A Family Secret
Pathlet 006
Daniel Hans '15
with the pathology team

These pathlets are edutainment. This site collects no information about visitors, and cannot substitute for your own doctor's care. There are many questions without clear right-or-wrong answers.

Dietrich, a 45 year old man, presents to you at the insistance of his wife, who gives the history. She complains that for several years he has been getting "the run-around" from physicians who cannot seem to nail down his diagnosis. Initially his symptoms were mild and attributed to "middle age". However, slowly and steadily they have progressed and are now greatly affecting his life.

Deitrich barely moves during the presentation of the chief complaint, and slumps with his head down. His wife says that about three years ago, he began noticing slight memory problems and lack of attention. He breaks in, "Yes, but that's because I don't listen to you because all you do is nag, nag, nag."

The wife resumes, explaining that within the last year both of them noticed balance and equilibrium issues that caused him to feel dizzy. He went to his primary care physician, who sent him to an otolaryngologist. After a quick exam, the otolaryngologist diagnosed benign positional vertigo and performed some inpatient procedures that provided no relief.

The primary care physician then sent him to a psychologist, who diagnosed post-traumatic stress disorder and said the stumbling was symbolic of forgotten life trauma. Three months of "visualization therapy" did not help, and Dietrich refused to continue it.

The primary care physician then prescribed big doses of vitamins. Although his issues with equilibrium were annoying, the patient did not get seriously worried about the state of his health until six months ago, when he began having significant trouble walking, standing, and moving in a coordinated manner.

The patient looks frustrated, inattentive, and does not volunteer anything. The wife carries on about how there must be a cure if you will just look.

Please remember you are a KCUMB alumnus and will practice better medicine.

The High German Doctor

What will you ask?

Diseases in the family?      
Social history?      
Review of Systems?      

Physical exam is remarkable for...

You're glad that you are a KCUMB graduate and don't miss basic findings on physical exam. You are thinking of a cerebellar lesion and wondering about the flame hemorrhage. What's next?

Caloric Testing      
Head Imaging      
Lumbar Puncture      
Nerve conduction velocities      
Routine labs      

Among the following, which do you think is the most likely diagnosis?

Acoustic neuroma
Cerebellar abscess
Metastatic cancer
Pilocytic astrocytoma
Polycythemia vera
Sleep apnea
Syphilitic gumma

If you did not discover the two tumors in the cerebellum on imaging, somebody else did. The resected specimen from the cerebellum is 8.5 grams of tissue composed of cyst wall fragments and other fragments of soft red tissue that measure in aggregate 4.8 x 4.9 x 3.0 cm.


You have no trouble spotting the vessels and the large, pale-staining stromal cells. Under the light microscope, the cells were foamy. A touch preparation showed them to be very positive for lipid ("oil-red O").

You are most interested in distinguishing a HEMANGIOBLASTOMA from a metastatic, well-differentiated RENAL CELL CARCINOMA. This is a famously difficult call on light microscopy.

This will help.... We're going to let you order some immunohistochemistry.

Hemangioblastomas are usually negative for cytokeratin and epithelial membrane antigen (EMA), while renal cell carcinomas usually are positive.

If you are really loaded, aquaporin is usually positive in hemangioblastomas but not renal cell carcinomas, and RCC and CD10 are usually positive in renal cell carcinomas but not hemangioblastomas.
   (stains hemangioblastomas)
   (stains most RCC's, others)
   (stains macrophages, nonspecific)
   (stains epithelium)
Epithelial membrane antigen
   (stains ducts & acini)
Factor VIII
   (stains endothelium)
   (stains glia mostly)
Neuron-specific enolase
   (stains neural, some other)
   (stains most renal cell carcinomas)
   (stains melanoma, some neuro)
   (stains some neural)
   (stains most mesenchymal)

Once you are done, what is your diagnosis?

Well-differentiated renal cell carcinoma


The immunohistochemical stains leave no doubt this is a cerebellar hemangioblastoma.

Dietrich's dad knew he had von Hippel-Lindau disease, because a hemorrhage into his left eye had blinded him. His own father, his sister, and his sister's son all had the disease as well. He told his son but as often happens, it didn't register.

Just because they could, the medical team checked Dietrich for loss of the VHL allele at chromosome 3p25, and the diagnosis of von Hippel-Lindau was confirmed.

He has had no more problems from his genetic syndrome.

Teaching points:

  • Hemangioblastomas are a treacherous call on H&E because the histopathology closely resembles metastatic renal cell carcinoma. Patients with von Hippel-Lindau disease are prone to get either or both. And renal cell carcinoma itself, genetic syndrome or not, is hated for its surprising presentations.
  • Hemangioblastomas cause polycythmia by producing erythropoietin. Whenever anybody has polycythemia, even from being dehydrated, a gunner can say "consider hemangioblastoma."
  • Family history is most important when there's something strange. If you asked, the wife knew the husband's family had members with a disease with a "French" name. Close enough. Eugen von Hippel was a German. Arvid Lindau was a Swede.

"Left Brain, Right Brain"
Painter Unknown

Daniel Hans KCUMB '15

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