Pathlet 008
Sanam Vakassi '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.

Ruth Sievers
"Young Man"
A teenaged boy complains of a lump in his forearm. It has been there for three weeks and is growing rapidly. He also complains that he is having trouble urinating or having bowel movements, and reports of seeing blood in his urine. The boy's mother also noticed that in the past couple of weeks he was having a lot of nose bleeds. The mother began to worry about him and decides to take him to your office.

On questioning, the patient reports of having considerable pain over the past few weeks in the region of his left eye. He thought this was a headache, and was taking acetaminophen to try to control the pain. He was also experiencing general symptoms of weakness, fatigue, fever, and loss of appetite.

Past medical history is remarkable for known Neurofibromatosis Type 1, diagnosed by a geneticist who saw him because his father also has the disease. His past surgical history includes a fracture from a bicycle accident. He is not taking any prescribed medications. The teenage boy also takes Flinstone vitamins once every morning.

He does not smoke, he does not drink alcohol, and he does not use recreational drugs.

Physical exam reveals that the left eye protrudes slightly forward. ("Gosh. I did not notice that.") There is a 4 cm soft slightly tender mass on the centar of the palmar aspect of the left forearm. There are several large freckles in each armpit, and several soft slightly elevated nodules on the face and trunk, none greater than 6 mm. He has normal heart and bowel sounds. Temperature is 99.9 F, pulse 58, respiratory rate 11, blood pressure 120/80. No other pertinent physical findings.

This is a real patient, by the way. All of the follow entities are worth considering. Which ones do you think are most likely?

Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Ewing Sarcoma / Primitive Neuroectodermal Tumors
Gorlin Syndrome
Li-Fraumeni Syndrome
Nevoid Basal Cell Carcinoma Syndrome
Non-Hodgkin Lymphoma
Rubinstein-Taybi Syndrome
Wilms Tumor

These are all good ideas. The patient's history of neurofibromatosis and the physical signs supporting is raise his risk for pheochromocytoma and neurofibromas. In any youngster with bumps, it's good to think of nevoid basal cell carcinoma syndrome since the consequences of missing this are so serious. At Junior's age, Wilms tumor, neuroblastoma, and acute lymphoblastic leukemia are still considerations. Acute myelogenous leukemia sometimes presents as a chloroma behind the eye. A retro-orbital mass with new tumors elsewhere in a young person would make any physician think of a rhabdomyosarcoma.

Labs show no abnormalities. Scans confirm a left retro-orbital mass on the left side. There is also a 10 cm homogeneous mass on the left side of the pelvis impinging on the bladder outlet and rectum. The kidneys and adrenals are free of masses.

A core biopsy of the mass on the forearm is obtained for diagnosis.


Which are considerations now?

Acute lymphoblastic leukemia
Acute myelogenous leukemia
Alveolar rhabdomyosarcoma
Ewing sarcoma
Malignant lymphoma
Small cell / oat cell carcinoma

This is a "tumor of small blue cells." The arrangement of the cells would make a pathologist looking at the slide "cold" think of an alveolar rhabdomyosarcoma, but the fibrovascular septa aren't as well-developed as most. In any case, we're going to need some immunohistochemistry.
   (most ALL)
   (almost all leukocytes)
   (most Ewing)
   (skeletal muscle)
Muscle-specific actin
   (skeletal muscle)
   (myelogenous leukemia)
   (skeletal muscle)
   (skeletal muscle)
   (skeletal muscle)
Neuron-specific enolase
   (almost all leukocytes)
   (neuroblastoma, others)
   (sarcomas, more)
   (Wilms marker)

Once you are done, what is your diagnosis?

Acute lymphoblastic leukemia
Acute myelogenous leukemia
Alveolar rhabdomyosarcoma
Ewing sarcoma
Malignant lymphoma
Small cell / oat cell carcinoma


The small blue cells indicate a "LEMON" tumor.

L = leukemia / lymphoma
E = Ewing's / primitive neuroectodermal
M = muscle (rhabdomyosarcoma) or (in the neuraxis) medulloblastoma
O = oat cell (or other small cell)
N = neuroblastoma

The alveolar-like arrangement of the cells is a giveaway for alveolar rhabdo. In most alveolar rhabdos, the fibrovascular septa around each alveolar-like group is better-developed than it is here. Some pathologists would call this the "solid" variant, which is molecularly and clinically about the same.

Don't feel bad if you over-ordered the immunoperoxidase stains. There's a fair amount of variability in staining these LEMON tumors and we have to be certain.

Today, the workup of an alveolar rhabdomyosarcoma will include a search for one of the signature translocations such as PAX3/FOX01.

The fact that Junior has neurofibromatosis is a coincidence. Don't let this kind fored herring give you tunnel vision.

We don't know the outcome of this case, but today Junior has about a 25% chance of a cure with chemotherapy. In the past, these were all lethal.

Sanam Vakassi KCUMB '15

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PAX3/FOX01 FISH translocation
from "Human Pathology"

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