Tuesday, July 19, 2016

The signature feature of sparsely granulated growth hormone pituitary adenoma: the fibrous body

The patient is a middle-aged female with subtle signs of acromegaly.

Arrows point to the pale balls in this pituitary adenoma  which correspond to
fibrous bodies on CAM 5.2 immunohistochemistry

The signature feature of sparsely granulated GH adenomas is the finding of widespread, ball-like, cytoplasmic ‘fibrous bodies’ on CAM5.2  in >70% of cells.

CAM 5.2 immunohistochemistry

Monday, July 18, 2016

A 60-year-old man presents with acute confusion, aggressive behavior, and aphasia


T2-weighted FLAIR MRI 

A 60-year-old man presents with acute confusion, aggressive behavior, and aphasia. Imaging reveals a heterogeneously enhancing mass (5 x 2 x 2 cm) in the left medial temporal lobe with extensive peripheral edema (image above), but no significant contrast enhancement. A subtotal temporal lobectomy was performed on suspicion of a low-grade glioma.


High-power view of biopsy from left temporal lobe

The diagnosis is herpes simplex encephalitis. PCR amplification of DNA from the specimen more specifically identified the causative agent as herpes simplex virus, type 1 (HSV1). The most common identifiable cause of viral encephalitis in hospitalized patients, HSV1 classically exhibits tropism for the orbitofrontal and temporal lobes bilaterally, but can on occasion present as a unifocal mass mimicking neoplasm as exemplified in this case. Untreated cases have a mortality rate of up to 70%, while in patients treated with a 14- to 21-day course of acyclovir the mortality rate is less than 10%. Although the patient in this case clinically improved while on a four-week course of acyclovir, he did not return to baseline functioning and was discharged to a nursing home.

Primary infection with HSV1 is usually subclinical. Symptomatic primary infection may manifest as gingivostomatitis, pharyngitis, or a mononucleosis-like syndrome. During the initial infection, the virus undergoes retrograde transport along sensory axons and becomes established in latent form in sensory ganglia, especially the trigeminal ganglion. Reactivation of latent virus produces recurrent mucocutaneous lesions most commonly involving the vermilion border of the lips (herpes labialis) that are recognized as cold sores or fever blisters. About one-third of herpes encephalitis cases are associated with primary infection, while the remainder result from reactivation of latent virus. It remains unclear whether viral reactivation occurs within the brain itself (herpes simplex viral DNA has been detected in normal brain) or in peripheral sensory ganglia, such as the trigeminal ganglion, with secondary axonal transport to the CNS. Olfactory pathways are also likely routes of retrograde viral transport. In contrast, HSV2 infection is more commonly encountered in newborns, acquired via genital infection from the mother during vaginal birth.

A hypercellular specimen with reactive astrocytes and occasional mitotic figures can raise the specter of astrocytoma. However, demonstration of extravasated blood and ischemic necrosis with infiltration by neutrophils, lymphocytes, and CD68-positive macrophages leads to a diagnosis of hemorrhagic necrotizing encephalitis.  Although the presence of haloed Cowdry A viral inclusions provide diagnostic reassurance (see photomicrograph), they are not always seen and are not specific to HSV. Immunohistochemistry for HSV1/2 is positive in infected cells.

Diagnosis:  Herpes simplex virus type 1 (HSV1) encephalitis

Tuesday, July 12, 2016

This tumor could possibly be 50 years old

Ganglioglioma, WHO grade I
A 70-year-old gentleman presents with a temporal lobe mass. He was diagnosed with a seizure disorder way back when he was 20 years old, and has been on Dilantin since then. Over all these intervening years, he never underwent imaging -- until now. Breakthrough seizures prompted an MRI which showed a well-circumscribed solid and cystic mass. In retrospect, this indolent tumor may well have been present for decades.

Monday, July 11, 2016

What is the current status of "atypical pituitary adenoma"?

What is the current status of "atypical pituitary adenoma" as a distinct entity? Currently, that designation remains in flux. Originally defined in the 2004 WHO Classification of Tumors of Endocrine Organs as a pituitary adenoma with "excessive" p53 immunoreactivity and a MIB1 proliferation index greater than 3%, the entity known as "atypical pituitary adenoma" has over time fallen into some disfavor. Since the literature on this entity is still evolving, some neuropathologists (including me) prefer to sign out such cases as "pituitary adenoma with elevated MIB1 proliferative index" with a comment suggesting that closer-than-usual clinical follow-up might be warranted. Finessing the diagnosis in this way may help the patient avoid automatic administration of radiation therapy while lowering the decision threshold to administer radiation at first recurrence.As for p53, use of that immunohistochemical index is even more controversial with some neuropathologists (including me) eschewing its use entirely in the setting of pituitary adenoma.


Reference:
Kleinschmidt-DeMasters BK, Lopes MB, Prayson RA. An algorithmic approach to sellar region masses. Arch Pathol Lab Med. 2015;139(3):356-372.

Wednesday, July 6, 2016

"Incipient" microvascular proliferation in an anaplastic astrocytoma

At my institution, we require endothelial cells to be layered at least three cells thick to qualify as true microvascular proliferation. This example from an anaplastic astrocytoma, with plump endothelial cells circled,  does not meet that criterion. 

Friday, July 1, 2016

Does IDH1 immunohistochemistry have a slight cross reactivity with IDH2 mutation?

IDH1 immunohistochemistry

This WHO grade II oligodendroglioma had a slight blush of positivity for IDH1. Subsequent mutational analysis revealed an IDH2 mutation. It makes you wonder whether there is a slight cross reactivity of the immunohistochemical stain for IDH2 mutation. Anyone else have this experience?

Thursday, June 30, 2016

Best Post of June 2016: Neuropathologist calls into question the capacity of small centers to adequately diagnose brain tumors in the molecular age

The next in our "Best of the Month" series comes from June 7, 2016:

With the emphasis on molecular diagnostics in the new WHO classification of tumors, an Austrian neuropathologist has called into question the capacity of smaller community hospitals, which don't have access to molecular techniques, to provide adequate diagnoses for many primary brain tumors. In an interview with the Science Daily website, Viennese neuropathologist Johannes Hainfellner (pictured) states: "Modern, advanced medical diagnosis of brain tumors relies heavily on the expertise of academic neuropathology. For this reason, smaller centers treating smaller numbers of cases and with standard pathology facilities without the benefit of university neuropathology have neither the requisite capacity nor the necessary routine." Hainfellner was a contributor to the new WHO book and has a research focus on biomarker validation and translation at the Medical University of Vienna.