Cancer of Unknown Primary

Over at The Lands, we discussed cancers without a known primary source. Our own Dr. Dowell, program director of the Hematology/Oncology fellowship program wrote an excellent review of the topic – take a look at the summary below:

  • Clinical presentation: cancers of unknown primary site account for approximately 5% of cancers; patients typically present with symptoms that originate from metastatic lesions.
  • Diagnosis:
    • History, physical, abdominal CT, PET, serum PSA, mammography, and  symptom-directed radiologic or endoscopic evaluation.
    • Tumor markers are not useful diagnostically!
    • Tissue is the issue! Must get a biopsy from the most accessible site. Typically, the histology reveals adenocarcinoma (60%), poorly differentiated (35%), and squamous cell carcinoma (5%).
      • Adenocarcinoma: Primary site identified in only 15-20% of patients. Pancreas, liver/gallbladder, and lung account for 40-50%. Breast and prostate are rare. Immunohistochemistry can be used to diagnose prostate cancer (PSA stain) and thyroid cancer (thyroglobulin stain).
      • Poorly differentiated cancers:  immunoperoxidase staining can help to diagnose specific tumors like lymphoma, carcinomas (prostate, thyroid, neuroendocrine, germ-cell tumors), melanoma, and sarcoma.
      • Squamous cell cancers: if there is cervical lymph node involvement, primary tumor in head and neck should be sought with panendoscopy
  • Treatment: often, the disease severity or symptoms will require empiric therapy based on general area of the body that is involved:
    • Female with peritoneal mets: treat for epithelial ovarian cancer
    • Female with axillary lymph node mets: treat for breast cancer
    • Male with elevated PSA: treat for prostate cancer with hormonal therapy (androgen deprivation)
    • Cervical LAD: treat for locally advanced SCC of head and neck
    • Lower cervical or supraclavicular LAD: consider primary lung cancer and poor prognosis
    • Inguinal node LAD: primary site almost always identified (genital or anorectal) – treat accordingly
  • For more information on effective chemotherapy, check out


“Sick guy, sick guy.” You will hear those words of wisdom from Dr. Girod with every asthmatic patient – and he is right. Asthma can be difficult to manage in emergent situations due to the severity of bronchospasm, the rapidity of their decline, and the often subtle changes that indicate impending respiratory failure (i.e. a normal PCO2). However, we can avoid such dire situations through evidence-based outpatient care. Take a look at the following approach to the management of asthma: 



Am Fam Physician. 2010 Nov 15;82(10):1242-51.


Ask the Expert: HIV Treatment and Pregnancy

Continuing the series of “Ask the Expert”, Dr. James Cutrell, Assistant Professor in the Department of Medicine Infectious Disease Division, comments on treatment of HIV patients who are pregnant. A topic that is definitely high-yield in preparation for internal medicine boards. Below are Dr. Cutrell’s comments:

“Here is a link to the most recent guidelines on HIV and pregnancy published in March of this year.  This is the summary of the major changes with links to the full guidelines and different sections.

The following are the key take home points for the residents:

  • All HIV-infected women should be virally suppressed on ART if contemplating pregnancy.
  • All HIV-infected women, either known or newly diagnosed, should be started on ART regardless of CD4 count to achieve maximal viral suppression prior to delivery and to reduce perinatal transmission of HIV.
  • IV zidovudine (AZT) is only administered intrapartum to mothers with a detectable VL > 1,000 copies/mL at time of delivery or if rapid HIV Ab screen is positive and confirmatory testing is pending.
  • Due to increased experience and longitudinal safety data, several additional ART drugs have been added to the preferred regimens in pregnancy in addition to the traditional combination of zidovudine-lamivudine and lopinavir-ritonavir.
    • NRTI: Tenofovir plus emtricitabine or Abacavir plus lamivudine
    • PI: Ritonavir-boosted atazanavir
    • NNRTI: Efavirenz only after first 8 weeks of pregnancy
  • Historically, efavirenz use has been discouraged in women of child-bearing age due to potential teratogenicity.  Although current data does not suggest a significant increase in birth defects, an increase in neural tube defects from 1st trimester exposure could not be completely excluded due to small numbers.   The US Guidelines state that women of childbearing age should have a pregnancy test and be counseled to use contraception and avoid pregnancy prior to starting efavirenz based regimens.  Women who are pursuing pregnancy should be treated with alternative regimens if possible.  However, the period of risk for the fetus is only in the first 6-8 weeks (1st trimester) which usually has past before a pregnancy is recognized; therefore, a woman who is beyond the 8 week period can be started on an efavirenz-based regimen if ART-naïve or can continue it if she is already on efavirenz and virologically suppressed and has become pregnant.
  • The UK and WHO guidelines do not recommend restrictions on the use of efavirenz in pregnancy or women desiring to have children.

Choosing Wisely

Dr. Solow, Dr. Kazi, and Dr. Makris recently published the 2014 Update in Rheumatology in the Annals of Internal Medicine. In it, they highlight the Choosing Wisely Campaign and the Top 5 Tests Rheumatologists Should Question:

1. Do not test antinuclear antibody subserologies without a positive antinuclear antibody titer and clinical suspicion of immune-mediated disease (Grade 1C).

2. Do not test for Lyme disease as a cause of musculoskeletal symptoms without an exposure history and appropriate examination findings (Grade 1A).

3. Do not perform magnetic resonance imaging of the peripheral joints to routinely monitor inflammatory arthritis (Grade 1B).

4. Do not prescribe biologic agents for RA before a trial of methotrexate (or other conventional nonbiologic DMARD) (Grade 1A).

5. Do not routinely repeat dual-energy x-ray absorptiometry scans more often than once every 2 years (Grade 1C).

Immunization of the Immunocompromised

We all know the standard dictum: no live vaccines for patients with a compromised immune system. Sounds easy enough! In the clinic, however, it can be difficult to discern to which patients this dogma should apply. At the point of care, it can be even more difficult to remember which vaccines are live, as opposed to inactivated. Take a look at some of the important secondary immunodeficiencies and the live virus vaccines that should be avoided in this population.

  • SELECTED SECONDARY IMMUNODEFICIENCIES (adapted from Mahon et al. The Immunocompromised Patient. Can Fam Physician 1987; 33:349-359).

    • Drugs: corticosteroids (≥ prednisone 20 mg/day equivalent for 2 weeks or more, and within 3 months of stopping), azathioprine, cytotoxic agents, TNF-inhibitors, radiotherapy
    • Diabetes Mellitus
    • Infection: AIDS, influenza, miliary TB
    • Alcoholism
    • Chronic renal failure
    • Hematological disease (i.e. neutropenia, lymphomas, leukemias, multiple myeloma)
    • Splenectomy
    • Severe protein-calorie malnutrition
    • Protein-losing states (nephrotic syndrome, thermal burns, protein-losing enteropathies)

Take a look at the full IDSA vaccination guidelines here.

Utility of MRI in Evaluating Inflammatory Myopathies

Today at VA Morning Report we talked about the utility of MRI in evaluating a patient with suspected inflammatory myopathy. MRI with STIR can accurately detect the extent and intensity of muscle inflammation. STIR stands for Short TI Inversion Recovery, as it suppresses signaling from fat on MRI. The advantage of MRI is that it can assess large areas of muscle which can reduce sampling error. However, it is not specific to a particular disease and can’t distinguish rhabdomyolysis, muscular dystrophy, or metabolic myopathy.

Image below is MRI with STIR of proximal lower extremities. White arrows show symmetrical hyperintensity in the muscles of the proximal lower extremities due to juvenile dermatomyositis. 


(Credit Image: Indiana University School of Medicine Department of Radiology)

Check out this short review of MRI findings in myopathies:

MRI Findings in Inflammatory Muscle Diseases and Their Noninflammatory Mimics

Ask the expert: What do you mean I can’t eat meat!?!?

Continuing our series of posts, “Ask the Expert”, Dr. Dave Khan, Professor of Internal Medicine in the Division of Allergy and Immunology at UT Southwestern, summarizes the findings of a recently discovered allergy to certain meats. 

Delayed meat anaphylaxis: A New Type of Food Allergy

“Within the last 7 years, an identification of a new type of food allergy has been discovered. The story begins with the realization that patients treated with the monoclonal antibody cetuximab, developed anaphylaxis with the first infusion. The majority of these reports were localized to the Southeast United States. A detailed investigation of the serum led to the identification of preexisting IgE antibodies to the oligosaccharide galactose-a-1,3 galactose (alpha-gal). Identification of IgE to alpha-gal led to the realization that IgE was associated with a novel form of food allergy. These patients reported urticaria or anaphylaxis starting 3-6 hours after eating beef, pork, or lamb. While cases of alpha-gal IgE have been reported in Europe and Australia, in the U.S., most cases have occurred in the Southeast. Scott Commins from the Univ. of Virginia has investigated this phenomenon and has identified that bites from the lone star tick are associated and likely causal of the alpha-gal IgE response. Recent reports from Commins’ group has confirmed the delayed nature of the reactions and basophil activation studies indicate that the relevant antigen does not enter the bloodstream until 3-5 hours after consumption of red meat, resulting in the delayed appearance of the allergic reaction. While less common in Texas (I have only seen one case), the discovery of this form of delayed food anaphylaxis has certainly reshaped how we evaluate patients with anaphylaxis.”

Thanks to Dr. Khan for contributing to the post! 


Lone Star Tick

Credit: CDC Public Image Library

UTSW Internal Medicine

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