/07: stomach pain, N/V. AGE. Viral

  • 10/07: Rt arm pain. Tendinitis.


M m it s probably in your head

CASE

  • 11/19/07: Acute visit.

  • 30 yo WM, H/O anxiety, c/o tingling Rt leg on 11/14. Resolved while driving to FL for wedding. Next day tingling Lt leg, scrotum, Rt arm, Lt buttock.

  • O/ NEU wnl. Rt testis wnl. Lt testis nodule 1 cm

  • A/P 1) Paraesthesias. 2) L test. nodule: epididymal cyst? -> US. 3) Anxiety


Chart review2

CHART REVIEW

  • 9/13/06

    S/ Anxiety. Mass on testicle. Increasing low grade pain after ejaculation.

    O/ Lt testicle w/ mass, prominent epididymis, minimal pain. Some TTP of prostate, but not exquisite. UA-ve.

    A/P 1) Acute prostatitis, Gc/chlam obtained.

    Rx Doxy. 2) Anxiety. Restart Lexapro

    (quit in 3/06).


M m it s probably in your head

CASE

  • 12/12/07 US: area of heterogenous decreased echogenicity with increased Doppler signal in postero-inferior testicle, very suspicious for testicular carcinoma.

    2.1 x 1.4 x 1.5 cm


M m it s probably in your head

CASE

  • 12/13/07 referral CT abd/pelvis, CXR, Referral to Urology, 1/2/08

  • 12/17 Firm mass Lt testicle inferiorly, no hernias. Appointments confirmed with patient. Labs: LDH, AFP, ß-HCG.

    B-12 borderline low -> PO vit B12.


M m it s probably in your head

CASE

  • 1/2/08. Urology note: Pt noticed mass/fullness Lt testicle for 15 months, when initially seen not palpable, was told:

    “it’s probably in your head”

  • Sperm banking & testicular prosthesis discussed with patient

  • 1/10/08 Lt ing radical orchiectomy. Seminoma.


Epidemiology of tc

Epidemiology of TC

  • 2007: New Cases 7920, Deaths 380

  • 1% of all solid tumors in males

  • Most common malignancy in 15-34yo M (25% of cancer cases, 5% of cancer deaths)

  • Peak incidence 25-35yo

  • US life time risk 3-4/1000

  • 3.7/100.000/yr in whites, 0.9/100.000/yr in blacks, 8.2/100.000/yr in Denmark

  • Increasing trends 1960s-80s in whites, 1990s in blacks


Testicular cancer

Testicular cancer


M m it s probably in your head

Risk factors for testis cancer

  • Cryptorchidism (testicularmaldescent)—2–10 fold increase in risk

  • Carcinomain situ (intratubular germ cell neoplasia -> 50% cancer in 5 yrs)

  • H/Otestis cancer or extragonadal germ cell tumour. 2-3%

  • Family history—relativerisk 8–10 fold in brothers, 4-fold in sons of affectedman. (2% absolute risk)

  • HIV infection—increased risk of seminoma (x21?)

  • Caucasian. Danes

  • Testicular trauma

  • Infertility/subfertility 2-3x risk later in life


Risk factors for testis cancer

Risk factors for testis cancer

  • No proven association with:

  • Intra-uterine estrogen/androgen exposure, DES

  • Tight underwear

  • Sedentary lifestyle

  • Early exposure to viruses

  • Vasectomy


M m it s probably in your head

Genetics

Duplication oramplification of the short arm of chromosome 12 (12p)is seenin almost all cases of testis cancer, implying that a key geneis present in this area.


Presentation

Presentation

  • Painless mass

  • Dull ache or heavy sensation in lower abdomen/perianal/scrotum 30-40%

  • Acute pain 10%

  • Gynaecomastia 10%

  • Diffuse swelling/hydrocele

  • Infertility

  • Hematospermia


M m it s probably in your head

Clinical manifestations of testis cancer from metastaticdisease*Systemic symptoms: anorexia, malaise, weight loss * Coughor shortness of breath due to pulmonary metastases * Neck massdue to lymph node metastases * Lower back pain from bulky retroperitonealdisease * Lower extremity swelling due to iliac or caval obstructionorthrombosis (unilateral or bilateral) * Nausea, vomiting orgastrointestinal haemorrhage fromretroduodenal metastases * Bonypain* Central or peripheral nervous system symptoms from cerebral,spinal cord or peripheral nerve root involvement


Testicular mass pain ddx

Testicular mass/pain: DDx

  • Testiculartorsion: acute, severe pain is a common presenting feature

  • Epididymitis/epididymo-orchitis:associated with fever, pain not as acute

  • Testicular cancer

  • Hydrocoele

  • Varicocoele

  • Hernia

  • Hematoma, trauma

  • Spermatocele

  • Vasculitis: Polyarteritis nodosa, HSP

  • Acute idiopathic scrotal edema

  • Syphilitic gumma


Testis cancer evaluation

Testis Cancer ? Evaluation

  • PE: abd, scrotal exam(testis, epididymis, cord, skin), inguinal region, breasts, rectal, supra clavicular lymphnodes

  • UA

  • Scrotal US, color Doppler


Chronic testicular pain

Chronic testicular pain


Acute scrotal pain

Acute scrotal pain


Scrotal us findings

Scrotal US findings

  • Sufficient for dx of TC in majority

  • Conditions which may mimic neoplasia: inflammation, hematoma, infarct, fibrosis, tubular ectasia

  • Small superficial calc. -> no futher eval

  • Microcalcifications: possible CIS

  • MRI if US inconclusive, NPV 100%, PPV 71%


Evaluation for staging

Evaluation for staging

  • Tumor markers AFP, HCG, LDH

  • CXR, CT abd/pelvis, CT or MRI brain PRN


Testicular cancer1

Testicular cancer

  • 95% GCT, 5% others (Leydig, lymphoma)

  • Sx prior to Dx 17-87 wks

  • Tumor doubling 10-30 days


M m it s probably in your head

LDH: elevated in 50%, not specific to type, proportionate to tumor size


Staging of tc

Staging of TC

  • Stage I - Stage I testicular cancer is limited to the testis/epididymis/scrotum/spermatic cord.

  • Stage II - Stage II testicular cancer involves the testis and the retroperitoneal or para-aortic lymph nodes usually in the region of the kidney.

  • Stage III - Stage III implies spread beyond the retroperitoneal nodes based on physical examination, x-rays, and/or blood tests. Stage III is subdivided into nonbulky stage III versus bulky stage III.


M m it s probably in your head

  • Primary tumor (T) - The extent of primary tumor is classified after radical orchiectomy.

  • pTX: Primary tumor cannot be assessed (if no radical orchiectomy has been performed, TX is used.)

  • pT0: No evidence of primary tumor (e.g., histologic scar in testis)

  • pTis: Intratubular germ cell neoplasia (carcinoma in situ)

  • pT1: Tumor limited to testis and epididymis without lymphatic/vascular invasion

  • pT2: Tumor limited to testis and epididymis with vascular/lymphatic invasion, or tumor extending through the tunica albuginea with involvement of the tunica vaginalis

  • pT3: Tumor invades the spermatic cord with or without vascular/lymphatic invasion

  • pT4: Tumor invades the scrotum with or without vascular/lymphatic invasion


M m it s probably in your head

  • Regional lymph nodes (N)

  • NX: Regional lymph nodes cannot be assessed

  • N0: No regional lymph node metastasis

  • N1: Metastasis in a single lymph node, 2 cm or less in greatest dimension

  • N2: Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension

  • N3: Metastasis in a lymph node more than 5 cm in greatest dimension


M m it s probably in your head

  • Distant metastasis (M)

  • MX: Presence of distant metastasis cannot be assessed

  • M0: No distant metastasis

  • M1: Distant metastasis

  • M1a: Non-regional nodal or pulmonary metastasis

  • M1b: Distant metastasis other than to non-regional nodes and lungs


M m it s probably in your head

  • Serum tumor markers (S)

  • SX: Tumor marker studies not available or not performed

  • S0: Tumor marker levels within normal limits

  • S1: LDH < 1.5 X Normal and HCG (mIu/ml) < 5000 and AFP (ug/ml) < 1000

  • S2: LDH 1.5-10 X Normal or HCG (mIu/ml) 5000-50,000 or AFP (ug/ml) 1000-10,000

  • S3: LDH > 10 X Normal or HCG (mIu/ml) > 50,000 or AFP (ug/ml) > 10,000


M m it s probably in your head

Stage 0

pTis, N0, M0, S0

Stage I

pT1-4, N0, M0, SX

Stage IA

pT1, N0, M0, S0

Stage IB

pT2, N0, M0, S0pT3, N0, M0, S0pT4, N0, M0, S0

Stage IS

Any pT/Tx, N0, M0, S1-3

Stage II

Any pT/Tx, N1-3, M0, SX

Stage IIA

Any pT/Tx, N1, M0, S0Any pT/Tx, N1, M0, S1

Stage IIB

Any pT/Tx, N2, M0, S0Any pT/Tx, N2, M0, S1

Stage IIC

Any pT/Tx, N3, M0, S0Any pT/Tx, N3, M0, S1

Stage III

Any pT/Tx, Any N, M1, SX

Stage IIIA

Any pT/Tx, Any N, M1a, S0Any pT/Tx, Any N, M1a, S1

Stage IIIB

Any pT/Tx, N1-3, M0, S2Any pT/Tx, Any N, M1a, S2

Stage IIIC

Any pT/Tx, N1-3, M0, S3Any pT/Tx, Any N, M1a, S3Any pT/Tx, Any N, M1b, Any S


Prognosis

Prognosis

  • 1963 5-yr survival 63%

  • Current 5yr survival > 95%

  • Stage 1 98%

  • Stage 2 early: > 90%

  • Stage 2 late: similar to stage 3

  • Stage 3: 90/75/50%


Treatment stage 1

Treatment stage 1

  • Seminomas : surveillance,

    radiation,chemotherapy

  • Nonseminomas: surveillance, retroperitoneal lymphnode resection, chemotherapy

    70-80% cured with orchiectomy alone.

    disease-specific survival in the range of 98%

    to100% regardless of which approach


Treatment stage 2

Treatment stage 2

  • small-volumeretroperitoneal metastases and tumormarker levels wnl:

    RPLND for NS

    RXT for seminoma

  • larger-volume diseaseor elevated serum tumor markers or both: chemotherapy


Treatment stage 3

Treatment stage 3

  • good-risk tumors:

    9 wk BEP or 12wk EP

  • intermediate-risk and poor-risk tumors:

    12 wk BEP.

  • Relapseafter first-line chemo can be cured 2n-line therapy 25% to 45% of the time


Early side effects

Early side effects

Chemo

  • pancytopenia, fatigue, nausea, vomiting, hearingloss, peripheral neuropathy, and reducedrenal function,loss of work time

    Radiation

  • Nausea, fatigue, loss of work


Long term side effects of adjuvant treatment

Long term side effects of adjuvant treatment

  • In/subfertility, hypogonadism

  • 2ndary tumors

  • Increased cardiovascular events

  • Increased risk of metabolic syndrome

  • Pulmonary fibrosis

  • Pulmonary death in 0.2% - 2% (4 cycles)

  • Death from infectious diseases

  • peripheral neuropathy, hearing loss,

  • tinnitus, Raynaud phenomenon

  • Renal insufficiency


Testicular cancer follow up

Testicular Cancer. Follow Up

  • Frequency, duration & testing depends on stage, type, and treatment


M m it s probably in your head

Clinical Stage I Seminoma - Treated with Adjuvant Radiation(Nichols Protocol)

  • Year 1: Tumor Markers and Chest X-ray done

    every 2 months

  • Year 2: Tumor Markers and Chest X-ray done

    every 4 months

  • Years 3-5: Tumor Markers and Chest X-ray done

    every 6 months

  • After Year 5: Tumor Markers and Chest X-ray done

    once a year


M m it s probably in your head

Clinical Stage I Seminoma - Treated with Surveillance only (Nichols Protocol)

  • Year 1: Tumor Markers and Chest X-ray done

    every 2 monthsAbdominal CT scan done every 3 months

  • Year 2: Tumor Markers and Chest X-ray done

    every 2 monthsAbdominal CT scan done every 4 months

  • Years 3-5: Tumor Markers and Chest X-ray done

    every 6 monthsAbdominal CT scan done every 6 months

  • After Year 5: Tumor Markers and Chest X-ray done once a year


Cis intra tubular gct

CIS (intra tubular GCT)

Suspect and consider biopsy in:

  • Contralateral testis of TC patient

  • Intersex patients (Klinefelter)

  • Selected cases with in/subfertility: atrophic testis & microcalcifications on US

  • Assumed extra gonadal GCT


M m it s probably in your head

CIS

  • Dx: surgical biopsy 3x3 mm, 30-40 tubules is representative

  • Eval: staging with CXR, CT, markers

  • Treatment

    Unilateral: orchiectomy

    Bilateral or contralateral: local RXT & F/U bx.

  • Consider semen cryopreservation

  • Check testosteron levels, replacement PRN


Screening

Screening

The USPSTF recommends against routine screening for testicular cancer in asymptomatic adolescent and adult males.

No evidence that screening with clinical examination or testicular self-examination is effective in reducing mortality from testicular cancer. Even in the absence of screening, the current treatment interventions provide very favorable health outcomes. Given the low prevalence of testicular cancer, limited accuracy of screening tests, and no evidence for the incremental benefits of screening, the USPSTF concluded that the harms of screening exceed any potential benefits.

  • USPSTF recommendation: D


Nci pdq physician data query

NCI / PDQ (physician data query)

  • Benefits Based on fair evidence, screening for testicular cancer would not result in an appreciable decrease in mortality, in part because therapy at each stage is so effective.

  • Harms Based on fair evidence, screening for testicular cancer would result in unnecessary diagnostic procedures with attendant morbidity.

  • Direction and Magnitude of Effect: Fair evidence of no reduction in mortality; good evidence for rare but serious harms.


M m it s probably in your head

Drawing 1. Cup your scrotum with one hand to see if it feels normal.

Drawing 2. Feel for any lumps in or on the side of the testicle.

Drawing 3. Feel along the epididymis for swelling.


Returning to case

Returning to CASE

  • Stage 1 seminoma

  • Uncomplicated recovery from surgery

  • Uro referred to radio-onc

  • Has chosen for adjuvant RTX

  • Patient still to decide on sperm banking

  • Operation report and pathology report do not mention biopsy of the contra-lateral testicle


Factors leading to delayed dx

Factors leading to delayed Dx

  • “Atypical” presentation with pain

  • No US obtained at first presentation

  • Patient canceled F/U appointment

  • Subsequently no continuity of care

  • Difficult-to-read office notes

  • Prior diagnosis of anxiety ?

  • Embarrasment w/regard to scrotal exam ?


Recommendations for practice

Recommendations for practice

  • Low-to-no threshold for scrotal US

  • Recognize atypical presentations

  • Continuity of care

  • Legible hand writing: notes and signature

  • Contactibility of physician and patient

  • Be aware of embarrasment


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