high-grade PIN

WPA

Definition: High grade PIN is characterized by a more uniform morphologic alteration. High-grade PIN consists of intermediate to large size preexisting glands with proliferative changes resulting in hyperchromatic appearance.

High grade PIN has atypical cells, and a basal cell layer. Cytologic features of HGPIN include prominent nucleoli and an increased nuclear size and N/C ratio. Low grade PIN has less prominent nucleoli. Architecturally it may be cribriform, tufted, micropapillary or flat.

See also : low grade PIN / low-grade PIN

Images

 High grade PIN

• Webpathology: http://www.webpathology.com/image.asp?n=1&Case;=19
• https://www.flickr.com/photos/131965750@N06/17538084641
• https://www.flickr.com/photos/131965750@N06/1735045127

 Flat high grade PIN

• https://www.flickr.com/photos/131965750@N06/21797798264
• https://www.flickr.com/photos/131965750@N06/22232572620

 Cribriform high grade PIN

• https://www.flickr.com/photos/131965750@N06/18675680769

Cytologically, the acini and ducts are lined by malignant cells with a variety of architectural complexity and patterns. The individual cells are almost uniformly enlarged with increased nuclear/cytoplasmic ratio, therefore showing less variation in nuclear size than that seen in low grade PIN.

Many cells of HGPIN contain prominent nucleoli and most show coarse clumping of the chromatin that is often present along the nuclear membrane.

HGPIN can be readily appreciated at low power microscopic examination by virtue of the darker "blue" staining of the lining that reflects the expanded nuclear chromatin area.

High-grade PIN consists of intermediate to large size preexisting glands with proliferative changes resulting in hyperchromatic appearance. Note the small foci of cancer adjacent to PIN on the upper left and lower right.

Six variants of high-grade PIN have been described:
 tufted variant of high-grade PIN
 micropapillary variant of high-grade PIN

• The acinar epithelial cells are arranged in long, delicate, finger-like structures in this micropapillary variant.

 flat variant of high-grade PIN

• The acinar epithelial cells are pseudostratified and arranged linearly.
• There is nuclear and nucleolar enlargement. Note the prominent apical snouts.

 cribriform variant of high-grade PIN

• In cribriform high-grade PIN interconnecting bridges of acinar epithelial cells extend across the lumen of the glands.
• Distinction of cribriform variant of high-grade PIN from adenocarcinoma may at times be extremely difficult.
• Immunostain for high molecular weight cytokeratin 34bE12 may be useful in such cases – basal cell layer is fragmented in PIN and absent in adenocarcinoma.
• The benign glands have continuous basal cell layer; high-grade PIN glands have fragmented basal cell layer; malignant glands completely lack basal cell layer.

 small cell variant of high-grade PIN
 inverted variant of high-grade PIN

Synopsis

 High-grade PIN consists of intermediate to large size preexisting glands with proliferative changes resulting in hyperchromatic appearance.
 enlarged nuclei
 prominent nucleoli
 residual basal cells.
 The acinar epithelial cells are pseudostratified and arranged linearly.
 There is nuclear and nucleolar enlargement.
 prominent apical snouts.
 intermediate-to-large size preexisting glands display nuclear and nucleolar enlargement and fragmented basal cell layer.

Differential diagnosis

 basal cell hyperplasia

• Basal cell hyperplasia is surrounded by a well organized basal cell layer and stroma without desmoplasia.
• No atypical mitotic figures are present, and benign prostate glands are embedded within the the benign cellular proliferation.
• By IHC, basal cells stain for HMWCK (CK903/ 34BE12) and p63.

 cribriform clear cell hyperplasia

• The cells of CCCH are cytologically benign, they lack prominent nucleoli and do not have an increased N/C ratio.
• The lesion shows a basal cell layer and papillary growth of glands with clear to eosinophilic cells with prominent cribriforming.

 prostatic denocarcinoma

• Prostatic adenocarcinoma shows prominent nucleoli and an increased nuclear size and N/C ratio.
• There is an absent basal cell layer, and glands tend to be rounded rather than tufted.
• Definitive features of prostatic adenocarcinoma include perineural invasion, collagenous micronodules / mucinous fibroplasia, and glomerular forms.
• It is negative for p63 (usually) and CK903, and positive for AMACR / racemase.

 prostatic squamous cell carcinoma / prostatic SCC

• SCC shows cellular atypia and frequently shows keratinization.