Case Study 56

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Case Study 56

• Kenneth Clark, MD

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Question 1

• This is a 59-year-old Caucasian woman with a
  history of granulomatous nephritis (diagnosed 7
  years prior), myelodysplastic syndrome, and
  common variable immunodeficiency with
  progressively worsening dizziness, blurry vision
  and headache. Workup at an outside hospital
  revealed a sellar mass along with
  panhypopituitarism, adrenal insufficiency and
  hypothyroidism.
• Describe the MRI findings.

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(No Transcript)
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Answer

• Symmetric enlargement of pituitary gland and
  infundibulum with mild homogeneous enhancement.
  No areas of T2 or T2 FLAIR signal abnormality are
  evident.

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Question 2

• What is the differential diagnosis of a sellar
  lesion?

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Answer

• Pituitary Adenoma
• Craniopharyngioma
• Meningioma
• Pituitary Carcinoma
• Pituicytoma
• Oncocytoma
• Granular Cell Tumor
• Lymphocytic Hypophysitis
• Granulomatous Hypophysitis
• Metastatic Disease (rare)

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Question 3

• What are the common signs and symptoms of sellar
  lesions (tumors or inflammatory)?

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Answer

• Headaches (non-specific)
• Double Vision (non-specific)
• Loss of Peripheral Vision Bitemporal
  Hemianopsia (non-specific)
• Facial Pain and Numbness (non-specific)
• Symptoms related to hormonal abnormalities
• lack of energy
• weight loss, nausea, vomiting, constipation
• amenorrhea and infertility
• dry skin, increased pigmentation of the skin
• cold intolerance
• mental status changes sleepiness, psychosis

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Question 4

• The lesion was resected. Describe the findings.
• Click here to view the slide

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Answer

• The tissue shows near complete effacement of
  pituitary architecture by a rich
  lymphohistiocytic infiltrate. The histiocytes
  have large irregularly shaped nuclear with
  prominent nucleoli and finely distributed pale
  blue chromatin. The cytoplasmic borders are
  completely indistinct, resulting in a syncytial
  appearance of groups of histiocytes. Small
  numbers of small monomorphic lymphocytes are
  positioned around the periphery of the histiocyte
  collections. Small randomly isolated nests of
  polytypic pituitary cells are seen randomly
  distributed throughout the specimen.

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Question 5

• What is your diagnostic impression?

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Answer

• The lesion appears to be inflammatory in nature
  rich in histiocytes either infectious or
  idiopathic in etiology. It does not appear to be
  neoplastic, although lymphoma cannot be entirely
  ruled out at this point.

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Question 6

• What immunohistochemical and/or special stains
  would be helpful in confirming your initial
  impression of this lesion?

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Answer

• Inflammatory Cell Markers
• CD3 (T-cells)
• CD20 (B-cells)
• CD68 (macrophages, histiocytes)
• GFAP, IDH1 (to rule out an unusual glial process)
• Synaptophysin (to ascertain the pituitary
  element)
• Reticulin (to evaluate residual pituitary
  structure/architecture)
• Click to view CD3, CD68, Reticulin

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Question 7

• Based on the results of the stains (see below)
  and HE slides, what is the general diagnostic
  category?
• CD3 - highlights numerous small mature
  lymphocytes
• CD20 - very rare positive b-lymphocytes
• CD68 - strong staining in numerous histiocytes
  highlights ill-defined granuloma formation
• Synaptophysin - positive in sparse scattered
  small nests of pituitary cells highlights
  architectural distortion by histiocytes
• GFAP - rare positive glial cells near periphery
  of lesion
• IDH1 - negative
• Reticulin highlights total effacement of nested
  pituitary architecture

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Answer

• Inflammatory/histiocytic process

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Question 8

• What is the differential diagnosis of a
  non-necrotizing histiocytic / granulomatous
  process?

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Answer

• Neurosarcoidosis
• Infectious (fungal or mycobacterial)
• Langerhans cell histiocytosis
• Erdheim Chester disease
• Rosai-Dorfman disease

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Question 9

• What additional stains would you order to better
  characterize the lesion?

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Answer

• Acid Fast, Grocott (rule out infectious process)
• CD1A S100
• Langerhans cell histiocytosis histiocytes are
  CD1a and S100 positive
• Erdheim Chester disease histiocytes are S100
  negative (usually) and CD1a negative
• Rosai Dorfman disease histiocytes are S100
  positive and CD1a negative
• Sarcoidosis has similar staining profile of ECD

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Question 10

• The results of the additional stains are as
  follows
• S100 shows sparsely scattered background
  folliculo-stellate cells negative in histiocytes
• CD1a negative
• Grocott negative
• Acid Fast negative
• What is your diagnosis?

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Answer

• Non-necrotizing granulomatous hypophysitis, favor
  neurosarcoidosis

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Question 11

• Why favor sarcoidosis when Erdheim Chester
  disease has a similar histologic appearance and
  immunohistochemical profile? Explain.

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Answer

• ECD, which is far more rare than sarcoidosis
  (300-400 reported cases worldwide), is also
  called polyostotic sclerosing histiocytosis
  because it most often involves long bones.
  Because this patient had a history of
  non-necrotizing renal granulomas and no bone
  lesions it is much more likely that this
  represents sarcoidosis involving the pituitary
  than ECD. Furthermore, ECD has a progressive and
  usually fatal course in cases with extra-osseous
  involvement and is not responsive to steroid
  therapy if this patient had ECD at the time of
  her renal biopsies her clinical course would
  likely have been much more aggressive and
  probably fatal. Histologically, ECD lesions often
  show Touton-like giant cells and are rich in
  eosinophils neither of which are seen in this
  lesion. Considering the clinical AND
  histopathologic elements of this case, it seems
  that sarcoidosis is more likely than ECD.

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References

• Veyssier-Belot C, Cacoub P, Caparros-Lefebvre D,
  Wechsler J, Brun B, Remy M, Wallaert B, Petit H,
  Grimaldi A, Wechsler B, Godeau P (1996)
  ErdheimChester disease. Clinical and Radiologic
  Characteristics of 59 Cases. Medicine
  (Baltimore). 75157169.
• Louis D, Ohgaki H, Wiestler O, Cavanee W. WHO
  Classification of Tumours of the Central Nervous
  System. IARC Lyon 2007.
• Burns T. Neurosarcoidosis (2003). Arch Neurol.
  601166-1168.
• Rosai J. Rosai and Ackermans Surgical Pathology.
  Elsevier 2004.