Website cases:

• Case 221
• Case 544
• Case 523
• Case 390

CASE NUMBER 221
(no virtual slide for this case)

Clinical History:  A 62-year-old man underwent total nephrectomy for renal cell carcinoma and subsequently received adjuvant chemotherapy. While on chemotherapy, he became leukopenic and thrombocytopenic. He presented to his oncologist with a 3-day history of a rash on his left side.

221-1. What is the differential diagnosis?

Image Gallery:

Physical exam questions:

• Describe the rash seen on the patient’s side.

Microscopy still image questions:

On an annotated screenshot of the microscopy images on the website identify:
1) the epidermis and dermis
2) areas of the epidermis that display necrosis; and
3) features supportive of viral cytopathic change.

Differential Diagnosis questions:

221-1a. What is the differential diagnosis based on the clinical history and physical exam?

221-1b. What is the final diagnosis and why?

221-2. Which of the following is the etiologic agent for this disease?

1. Cytomegalovirus
2. Herpes simplex virus-2
3. Human papilloma virus, type 6
4. Poliovirus
5. Varicella-zoster virus

221-3. Where is latent infection established following primary infection?

1. Dorsal root ganglia
2. Motor axons
3. Neuromuscular junction
4. Peripheral sensory nerves
5. Skeletal muscle

221-4. Which of the following is a rare complication that can be seen in this disease?

1. B-cell lymphoma
2. Facial hemiparesis
3. Myocarditis
4. Toxic shock syndrome
5. Vegetations on heart valves

CASE NUMBER 544
(no virtual slide for this case)

Clinical History:  A 5-year-old boy is brought to the pediatrician because his parents notice that he walks on his toes and has difficulty climbing stairs. They state that he did not begin walking until he was 18 months old. Physical exam reveals bilaterally enlarged calves. A muscle biopsy is performed.

Differential Diagnosis questions:

544-1b. What is the differential diagnosis following physical exam?

Image Gallery:

Microscopy still image questions:

• Describe the findings of the muscle biopsy.
• Which features are supportive of abnormal muscle histology?
• What does the immunohistochemical stain tell you about the diagnosis?

Clinical History, part 2 (click here to move on to part 2)

CASE NUMBER 523, part 1- slide courtesy of UMich
[DigitalScope]

Clinical History:  An 18-year-old man presents for his Army physical. The doctor notices multiple skin lesions distributed evenly across his body and irregular areas of hyperpigmentation. The patient states that he has had these lesions his entire life but that they had never bothered him. One of the lesions is biopsied.

Differential Diagnosis questions:

523-1a. What is the differential diagnosis based on the physical exam?

523-1b. What is the final diagnosis and why?

Image Gallery:

Physical exam image questions:

• Describe the skin lesions shown in the two clinical images.
• What is your differential diagnosis based on these lesions?

VM image questions:

• Describe the virtual microscopic image.
• What shape are the cells?
• Is the process circumscribed or infiltrative?
• Do you see mitotic figures?
• Is this likely benign or malignant?

523-2. A mutation in a gene encoding which of the following is most commonly observed in patients with this disease?

1. Dystrophin
2. E-cadherin
3. Merlin
4. Neurofibromin
5. Tuberin

523-3. Identification of which of the following is highly suggestive of this diagnosis?

1. Hemangioblastoma
2. Meningioma
3. Plexiform neurofibroma
4. Solitary cutaneous neurofibroma
5. Vestibular schwannoma

CASE NUMBER 523, part 2- slide courtesy of UMich
[DigitalScope]

Clinical History (continued): Ten years later, the patient presents to his primary care physician with a 3-week history of “burning” and “shooting” nerve pain in his right arm.  MRI revealed a 5 cm mass within the brachial plexus. The mass was excised.

Differential Diagnosis questions:

523-4b. What is the differential diagnosis with the addition of the imaging studies?

523-4c. What is the final diagnosis and why?  

Image Gallery:

VM image questions:

1. Describe the microscopic image. How does this microscopic section compare to the earlier biopsy?
2. Find a mitotic figure and annotate (don’t spend more than 10 minutes looking!).
3. Is there necrosis? How great is your concern that this is malignant? Why?

523-5. Which of the following is the life-time risk for developing this type of tumor in a patient with this disease?

1. <1%
2. 1 – 10%
3. 21 - 30%
4. 51 - 60%
5. >90%

CASE NUMBER 390- slide courtesy of UMich
[DigitalScope]

Clinical History: A 58-year-old man presented to his primary care physician with a 3-month history of blurred vision in his left eye. Previously, he had 20-20 vision in both eyes and had not seen an ophthalmologist since he was in college. A fundoscopic exam is performed.

Ultrasonographic examination confirmed a diameter of 10 mm with a thickness of 3.5 mm.  Following discussion, treatment options including radiation therapy and enucleation  were discussed, but the patient declined. Ten months later, he presented with worsening vision and eye pain and fundoscopic exam revealed that the lesion had progressed. At this point, the patient agreed to enucleation.

Image Gallery:

There is a pigmented lesion near the fovea of the left eye.

There is a tumor mass within the globe of the eye. The lesion is cellular, composed of spindled to epithelioid cells. There are scattered foci of melanin pigment. The cells have large nucleoli, a classic feature in melanoma. Mitotic figures are hard to find. No necrosis is present.

Review Eye Histology

Review Eye Anatomy Renal Anatomy NetID login required (click here if not already logged in)

Fundoscopy image questions:

• Describe the findings on the fundoscopic exam.
• Take a screenshot and annotate the lesion, the optic disk and the fovea for each eye.
• What would your differential diagnosis be based on the fundoscopic exam?

VM image questions:

• Take a screenshot of the VM slide and annotate the following components of the retina:
  • the inner limiting membrane,
  • inner plexiform layer,
  • inner nuclear layer,
  • outer plexiform layer and
  • outer nuclear layer (the outer segments of the rods and cones are a bit hard to see, so also indicate where they WOULD be).
• Describe the lesion. Identify an area with spindle cells and an area with epithelioid cells. Identify melanin pigment.

Differential Diagnosis questions:

390-1a. What is the differential diagnosis based on the patient’s initial presentation?

390-1b. What is the differential diagnosis following the fundoscopic exam?

390-1c. What is the final diagnosis and why?

390-2. Which oncogene is most commonly mutated in this disease?

1. BAP1
2. CFH
3. GNAQ
4. RHO
5. USH2A

390-3. Which feature is associated with worse prognosis in this disease?

1. Depth of invasion
2. Lateral extent of tumor
3. Origination in the iris
4. Spindle cell morphology
5. Ulceration

390-4. Which of the following is the most common site of metastasis for this tumor?

1. Bone
2. Brain
3. Liver
4. Lung
5. Soft tissue

MUSCLE PATHOLOGY Review Items

Muscle Pathology Key Vocabulary Terms (click here to search any additional terms on Stedman's Online Medical Dictionary)

Eye Pathology Key Vocabulary Terms (click here to search any additional terms on Stedman's Online Medical Dictionary)

PNS: GOALS and LEARNING OBJECTIVES

Goal: Neuromuscular  and Muscular Disorders
Apply knowledge of clinical, anatomic and neuropathologic principles to the diagnosis of neuromuscular and muscular disorders.

• Objective 1: Amyotrophic Lateral Sclerosis
  Describe the etiology, pathogenesis, and clinical features of amyotrophic lateral sclerosis.
• Objective 2: Mitochondrial Disorders
  Describe the etiology, pathogenesis, and clinical features of mitochondrial diseases affecting muscle.
• Objective 3: Muscular Dystrophies
  Compare and contrast the etiology, pathogenesis, and clinical features of the dystrophiopathies.
• Objective 4: Acquired Disorders of Skeletal Muscle
  Compare and contrast the etiology, pathogenesis, and clinical features of inflammatory myopathies and toxic myopathies.

Goal: Pathology of Peripheral Nerves
Apply knowledge of clinical, anatomic and neuropathologic principles to the diagnosis of neural disorders.

• Objective 1: Disorders Associated with Peripheral Nerve Injury
  Compare and contrast the peripheral neuropathies in terms of etiology, risk factors, clinical presentation, pathologic findings and natural history.
• Objective 2: Disorders of the Neuromuscular Junction
  Compare and contrast the disorders of the neuromuscular junction in terms of etiology, risk factors, clinical presentation, pathologic findings and natural history.
• Objective 3: Peripheral Nerve Sheath Tumors
  Compare and contrast benign and malignant tumors of the peripheral nerve sheath in terms of etiology, genetics, associated syndromes, clinical presentation, pathologic findings and prognostic factors.