Amyloidosis is characterized by extracellular deposition of abnormal protein. There are six types: primary, secondary, hemodialysis-related, hereditary, senile, and localized. Primary (AL) amyloidosis is associated with monoclonal light chains in serum and/or urine with 15% of patients having multiple myeloma. Secondary (AA) amyloidosis is associated with inflammatory, infectious, and neoplastic diseases. The presentation is protean, including macroglossia, a dilated and atonic esophagus, gastric polyps or enlarged folds, and luminal narrowing or ulceration of the colon. Amyloid deposition in the gastrointestinal (GI) tract is greatest in the small intestine. The symptoms include diarrhea, steatorrhea, or constipation. Pseudo-obstruction carries a particularly grave prognosis, often not responding to pro-motility agents. Hepatic involvement is common, but the clinical manifestations are usually mild with hepatomegaly and an elevated alkaline phosphatase level. Biopsies to diagnose amyloidosis can be taken from the fat, kidney, intestine, or bone marrow. The safety of liver biopsies is controversial. With Congo Red stain, amyloid appears red in normal light and apple-green in polarized light. Treatment for AL amyloidosis is chemotherapy and stem cell transplantation; treatment for AA amyloidosis is control of the underlying disease. Amyloidosis should be considered in patients with proteinuria, cardiomyopathy, hepatomegaly (with mildly abnormal liver tests), peripheral and autonomic neuropathy, weight loss, and GI symptoms.

Intraductal carcinoma of the prostate and high grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care, but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically-identified intraductal carcinoma, PIN or borderline intraductal proliferations more concerning than PIN, but falling short of morphologic criteria for intraductal carcinoma. Intraductal carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated intraductal carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had carcinoma in a subsequent needle biopsy specimen, compared to 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified intraductal carcinoma yet is very rare in high grade PIN. Borderline intraductal proliferations, especially those with PTEN loss, have a high rate of carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish intraductal carcinoma from high grade PIN in this setting.

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Stromal tumors of uncertain malignant potential (STUMPs) are rare tumors characterized by an atypical, unique stromal proliferation of the prostate. Various stromal proliferations of STUMPs have been described; however, epithelial proliferations occurring within the STUMP have not been systematically described to date. We reviewed 89 cases of STUMP from our consultation service from 1990 to 2010. Nineteen cases without a glandular component were excluded. We next evaluated the glandular component of the remaining 70 cases of STUMP for glandular crowding and complexity, prostatic intraepithelial neoplasia (PIN), squamous metaplasia, urothelial metaplasia, basal cell hyperplasia, adenosis, and clear cell cribriform hyperplasia. In 58 cases (83%), the glandular component differed from glands on the same biopsy specimen uninvolved by STUMP. The most common abnormalities were glandular crowding in 35 of 70 (50%) and a very prominent basal cell layer in some glands in 32 of 70 (46%) cases. The next most frequent glandular variation from normal was prominent papillary infolding in 13 of 70 (19%) cases. Less-frequent epithelial changes within the STUMP were as follows: 10 of 70 (14%) showed cystically dilated glands; 7 of 10 (10%) had basal cell hyperplasia; 6 of 70 (9%) had urothelial metaplasia; 6 of 70 (9%) showed squamous metaplasia; 3 of 70 (4%) had cribriform hyperplasia; 3 of 70 (4%) had adenosis; and 1 case each showed high-grade PIN, low-grade PIN, and partial atrophy. The glandular component of STUMP was histologically normal in 12 (17%) cases. There was a tendency toward urothelial and squamous metaplasia in STUMPs with a phyllodes pattern, and a prominent basal cell layer in STUMPs with degenerative and cellular stroma. This is the first study to systematically describe the epithelial proliferations occurring in STUMP. This study suggests that, within STUMPs, there is epithelial-mesenchymal crosstalk, as has been described in benign prostate and in prostatic carcinogenesis. In unusual cases of STUMP, the epithelial proliferation may predominate to the extent that it can mask the diagnosis of STUMP.