Microcystic adenocarcinoma of the prostate-pseudobenign carcinoma

Reference :

Microcystic Adenocarcinoma of the Prostate: A Variant of Pseudohyperplastic and Atrophic Patterns : Yaskiv, Oksana et al.
The American Journal of Surgical Pathology: April 2010 - Volume 34 - Issue 4 - pp 556-561

Do you see anything in this prostate that's worrisome for malignancy?

dilated glands admixed with small acini in a nodule

I don't, at least not at this power, and yet this is an example of "microcystic" adenocarcinoma of the prostate. Higher power will show clear-cut cytologic features of malignancy.
If this doesn't concern you about the risk of scanning prostate slides at 4x, it should!

Microcystic adenocarcinoma with dilated and crowded glands displaying a predominantly flat lining layer

Microcystic adenocarcinoma with jumbled arrangement of dilated malignant glands.

Microcystic adenocarcinoma with atrophic features.

Dilated malignant glands with adjacent usual small acinar adenocarcinoma glands for size reference

Numerous crystalloids in dilated glands of microcystic adenocarcinoma.

Nuclear atypia with prominent nucleoli in the lining layer of 2 microcystic adenocarcinoma glands.

Microcystic adenocarcinoma extending into periprostatic adipose tissue, along with several small acinar adenocarcinoma glands.

Overerexpression of α-methylacyl CoA racemase in microcystic adenocarcinoma, with luminal accentuation. No basal cells are detected with this p63/AMACR cocktail immunohistochemical stain.

Overexpression of AMACR with granular cytoplasmic signal in microcystic adenocarcinoma gland with basal cell absence (right). Internal control benign atrophic glands on left show basal cell presence, with p63 marker, and lack of AMACR staining.

Basal cell absence in microcystic adenocarcinoma (left) compared with benign atrophic glands with basal cells (right), as assessed with 34βE12 immunostain.

Microcystic adenocarcinoma in needle biopsy tissue

Reference :

Microcystic Adenocarcinoma of the Prostate: A Variant of Pseudohyperplastic and Atrophic Patterns : Yaskiv, Oksana et al.The American Journal of Surgical Pathology: April 2010 - Volume 34 - Issue 4 - pp 556-561

Cystic glandular dilatation is a common finding in benign prostatic tissues, being identified in benign prostatic hyperplasia (BPH) in the transition zone and as cystic atrophy in the peripheral zone. Diagnostic awareness that acinar prostatic adenocarcinoma may exhibit cystic dilatation is important to avoid underdiagnosis of prostatic adenocarcinoma.

Cystic change in adenocarcinoma of the prostate is unusual and may be confused with benign cystic atrophy.Microcystic adenocarcinoma of the prostate is a distinctive histomorphologic presentation of prostatic adenocarcinoma that is deceptively benign-looking at low magnifications.

Detection of intraluminal crystalloids or wispy blue mucin at low magnification, immunostains for α-methylacyl CoA racemase, and basal cells, and a search for adjacent usual small acinar adenocarcinoma are helpful diagnostic aids. Diagnostic awareness of this growth pattern of prostatic carcinoma is important to avoid underdiagnosis of adenocarcinoma of the prostate.

High Grade Prostatic Intraepithelial Neoplasia (HGPIN)

High Grade Prostatic Intraepithelial Neoplasia (HGPIN):
Common questions asked about HGPIN are :
-How do we as pathologists make these diagnoses?
-What do they mean for the patient in terms of cancer risk?
-What is/are the optimal strategies for follow-up so that if cancer does eventually develop it is caught at an early, curable stage?

Pathology criteria for diagnosis of HGPIN:

-Architecturally benign acini/ducts lined by atypical cells.
-These cells show large nuclei and prominent nucleoli (cytologic features of carcinoma).
-Generally at least 10% of the luminal cells should show these features to make the diagnosis.


Diagnosis of HGPIN has been shown to be reproducible. Low grade prostatic intraepithelial neoplasia has poor reproducibility (even among experts), ill defined diagnostic criteria, and no true clinical relevance. It is for these reasons that I do not personally diagnose LGPIN.

Risk of subsequent cancer:

-In previous studies the risk of carcinoma on follow-up biopsy for a HGPIN diagnosis has been reported to be as high as 50%, however, when the data is based on series with increased case numbers, this decrease to around 25%.

-Number of cores with high grade PIN predicts risk of subsequent cancer (1 core-30%, 3 cores-40%, 4+ cores-75%).In addition, morphologic patterns of HGPIN (i.e. flat, tufted, micropapillary, cribriform) have not been shown to be predictive of subsequent carcinoma.

Follow up strategy for patients with HGPIN:

Although there have been several follow-up strategies for patients with a diagnosis of HGPIN, many recommend re-biopsy within 3-6 months. One protocol includes biopsies at 3-6 months for 2 years, followed by yearly biopsies for life.
In a recent study, recommendation was made that in the absence of other clinical indicators worrisome for cancer, men do not need a routine repeat biopsy within a year following a HGPIN diagnosis. As the natural history of HGPIN in any given patient is not known, the decision to take additional biopsies past 1 year is best made on a patient by patient basis with a frank discussion between the physician and patient.

Various studies have shown that in patients with prior diagnosis of HGPIN, cancer is often diagnosed in adjacent sites and even within the contralateral lobe. It is for this reason that when re-biopsy is performed for HGPIN sampling should be concentrated in the region of the previous HGPIN with the rest of the gland sampled so as not to miss small foci of cancer. Specimens should be meticulously labeled as to site (in addition to patient identification) and optimally no more than 2 cores should be submitted per container.

Summary:

1. HGPIN is characterized by architecturally benign glands lined by cells which are morphologically similar to prostate cancer, and is the putative precursor of prostate cancer.

2. Unlike HGPIN the diagnosis of LGPIN is not reproducible and carries no clinical significance.

3. While earlier reports described the risk of cancer following a diagnosis of HGPIN as high as 50%, more current reviews suggest that the risk may be much lower.

4. Men with a diagnosis of HGPIN (especially those with HGPIN focally) may not need re-biopsy for up to one year after initial diagnosis. Repeat biopsies should concentrate on the area of previous HGPIN, but also include sampling of the entire gland.
(Thanks to Dr.Dharam Ramnani for allowing to use the above images for this site.)
References:
1. Epstein JI, Herawi M. Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: implications for patient care. The Journal of Urology 2006; 175: 820-834.
2. Bishara T, Ramnani DM, Epstein JI. High grade prostatic intraepithelial neoplasia on needle biopsy risk of cancer on repeat biopsy related to number of involved cores and morphologic pattern. The American Journal of Surgical Pathology 2004; 28: 629-633.
3. Bostwick DG, Qian J. High-grade prostatic intraepithelial neoplasia. Modern Pathology 2004; 17: 360-379.

Desmoplastic melanoma, a common missed diagnosis.

Introduction:

Although desmoplastic melanoma represents less than 2 percent of all melanomas, it's frequently misdiagnosed, due to a lack of distinctive clinical presentation features. Histologic diagnosis is rarely straightforward either.

Patients are often middle age-to-elderly and present with the tumor most often on the head and neck region. The lesion may resemble a scar as it is often a hard nodule or plaque.
Pigmentation is variable but often absent. The tumor has ill-defined margins and is very infiltrative, making local control difficult. Sentinel lymph node excision is routinely performed but rarely positive.

Histology :
The histology can also masquerade as a scar . The epidermis is often atrophic and may or may not have a precursor (in situ) lesion. Characteristically, the tumor is in the dermis as spindled melanocytes resembling fibroblasts.Often, there is an edematous or desmoplastic stroma with
scattered lymphoid aggregates. Perineural invasion is common.In about one third of the lesions, there are foci of epithelioid or conventional melanoma.

S-100 and HMB45 immunohistochemical stains can help differentiate tumor from scar.
At low power, there is a fibrotic lesion in the dermis with scattered lymphoid aggregates.

The lesion is paucicellular, but there is cellular atypia .

Reporting of the histologic subtype of melanoma is common practice, but it is unclear what impact, if any, it has on management decisions. One possible exception is desmoplastic melanoma, a distinct subtype with a unique biologic behavior. It is now recognized that desmoplastic melanomas present with greater tumor thickness (Breslow level) than their conventional counterparts but fail to demonstrate a corresponding higher sentinel lymph node involvement or higher mortality.

Some authors have further subdivided desmoplastic melanomas into "pure" and "mixed" forms. Pure (primarily fibrotic) and mixed varieties, which include features common to conventional melanoma and desmoplastic areas. As per these recent studies only 1% of pure desmoplastic melanomas metastasized to regional lymph nodes compared to 10% with mixed histology.

References:
1. Attis MG, Burchette JL, Selim MA, et al. Differential expression of N-cadherin distinguishes a subset metastasizing desmoplastic melanoma.
2. Davison JM, Rosenbaum E, Barrett TL, et al. Absence of V599E BRAF mutations in desmoplastic melanomas. Cancer. 2005 103:788.
3. Hawkins WG, Busam KJ, Ben-Porat L, et al. Desmoplastic melanoma:a pathologically and clinically distinct form of melanoma. Ann Surg Oncol. 2005 12:207.