Do All Prostate Cancers Behave the Same?

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Journal of Cancer Therapy, 2013, 4, 1426-1428

Published Online November 2013 (http://www.scirp.org/journal/jct)

http://dx.doi.org/10.4236/jct.2013.49169

Open Access JCT

Do All Prostate Cancers Behave the Same?

Dissanayake Thusitha1*, Arze Elizabeth2, Rogers Mailien3

1Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, USA;

2Department of Pathology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, USA; 3Division of

Hematology-Oncology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, USA.

Email: *[email protected]

Received August 27th, 2013; revised September 25th, 2013; accepted October 3rd, 2013

Copyright © 2013 Dissanayake Thusitha et al. This is an open access article distributed under the Creative Commons Attribution

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Two different immunohistochemical types suggestive of Large Cell Neuroendocrine (NE) carcinoma and Adenocarci-

noma in a patient with known diffusely metastatic, ho rmone refractory prostate carcinoma are rarities. Interestingly, our

patient had documented history of exposure to Agent Orange during his time of service. The use of routinely used im-

munohistochemical stains for pathological diagnosis was a challenge in this case, though throughout his disease course,

the diagnosis was confirmed as Adenocarcinoma of prostate with biopsies from all various sites of metastases. Systemic

chemotherapy has been historically suboptimal in management of aggressively behaved prostate carcinomas. Finding

any association of Agent Orange as a causative etiology and improving diagnosis and management of such aggressive

hormone refractory prostate carcinoma need further investigations.

Keywords: Large Cell Neuroendocrine Carcinoma; Adenocarcinoma of Prostate; Hormone Refractory Prostate

Carcinoma; Agent Orange

1. Introduction

A 62-year-old white male was diagnosed with metastatic

hormone refractory adenocarcinoma of prostate and was

treated with luteinizing hormone releasing hormone ago-

nist. The patient gave a history of melanoma and remote

history of tobacco abuse. Several months after treatment

was initiated, the patient was presented to the emergency

room for stroke like symptoms and was found to have

brain metastases secondary to his prostate.

Further workup revealed a mediastinal lymph node

wi th inconclusive biopsy result for a primary though adeno-

carcinoma was primarily suspected.

We present an interesting yet complicated case raising

the question of prostate cancer with exposure to Agent

Orange, to which our patient was exposed during the

Vietnam War.

2. Case Report and Discussion

A Vietnam veteran was originally diagnosed with Stage

IV Prostate Adenocarcinoma July 2011 when he pre-

sented with new onset urinary retention.

He underwent cystoscopy July 26th, 2011 and 4 out of

4 core biopsies were reported as adenocarcinoma of

prostate with Gleason score of 8.

His bone scan showed extensive bony metastases.

At the time of diagnosis, his PSA was only mildly

elevated at 5.66. He was started on an drogen depriv ation

therapy (ADT) with Zoladex in jections.

In November 2011, patient presented to VA ER with

vomiting and left sided weakness. On suspicion of cere-

bral vascular accident, CT scanning revealed a 4-cm right

frontal white matter centrally necrotic mass with sur-

rounding vasogenic edema. He was transferred to local

level 4 tertiary care center and brain biopsy performed.

Due to rarity of adenocarcinoma of prostate metasta-

sizing to the brain, search for more common sources

were sought. Further investigation proved his history of

melanoma was actually squamous cell but due to history

of smoking, lung primary was also a possibility.

Pathology of brain biopsies reported as tumor cells

showing sheets of neoplastic cells with prominent gland

and cruciform formation with marked nuclear atypia with

easily visible mitosis. The morphological features were

consistent with prostate adenocarcinoma per pathology

report (Figures 1(a) and (b)).

The submitted PSA immunohistochemical stains at the

outside facility were negative which is common after

*Corresponding aut hor.

Do All Prostate Cancers Behave the Same? 1427

(a) (b)

Figure 1. (a) Bran biopsy in low power; (b) Brain biopsy in hi power. The tumor cells show sheets of neoplastic cells with

prominent gland and cribriform formation with marked nuclear atypia. Mitosis is easily visible. The morphologic features

are consistent with prostatic adenocarcinoma, however, the submitted PSA immunohisto-chemical stain performed at the

outside facility is negative.

initiation of ADT. The rest of the submitted slides show-

ed that the tumor cells were strongly reactive for CK7

and negative for CK20 and TTF1. The negative TTF1

made lung and thyroid origin less likely. The outside in-

stitution also performed HMB, MART-1 and G-FAP

immunohistochemical stains. Per report the tumor cells

are negative for HMB and MART-1 which exclude mela-

noma. The tumor cells are also negative for GFAP which

excludes an ependymal and astrocytic lesion [1].

His oncology care was transferred to VA Hematology/

Oncology department in November 2011. Colonoscopy

was performed and revealed negative results so his an-

drogen deprivation therapy was continued through his

disease course. Follow up imaging with MRI spine

showed more bony disease so PET/CT was performed to

exclude new primary.

PET/CT only avid in subcarinal area so endobronchial

ultrasound guided biopsy (EBUS) was performed and

again pathological diagnosis of adenocarcinoma; likely,

prostate as the primary site. Immunohistochemistry re-

ported strongly positive for CK7, focally positive for

CK20, but negative for TTF-1, p63 and PSA.

The patient was started on Docetaxol and prednisone

and had a total of 6 cycles. His treatment was compli-

cated with new neurological symptoms but imaging only

showed increased edema around his previous intracranial

lesion treated with local radiation; cyber knife therapy.

In mid October 2012, assessment which included CT

of Chest with contrast revealed new extensive hepatic

metastasis with the largest lesion measuring of about 7.6

× 7.4 cm which was biopsied under CT guidance. The

pathology reported Immunoperoxidase studies showing

the moderate reactivity of tumor cells with AE1/AE3,

moderate reactivity with chromogranin, moderate to

strong reactivity with synaptophysin and negative reac-

tivity with CD56 (Figures 2 and 3).

Tumor cells also showed moderate to marked reacti-

vity with TTF-1, but are negative for CK7, CK20, PSA

and CD45. Tumor cells also show mild to moderate reac-

tivity with S100 protein. There were no small cells pre-

sent [1].

These immunophenotypic characteristics were consis-

tent with TTF-1 positive large neuroendocrine (NE) car-

cinoma which comprises the small subset of non-small

cell carcinomas. Per pathology report, there is a rare pos-

sibility of large cell neuroendocrine carcinomas with

TTF-1 positivity of genitour inary origin [2,3].

Biopsy slides of subcarinal lymph nodes were again

looked at carefully and revealed a very small population

of TTF-1 positive cells (though this was no t officially do-

cumented anywhere). It appeared there were 2 distinct

clones in his subcarinal metastatic lesions [4].

Within one week of discovery of his hepatic lesions,

he fell very ill and could not be started on any further

chemotherapy and succumbed to his advanced illness.

3. Conclusions

Management of hormone refractory prostate cancer has

been always a challenge in therapy and follow-up for

prognosis. When metastasis occurs, there will be a point

that response to androgen deprivation therapy will de-

cline until one becomes hormone refractory.

Systemic chemotherapy has been historically subopti-

mal in regard to prolonged responses and tolerance.

Markers like PSA have become less useful in this situa-

tion.

Two different immunohistochemical types of cells

from the same biopsy in a veteran with a history of ex-

Open Access JCT

Do All Prostate Cancers Behave the Same?

1428

(a) (b)

Figure 2. (a) Liver biopsy in low power; (b) Liver biopsy in high power. Sections show fragments of fibrovasculer tissue in-

filtrated by a poorly differentiated carcinoma with zonal coagulation necrosis and moderate desmoplastic reaction. Tumor

cells have variable large nucleoli with coarse chromatin, occasional large nucleoli and scant cytoplasm. Mitotic activity is high,

including atypical mitosis and scattered tumor giant cells.

Fi gur e 3. Prostate biopsy . Four out of four core biopsy speci-

mens contain prostatic adenocarcinoma with a predominant

Gleason Grade of 4 + 4 = 8. There is also presented a focal

area with Gleason Grade 5 adenocarcinoma.

posure to Agent Orange are an unusual presentation.

As with our patient, the aggressiveness of the disease

and use of commonly available immunohistochemical

stains for pathological diagnosis can be a challenge.

Finding an association of Agent Orange as a causative

etiology, and improving diagnosis, and management of

such aggressive hormone refractory prostate carcinoma

need further research.

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