Search

Introduction Metastatic prostatic adenocarcinoma (PAC) has mostly involved the pelvic lymph nodes; metastases to the cervical lymph nodes are exceedingly rare. Materials and methods A retrospective review of cytopathology files (January 1990 to March 2019) identified 13 cases of metastatic PAC to cervical lymph nodes diagnosed using fine-needle aspiration biopsy (FNAB). The clinical and demographic information were collected from the electronic medical records, and the slides were reviewed. Results A total of 13 male patients with a mean age at FNAB 69 years (range, 61-86 years); 12 patients had a known history of PAC. In the patient without a history of PAC, the FNAB finding had been misinterpreted as papillary thyroid carcinoma. The interval between the original diagnosis and cervical lymph node metastasis was 98.5 months (range, 1-288 months). Most involved the left side (85%). Most smears had a clean background with few lymphocytes (46%) and numerous cellular clusters in flat sheets and acini (62%) and were composed of polygonal cells (46%) with round-oval shaped nuclei and indistinct cell borders (92%). The cytoplasm was granular (61%) or scanty (46%). The nuclei were uniform, size ≥2 times that of a neutrophil (69%). Prominent nucleoli and anisonucleosis were seen in 54% of cases; cellular pleomorphism was infrequent (30%). Immunostains confirmed the prostate origin in 7 tissue cores. Conclusions Metastatic PAC to the cervical lymph nodes occurs infrequently. If the history is unknown, cases can be misdiagnosed as metastases from cervical neoplasms. The findings indicating metastatic PAC to the cervical lymph nodes on FNAB include involvement of left-sided cervical lymph nodes in elderly male patients and cellular smears composed of uniform polygonal cells, arranged in flat sheets and acini, with granular cytoplasm, indistinct cell borders, and round-oval nuclei with prominent nucleoli.

This image demonstrates an unusual presentation of an adrenal metastasis from prostate cancer detected by 68Ga-prostate-specific membrane antigen PET/CT and confirmed by biopsy. A 68-year-old man with prostate cancer persisted with elevated levels of prostate-specific antigen after radical prostatectomy. Imaging identified a single abnormal uptake in the left adrenal gland. A biopsy was performed showing a metastatic prostatic adenocarcinoma. The patient received systemic treatment, and his prostate-specific antigen level decreased significantly. Our objective is to illustrate an unusual and single site of prostate cancer metastasis, in which precise histological diagnosis was essential for correct clinical management of the patient.

Acute appendicitis is a common surgical emergency in older adults. In the elderly, like in younger cohorts, acute appendicitis most commonly arises without neoplastic underpinnings. However, the occurrence of acute appendicitis in a patient with a concurrent abdominopelvic malignancy should trigger suspicion for the possibility of a metastatic appendiceal neoplasm. We present the case of a 66-year-old man with a background of a biochemically recurrent prostatic adenocarcinoma who presented to the emergency department with acute appendicitis. Histopathologic examination of the resected appendix revealed an unexpected metastatic spread from his prostatic adenocarcinoma.

Muir-Torre syndrome (MTS) is a rare autosomal dominant condition characterized by the presence of at least one cutaneous sebaceous tumor and one visceral malignancy, arising mostly from the gastrointestinal tract. We present the case of a 63-year-old man with several cutaneous and visceral neoplasias in the context of MTS, and a pelvic lymph node lesion diagnosed initially as metastatic sebaceous carcinoma, but later identified as metastasis from a newly diagnosed prostatic adenocarcinoma. Histological similarities between these 2 lesions are discussed. A systematic literature review was conducted evaluating all published cases of patients with MTS in which metastases were reported. Eighteen articles were included in the final synthesis, representing 20 patients with a total of 26 metastases. Seventeen patients (85%) exhibited metastases originating from MTS-related neoplasms, whereas only 2 patients (11%) exhibited metastases from concomitant malignancies. Of the 85% of patients with metastases from MTS-related malignancies, most originated from noncutaneous sources (78% from visceral neoplasms and 22% from sebaceous carcinomas). When stratifying according to metastases, 23 cases (88%) originated from MTS-related lesions, whereas only 3 (12%) originated from unrelated malignancies. Our findings thus demonstrate that most metastases found in MTS patients (88%) do indeed originate from MTS-related neoplasms. Nevertheless, it remains imperative that a broad differential diagnosis is maintained when assessing a novel lesion, to avoid misdiagnoses, as in the present case, with significant therapeutic and prognostic implications.

Background The skeleton represents one of the most common sites to be affected by metastatic tumors. About 65 % of all bone metastases come from the breast cancer in females, and from the prostatic carcinoma in males. A probable diagnostic pitfall may be encountered during the process of decalcification of the bone metastases specimens. This study aimed to evaluate the diagnostic utility of NKX3.1 and HOXB13 and compare them with the traditionally used PSA for the detection of prostatic origin of bone metastases. Material and methods We analyzed 41 tissue specimens of bone metastases originating from prostatic carcinoma. Immunohistochemical staining of NKX3.1, HOXB13 and PSA was done with evaluation of their differential expression. Results NKX3.1, HOXB 13 and PSA were expressed in (41/41), (39/41) and (25/41) respectively of the analyzed cases. On comparing NKX3.1 and HOXB13 positive staining, there was a statistically significant difference (P = 0.000). In addition, the frequency of positive NKX3.1 expression in decalcified bone biopsies of metastatic prostatic adenocarcinoma is statistically higher than that of PSA immunostaining (P = 0.000). We found a statistically significant difference between HOXB13 and PSA positive immunostaining (P = 0.01). Conclusion This study demonstrates that NKX3.1 and HOXB13 are more sensitive markers than PSA for the detection of prostate carcinoma metastatic to the bone following the decalcification process. We recommend use of NKX3.1 and HOXB13, rather than PSA, in the diagnosis of bone metastases originating from prostate cancer.

A 10-year-old entire male French bulldog was presented following clusters of generalized tonic-clonic epileptic seizures. Neurolocalization was consistent with a lesion in the left forebrain. Magnetic resonance imaging of the brain revealed a large, ill-defined, intra-axial, space-occupying lesion at the level of the left temporal and parietal lobes, causing marked compression of the adjacent parenchyma. Computed tomography of the thorax and abdomen was consistent with disseminated metastatic disease. The dog was humanely destroyed and subjected to necropsy examination. Histological examination of the brain revealed a metastasis of prostatic carcinoma within an anaplastic oligodendroglioma in the left forebrain. To the author's knowledge, this is the first report describing clinical, imaging and histopathological features of an intracranial tumour-to-tumour metastasis in the brain of a dog.

Malignant ascites in prostatic acinar adenocarcinoma is very rare. We present an 84-year-old man with a rare malignant ascites due to prostatic adenocarcinoma demonstrating hepatoid differentiation by immunohistochemistry. The patient was diagnosed with the malignant ascites due to metastatic prostatic adenocarcinoma. We identified the unique cytological feature of envelopment of tumour cell clusters by benign mesothelial monolayers.

Bronchoalveolar lavage (BAL) is a useful procedure to evaluate lung infiltrates in order to identify infection, foreign body aspiration, and neoplasms. However, it is indeed unusual to find all three in the same sample. We report such a case in a 68-year-old male with a history of metastatic prostate adenocarcinoma and longstanding chronic obstructive pulmonary disease who presented with features of pneumonia. BAL revealed Aspergillus and parainfluenza infections, food particle aspiration pneumonia, as well as metastatic prostatic adenocarcinoma. The food particles were initially confused for yeast infection, but we finally identified them as nut products. This may be the first documented case of nut product aspiration diagnosed on BAL. The potential pitfalls that may complicate the evaluation are also discussed.

Prostatic ductal adenocarcinoma is an uncommon form of prostatic carcinoma. We report a case of a 63-year-old man who presented with non-infective thrombotic (marantic) endocarditis and an incidental finding of a destructive lesion in the left iliac crest. Core biopsy of the lesion showed a carcinoma with papillary architecture and was initially diagnosed as "metastatic carcinoma of unknown origin". The patient experienced a cerebral infarction and expired six days later. Postmortem examination revealed extensive mixed acinar and ductal adenocarcinoma (Gleason score 5+4=9) in the prostate. Further studies confirmed the bone lesion as metastatic prostatic ductal adenocarcinoma. Although rare, metastatic prostatic adenocarcinoma should be considered in the differential diagnosis in a male patient when the carcinoma shows predominantly papillary architectures. A review of literature is presented to enhance the awareness of this entity.

Nonspecific uptake of prostate-specific membrane antigen (PSMA) on PSMA positron-emission tomography/computed tomography (CT) is normally encountered in benign conditions, which is detected on morphological changes on CT component. However, having a site of uptake without any CT finding is a rare occurrence. We herewith report one such rare case of a 66-year-old male with metastatic prostatic adenocarcinoma, who demonstrated an incidental finding of intense focal PSMA uptake in the lung parenchyma.

The diagnosis of a tumor-to-tumor metastasis in the central nervous system most commonly involves metastasis to a meningioma. These combined lesions are often radiographically unsuspected and mimic a meningioma. Most commonly, the source of metastatic disease are carcinomas from the lung and breast. To our knowledge, fewer than a half dozen cases of metastatic prostatic adenocarcinoma to a meningioma have been documented in the literature. This report documents a 67-year-old man who presented with worsening confusion and altered mental status, accompanied by symptoms of increased urinary frequency, incontinence, and difficulty urinating. Imaging revealed a mass at the base of the bladder and an intracranial lesion, surrounded by edema, which was initially suspicious for intracranial metastasis of prostate cancer. Due to worsening neurological symptoms, the patient underwent craniotomy to remove the intracranial mass. The mass was comprised of a meningothelial meningioma, World Health Organization Grade I, accompanied by atypical epithelioid cells which demonstrated immunoreactivity to prostate specific antigen, chromogranin and neuron specific enolase antibodies, consistent with a metastatic prostatic adenocarcinoma with neuroendocrine differentiation. The patient suffered severe neurological complications post-operatively, developed multiple metastases and expired 12months later. The report reviews current theories as to why meningiomas are the most common host tumor for tumor-to-tumor metastases in the brain and reviews the literature on previously reported cases involving metastatic prostatic adenocarcinoma.

The thyroid gland has a rich vascular supply. However, metastasis to the thyroid is exceedingly rare. The most common tumours that metastasize to the thyroid are breast and lung. The incidence of metastasis is on the rise due to better imaging techniques as well as procedures such as Fine Needle Aspitation Cytology (FNAC) and Immunohistochemistry (IHC). Secondaries from a prostate cancer are most commonly seen in bone, lung and liver. To our knowledge, metastasis from the prostate gland to the thyroid is exceedingly rare. Here, we report a case of metastatic prostatic adenocarcinoma to the thyroid gland two years after prostatectomy.

Context: The diagnosis of prostatic adenocarcinoma on histopathology depends on architectural and cytomorphological features supported by immunohistochemistry (IHC). Though all the prostate markers show excellent specificity, the sensitivity and percentage positivity vary. Aims: In this study, we aim to study the expression of prostein in normal, benign, and malignant (primary and metastatic) lesions with particular emphasis on its utility in the differential diagnosis of poorly differentiated and metastatic prostatic adenocarcinoma along with a standard panel of IHC markers. Settings and Design: This was both a prospective and retrospective as well as descriptive and observational study. Subjects and Methods: All samples from patients with clinically suspected carcinoma prostate from both primary and metastatic sites from June 2015 to May 2016 were included in the study. Samples with difficulty in diagnosis on hematoxylin and eosin staining were subjected to a panel of IHC markers along with prostein. Statistical Analysis Used: Receiver operating curve analysis and Chi-square test. Results: Prostein showed a 100% sensitivity and specificity to identify normal prostatic epithelium, benign and premalignant lesions, and prostatic adenocarcinoma. Prostein showed a specificity of 100% in differentiating prostatic carcinoma from poorly differentiated urothelial carcinoma and in differentiating metastatic prostatic carcinoma from adenocarcinoma of nonprostatic origin. Conclusions: Prostein is a new and promising prostate-specific marker that showed slightly more sensitivity and specificity than prostate-specific antigen. Thus, adding prostein to the IHC panel will greatly improve the detection of poorly differentiated primary and metastatic lesions of the prostate.

Metastatic prostatic adenocarcinoma presenting as a primary lung disease is rare. We present a 52-year-old male with a 3-month history of cough, shortness of breath, and weight loss with clinical and radiological findings suggestive of a primary lung disease: Bilateral interstitial and alveolar opacities with blunting of the costophrenic angles, multiple diffuse foci of consolidations and nodules, predominantly subpleural and located in the lower lobes, and diffuse interlobular septal thickening and peribronchial thickening. The patient underwent bronchoscopy and bronchoalveolar lavage (BAL) was obtained. Cytospin smears were diagnostic for a low-grade adenocarcinoma. Clinically, the patient had elevated serum prostate-specific antigen (PSA) levels greater than 5,000 ng/mL. Because of this, immunocytochemistry for PSA was performed which was positive, confirming the diagnosis of metastatic prostatic adenocarcinoma. This unusual case of metastatic adenocarcinoma of the prostate first diagnosed by BAL highlights the significance of available clinical information and the use of immunocytochemistry for proper diagnosis.

Metastatic carcinoma to the testis is very rare.The incidence of secondary testicular tumors ranges from 0.02 to 2.5% among autopsies ingeneral. Despite the high incidence of prostatic adenocarcinoma and its ability for wide dissemination, metastatic cancer to the testis is a rare phenomenon of prostate carcinoma with only 80 cases reported in the literature.It is diagnosed in autopsies or incidentally, following therapeutic orchiectomies in moreadvanced stages of the disease.Ours is the very first case of prostatic carcinoma metastasizing to the testis, being reported from our country. We are reporting this case because of the rarity of metastasis of prostatic carcinoma to testis and for stressing the need for keeping in mind the possibility of metastatic carcinoma also while dealing with testicular tumors. In our case, unilateral testicular metastasis was detected incidentally after bilateral orchiectomy for hormonal management of metastatic prostatecarcinoma. The metastatic lesion was not identified in physical examination or in macroscopic dissection of the testis after surgery. Microscopy revealed an adenocarcinoma which, given the history of the patient and a positive immunohistochemical stain for PSA, was identified as metastatic prostatic adenocarcinoma.Journal of Pathology of Nepal (2015) Vol. 5, 784-786

While cutaneous metastases are already extremely rare in primary metastatic prostatic adenocarcinoma, cutaneous manifestations in recurrent prostate cancer have rarely been described prior to this report. Here we present the case report of a 93-year-old male who underwent radical prostatectomy but eventually suffered from a previously undescribed recurrence of prostatic adenocarcinoma with distant cutaneous metastases to proximal right lower leg.

BACKGROUND: Conflicting roles for Slit2, a protein involved in mediating the processes of cell migration and chemotactic response, have been previously described in prostate cancer. Here we use immunohistochemistry to evaluate the expression of Slit2 in normal donor prostate (NDP), benign prostatic hyperplasia (BPH), high-grade prostatic intraepithelial neoplasia (HGPIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets). METHODS: Tissue microarrays were immunostained for Slit2. The staining intensities were quantified using automated image analysis software. The data was statistically analyzed using one-way analysis of variance with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Eleven cases of NDP, 35 cases of NAC, 15 cases of BPH, 35 cases of HGPIN, 106 cases of PCa, and 37 cases of Mets were analyzed. RESULTS: Specimens of PCa and HGPIN had the highest absolute staining for Slit2. Significant differences were seen between PCa and NDP (P < .05), PCa and NAC (P < .05), HGPIN and NDP (P < .05), and HGPIN and NAC (P < .05). Whereas the average Mets staining was not significantly different from NDP or NAC, several individual Mets cases featured intense staining. CONCLUSIONS: To our knowledge, this represents the first study comparing the immunohistochemical profiles of Slit2 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC. These findings suggest that Slit2 expression can be increased in HGPIN, PCa, and Mets, making it a potentially important biomarker for prostate cancer.

With the exception of skin cancer, prostatic adenocarcinoma represents the most common cancer among men in the United States and the second most common cause of cancer mortality. Mortality is often associated with metastatic disease, which in the case of prostatic adenocarcinoma typically involves bones and only rarely affects the skin. Although clinical history and examination, laboratory tests and routine pathology can suggest the prostate as a source of metastatic disease, immunohistochemistry – specifically, for prostate-specific antigen (PSA) – is often used to help establish the diagnosis. We report a case of cutaneous metastatic prostatic adenocarcinoma presenting in the inguinal region of a 78-year-old man 5 years after his initial diagnosis. The case is unusual in that the clinical appearance mimicked a vascular proliferation and in that the metastatic prostatic adenocarcinoma failed to express PSA. Rather, expression of prostatic acid phosphatase was observed. Rattanasirivilai A, Kurban A, Lenzy YM, Yaar R. Cutaneous metastasis of prostatic adenocarcinoma: a cautionary tale.

α-Methylacyl-coenzyme A racemase (AMACR) is a sensitive and specific tissue marker for the diagnosis of prostatic carcinoma. However, limited data are available on AMACR expression in residual prostatic carcinoma following hormone therapy. We analyzed 64 residual or recurrent prostatic adenocarcinomas following hormonal therapy for the expression of AMACR using a monoclonal antibody (P504S) to AMACR. In 20 localized cases, AMACR staining was absent in 11 (55%), 1+ in 6 (30%), and 2+ or 3+ in 3 (15%). However, in 15 metastatic cases, AMACR was absent in 1 (7%), 1+ in 3 (20%), and 2+ or 3+ in 11 (73%). None of the 29 postradiotherapy cases showed complete absence of AMACR staining: 2 (7%) were 1+, and 27 (93%) were 2+ or 3+. AMACR expression was reduced significantly in the majority of posthormonal residual carcinomas, whereas in postradiotherapy and in hormone-refractory metastatic prostatic adenocarcinoma, AMACR expression was retained. Therefore, the diagnosis of residual prostatic carcinoma after hormonal therapy using AMACR immunostaining must be interpreted with caution. Furthermore, AMACR might have a role in the recurrence of prostatic adenocarcinoma after medical therapy.

Metastatic prostatic adenocarcinoma to the orbit diagnosed by prostate-specific antigen staining

We combined laser-assisted microdissection from HE-stained paraffin sections, degenerated oligonucleotide-primed polymerase chain reaction (DOP-PCR), and comparative genomic hybridization (CGH) to analyse chromosomal imbalances in small tumour areas consisting of 50-100 cells. This approach was used to investigate intratumour genetic heterogeneity in a case of metastatic prostatic adenocarcinoma and chromosomal changes in areas of prostatic intraepithelial neoplasia (PIN) adjacent to the invasive tumour. In four microdissected invasive tumour areas with different histological patterns (acinar, cribriform, papillary and solid) marked intratumour heterogeneity was found by CGH. Recurrent chromosomal imbalances detected in at least two microdissected tumour areas were gains on 1p32--p36, 2p22, 3q21, 7, 8q21--q24, 11q12--q13, 16p12--p13, 17, 19 and loss on 16q23. Additional chromosomal changes were found in only one of the microdissected areas (gains on 16q21--q23, 20q22 and losses on 8p21--p23, 12p11--q12, 12q21--q26, 13q21--q34, 16q12, and 18q22). In PIN, gains on chromosomes 8q21--q24 and 17 were found in both samples investigated (low and high grade PIN), while gains on chromosomes 7, 11q, 12q, 16p, and 20q and losses on 2p, 8p21--p23, 12q were found only in one PIN area. Controls to ensure reliable CGH results consisted in CGH analyses of (i) approximately 80 microdissected normal epithelial cells, which showed no aberrations after DOP-PCR and (ii) larger cell numbers (approximately 10(5) or 10(7) cells) of the primary tumour investigated without DOP-PCR and partially displaying the chromosomal imbalances (gain on 16p12--p13, losses on 2p25, 8p21--p23, 12p11--p12, 12q21--q26, 18q22) found in the small microdissected areas. Microsatellite and FISH analyses further confirmed our CGH results from microdissected cells. The combined approach of laser-assisted microdissection, DOP-PCR and CGH is suitable to identify early genetic changes in PIN and chromosomal imbalances associated with the particular histological patterns of invasive prostatic adenocarcinoma.

Prostate cancer metastasis to bone and lymph nodes is common, but metastasis to the gallbladder is rare. We report a case of a 72 year-old-male with a three month history of weight loss and nausea. On further evaluation he was found to have an elevated alkaline phosphatase and radiographic evidence of prostate cancer, skeletal metastases, and a gallbladder mass concerning for concomitant gallbladder carcinoma. Prostate biopsy confirmed high-grade prostatic adenocarcinoma. The patient underwent laparoscopic cholecystectomy and pathologic evaluation of the gallbladder revealed metastatic prostatic adenocarcinoma without evidence of gallbladder carcinoma. This case demonstrates a possible association between prostatic adenocarcinoma and the gallbladder.

Renal metastasis from prostatic origin is an uncommon event. Advanced prostate cancer locally invades the seminal vesicles, bladder and regional lymph nodes. Other metastatic sites are the lung, bone and other visceral organs. We present a 55-year old, Hausa man from Northern Nigeria who was managed as a case of infected renal cyst which later turned out to be a metastatic prostatic adenocarcinoma with a rare pattern of widespread bony metastases.Renal metastasis from prostate adenocarcinoma is a rare occurrence, however, high level of suspicion is needed in order to avoid potential diagnostic pitfall.

Objective Prostate specific membrane antigen (PSMA) is primarily expressed in glandular prostatic tissue and is frequently utilized to detect primary or metastatic prostatic adenocarcinoma (CaP). A purported novel application of PSMA detection is the intraoperative real-time identification of CaP using radioimmunoscintigraphy to define the extension of the surgical resection. Considering that PSMA expression has been reported in other tissues, we evaluated its immunoexpression in prostatic neurovascular bundle elements to assess the convenience and safety of the aforementioned procedure. Materials and methods Twenty consecutive specimens of radical prostatectomy (RP) were retrieved from our surgical pathology archives. PSMA immunoexpression (Clone 3E6, DAKO) was assessed in a representative section from each specimen containing neurovascular bundle elements. Results PSMA expression was documented in 20/20 of examined CaP slides. Most cases exhibited an apical/cytoplasmic or cytoplasmic with membranous accentuation pattern of staining. Focal weak to moderate cytoplasmic staining was detected in associated ganglionic tissue in 3/15 of the examined RP. In all cases, staining was cytoplasmic, less extensive, and weaker than the pattern observed in CaP. None of the peripheral nerve sheath cells or lymphovascular components of the examined neurovascular bundles were positive for PSMA. Conclusions We found focal positive PSMA expression in the ganglionic cells of the prostatic neurovascular bundle. Our results suggest that the radioimmunoscintigraphic detection of radiolabeled PSMA antibodies might not be entirely specific for prostatic cells; this observation must be taken into account should an intraoperative PSMA-based fluorescent imaging technique be used to define the extension of the surgical procedure.

We report the case of a 78-year-old man who developed a breast mass 12 months after hormonal therapy for palliation of prostatic adenocarcinoma. On histologic and immunohistochemical examination, the breast tumor revealed a unique collision tumor composed of metastatic prostatic adenocarcinoma and solid papillary breast carcinoma.

NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. Although most studies have shown that staining for NKX3.1 protein is positive in the majority of primary prostatic adenocarcinomas, it has been shown to be downregulated in many high-grade prostate cancers, and completely lost in the majority of metastatic prostate cancers (eg, in 65% to 78% of lesions). A recent study showed that NKX3.1 staining with a novel antibody was highly sensitive and specific for high-grade prostatic adenocarcinoma when compared with high-grade urothelial carcinoma. This raised the question that this antibody may perform better than earlier used antibodies in metastatic prostate tumors. However, the sensitivity and specificity for prostate carcinomas for this antibody in metastatic lesions was not determined. Although prostate-specific antigen (PSA) and prostatic-specific acid phosphatase (PSAP) are excellent tissue markers of prostate cancer, at times they may be expressed at low levels, focally, or not at all in poorly differentiated primary and metastatic prostatic adenocarcinomas. The purpose of this study was to determine the performance of NKX3.1 as a marker of metastatic adenocarcinoma of prostatic origin. Immunohistochemical staining against NKX3.1, PSA, and PSAP was carried out on a tissue microarray (TMA) (0.6-mm tissue cores) of hormone naive metastatic prostate adenocarcinoma specimens from lymph nodes, bone, and soft tissue. To determine the specificity of NKX3.1 for prostatic adenocarcinoma, we used TMAs that contained cancers from various sites including the urinary bladder, breast, colon, salivary gland, stomach, pancreas, thyroid, and central nervous system, and standard paraffin sections of cancers from other sites including the adrenal cortex, kidney, liver, lung, and testis. Overall 349 nonprostatic tumors were evaluated. Any nuclear staining for NKX3.1 was considered positive and the percentage of cells with nuclear staining and their mean intensity level were assessed visually. Sensitivity was calculated by considering a case positive if any TMA core was positive. The sensitivity for identifying metastatic prostatic adenocarcinomas overall was 98.6% (68/69 cases positive) for NKX3.1, 94.2% (65/69 cores positive) for PSA, and 98.6% (68/69 cores positive) for PSAP. The specificity of NKX3.1 was 99.7% (1/349 nonprostatic tumors positive). The sole positive nonprostatic cancer case was an invasive lobular carcinoma of the breast. NKX3.1 seems to be a highly sensitive and specific tissue marker of metastatic prostatic adenocarcinoma. In the appropriate clinical setting, the addition of IHC staining for NKX3.1, along with other prostate-restricted markers, may prove to be a valuable adjunct to definitively determine prostatic origin in poorly differentiated metastatic carcinomas.

Prostate adenocarcinoma can manifest as a fairly indolent tumor or as a very aggressive cancer with significant invasive and metastatic potential. Common metastatic sites include bone, liver, lymph nodes, and adrenal glands. Dermatologic manifestations are rare. We present a case of a man who presented with breast skin changes that mimicked inflammatory breast carcinoma with specialized testing ultimately giving a diagnosis of metastatic prostatic adenocarcinoma. A 78-year-old man presented with left breast redness and swelling. Examination revealed an erythematous rash with subcutaneous edema over the left hemithoracic area. A breast ultrasound showed no focal mass, and a breast core biopsy had no evidence of tumor. A skin biopsy showed metastatic carcinoma in dermal lymphatics, and the tumor was found to have no estrogen or progesterone receptors or HER2 expression. Computed tomography scans, positron emission tomography, and a nuclear bone scan revealed widespread skeletal metastases. The patient received a 3-month course of capecitabine and cyclophosphamide with no improvement in his skin lesions. Subsequent immunohistochemical staining on the tumor specimen was positive for prostate-specific antigen (PSA) and alpha-methyl-CoA-racemase, confirming a diagnosis of metastatic prostatic adenocarcinoma. He received leuprolide and bicalutamide and demonstrated significant improvement with near-complete resolution of his skin lesions and a decrease in his PSA level. Prostatic adenocarcinoma presenting initially as a breast malignancy is a rarely recognizable clinical event. Undoubtedly, increased awareness and recognition of the rare entity described herein will allow for the prompt initiation of specific therapies, which might be of benefit to many patients.

There are important interactions between prostatic tumours and bone. This study was designed to examine whether prostatic tissue can express bone inductive factors, in particular, the Bone Morphogenetic Proteins (BMPs). The polymerase chain reaction (PCR) has been used to screen for the expression of BMPs one to six in the prostatic tissue of patients with benign prostatic hyperplasia (BPH), non-metastatic prostatic adenocarcinoma and metastatic prostatic adenocarcinoma. BMPs were expressed in both benign and malignant prostate tissue and in the prostate tumour cell lines, PC3 and DU145. BMPs were also expressed in ocular melanoma tissue, a tissue which rarely metastasizes to bone. BMP-6 expression was detected in the prostate tissue of over 50% of patients with clinically defined metastatic prostate adenocarcinoma, but was not detected in non-metastatic or benign prostate samples or in ocular melanoma tissue. These findings suggest that the BMPs may play a role in the osteoinductive activity of prostate metastases and that the pattern of expression of BMPs may be important in the pathogenesis of osteoblastic metastases associated with prostate adenocarcinoma. Images Figure 1

Introduction: Prostate cancer has a high tendency to spread to bone. Pulmonary metastasis and generalized lymphadenopathy commonly develop after pelvic and bone involvement have already occurred. Few patients with prostate cancer present initially with symptomatic metastatic lung lesions and lymphadenopathy without any other concomitant distant dissemination. Case presentation: We report a case of a 73-year-old white male who sought medical help for symptoms of cough, hemoptysis, and dyspnea. A chest X-ray was done revealing multiple "cannon ball" infiltrates involving all segments of the lung parenchyma. Fine-needle aspiration cytology under computed tomography guidance of a subpleural lesion revealed adenocarcinomatous cells. Despite the absence of any detectable osseous lesions and with the presence of multiple hilar, mediastinal, para-aortic, and pelvic lymphadenopathy, the patient had a complete work-up in search for the primary adenocarcinoma. His prostate specific antigen was 146 ng/ml and a prostatic biopsy done, revealing an acinar prostatic adenocarcinoma. A tru-cut biopsy of a lung lesion under computed tomography guidance showed a metastatic prostatic adenocarcinoma positive for prostate specific antigen stain. Conclusion: This case sheds light on an unusual metastatic pattern of prostatic adenocarcinoma. It also emphasizes the importance of including prostate cancer in the differential diagnosis of men with adenocarcinoma of unknown origin.

Carcinoma of the prostate is predominantly a disease of older men. Men younger than 50 years of age account for approximately 1% of all patients diagnosed with prostate cancer. Patients generally present with urinary symptoms and rarely with metastatic disease. Lymphatic spread typically occurs to the obturator and internal iliac nodes. We report a case of an aggressive prostate adenocarcinoma in a 47-year-old white male who presented with nausea, vomiting, and enlarged inguinal lymph nodes for 1 month. A fine needle aspiration biopsy (FNAB) and immunohistochemical stains performed on the FNAB revealed metastatic prostatic adenocarcinoma. The initial clinical presentation of inguinal lymphadenopathy, the age of the patient and the cytologic features made this an unusual case.

We present a case of a patient who was initially diagnosed with poorly differentiated prostatic adenocarcinoma on prostate needle core biopsy. Upon staging workup, a computed tomographic scan showed a 9-cm left renal mass involving mainly the pelvicalyceal system. Positron emission tomographic scan showed increased uptake in para-aortic, paracaval, and retrocaval lymph nodes suspicious for metastatic disease. Left nephrectomy revealed involvement with extranodal Rosai-Dorfman disease. Lymphadenectomy revealed metastatic prostatic adenocarcinoma; however, the lymph nodes did not show evidence of Rosai-Dorfman disease. Isolated involvement of the kidney by Rosai-Dorfman disease is very rare. The combination of prostatic adenocarcinoma and isolated extranodal Rosai-Dorfman disease of the kidney makes this case unique.

Metastasis from prostate to thyroid gland is very uncommon. Here we report a 77-year-old man who was admitted to the hospital because of a nodular goiter. A fine-needle aspiration biopsy of the nodule showed metastatic prostatic adenocarcinoma. This is the second case of a metastatic prostate carcinoma to the thyroid gland.

We undertook a detailed histologic study to identify specific morphologic features that may aid in distinguishing prostatic adenocarcinoma with lung metastases (PALM) from other pulmonary tumors with similar histologic features. In 16 cases, we found 3 predominant architectural patterns: microacinar (n = 10), tubulopapillary (ductal; n = 4), and carcinoid-like (n = 2). Characteristic features of PALM included small acinar and/or cribriform growth, frequent lymphangitic permeation, lack of stromal response, uniform round nuclei with prominent nucleoli, intraluminal blue mucin, and prominent cell borders. By immunohistochemical staining, prostate-specific antigen and prostate-specific acid phosphatase were present in 13 of 14 and 13 of 13 cases, respectively. Metastatic prostatic duct adenocarcinoma exhibited morphologic features similar to metastatic colonic adenocarcinoma. Two cases had a carcinoid-like appearance with nested or solid architecture, parachromatin clearing, and prominent nucleoli, but lacked the finely stippled chromatin pattern of carcinoid tumors. Several features that may result in misinterpretation or lack of association of the neoplasm in the lung with a prostatic primary include lung metastasis preceding the detection of a prostatic primary tumor, solitary pulmonary nodule, tubulopapillary (ductal) or carcinoid-like pattern, scant material in which histologic features of metastatic prostate carcinoma are not fully appreciated, and frequent necrosis. Attention to specific discriminating histologic features, supported by immunohistochemical staining, may be useful in the differential diagnosis, which is therapeutically and prognostically critical.

Background Fine-needle biopsy (FNB) diagnosis of metastatic carcinoma is based on cytological evaluation and ancillary investigations, e.g., immunocytochemistry. We present three cases which illustrate the utility of biochemical assay for tumour-specific markers as an aid to cytological diagnosis. Methods/Results Case 1 was a 68-year-old man with previously resected prostatic adenocarcinoma who presented with a neck mass. FNB yielded necrotic debris with scant viable atypical cells. The Hanks solution into which drops of FNB material had been deposited was centrifuged for cell block preparations, and biochemical assay for PSA on the fluid supernatant yielded a result of 7.9 μg/L. The elevated PSA was suggestive of metastatic prostatic adenocarcinoma, and this interpretation was confirmed histologically. Case 2 was a 30-year-old man with a past history of thyroidectomy for papillary thyroid carcinoma (PTC) who presented with two neck masses. FNB showed abnormal epithelial cells with features suggestive of PTC. Assay for thyroglobulin on Hanks solution supernatant yielded a value of 1163 μg/L (serum thyroglobulin 1.3 μg/L). This supported a diagnosis of metastatic PTC, which was subsequently confirmed in a histological specimen. Case 3 was a previously well 36-year-old man who presented with masses in the thyroid and neck lymph nodes. FNB showed a few atypical cells and amorphous extracellular material. Calcitonin level on the FNB supernatant (993 pg/mL) and serum calcitonin (1818 pg/mL) were elevated. A diagnosis of medullary thyroid carcinoma was made, and confirmed histologically. Conclusions Biochemical assay for tumour markers is a useful ancillary technique for assisting in FNB diagnosis of metastatic carcinoma, particularly when morphological assessment is compromised by low cellularity or cellular degeneration.

Background: Interleukin-6 (IL-6) is a pleiotropic cytokine that elicits multiple physiological processes including immune responses, hematopoiesis, and cellular proliferation and differentiation. IL-6 has also been implicated in a number of pathophysiologic processes, including carcinogenesis. Multiple studies suggest that IL-6 may contribute to the development and/or progression of prostate cancer, and high systemic levels of IL-6 are associated with a more aggressive clinical course. A number of studies have indicated that prostatic adenocarcinoma cells express IL-6; yet, the source of IL-6 production in the prostate tumor microenvironment is debatable and it remains unclear if the cytokine acts in an autocrine or paracrine manner. Understanding the cellular origin of IL-6 is essential to establishing the mechanistic basis by which IL-6 may promote prostate cancer progression. Methods: Quantitative PCR (qPCR) and chromogenic in situ hybridization (CISH) were used to study IL-6 expression in primary clinical prostatic carcinomas. As an initial approach, RNA derived from 11 prostate cell lines and 10 matched benign and tumor frozen prostate tissue samples were analyzed for IL-6 expression by qPCR. Next, formalin-fixed, paraffin embedded (FFPE) samples from the 11 cell lines, 21 prostatectomy samples, and 12 metastatic prostate cancer biopsy or autopsy tissue samples were analyzed by chromogenic in situ hybridization (CISH) for IL-6 mRNA (RNAscope, Advanced Cell Diagnostics, Inc.). Results: Three of the prostate cell lines (PrSC, RWPE, DU145) were found to be positive for IL-6 expression by both qPCR and CISH, indicating complete concordance between the two assays. Surprisingly, qPCR analyses revealed that benign prostate tissues most often had higher expression of IL-6 than matched tumor. Subsequent IL-6 CISH analysis indicated that prostate adenocarcinoma cells do not express IL-6 mRNA in either primary or metastatic cancer cells; rather, IL-6 mRNA expression was nearly exclusively restricted to the prostate stromal compartment and was highly up-regulated in areas of acute inflammation and prostatic atrophy. Conclusions: Our results are in contrast to published literature that argues that prostate cancer cells are the origin of IL-6 in the prostate tumor microenvironment and that prostate cancer progression is mediated by autocrine IL-6 signaling. The restriction of IL-6 expressing cells primarily to the prostate stromal compartment may alter the current understanding of how IL-6 may mediate the development and progression of prostate cancer. Citation Format: Shu-Han Yu, Qizhi Zheng, Jun Luo, Anne Macgregor-Das, Emmanuel S. Antonarakis, Angelo M. De Marzo, Karen Sfanos. Interleukin-6 expression is restricted to the prostate stromal compartment and is not expressed by either primary or metastatic prostatic adenocarcinoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1648. doi:10.1158/1538-7445.AM2014-1648

INTRODUCTION: Tumour to tumour metastatis is an unusual but well recognized phenomenon. We present a rare case of a metastatic prostatic adenocarcinoma into a meningioma. METHOD: A 58 year old right handed gentleman was referred to our neuro-oncology service. He reported a history of progressive headache spanning several months but only sought medical attention when he developed focal upper limb seizures and episodic speech arrest. Computed tomography (CT) revealed a left parafalcine lesion. He was started on dexamethasone and went on to have a magnetic resonance imaging (MRI) brain and staging CT. This confirmed disseminated lymphadenopathy and supraclavicular lymph node biopsy diagnosed metastatic prostatic adenocarcinoma, which correlated with elevated prostate specific antigen (PSA). He was started on Degarelix. Pre operative MRI showed a significant reduction in the size of the lesion. This may be due to response to Degarelix or dexamethasone or both. RESULTS: Histology revealed two different populations, an atypical component of small cells positive for PSA, PSAP, CKAE1/AE3 and negative for EMA, vimentin and progesterone receptor thus consistent with a metastatic prostatic adenocarcinoma. Additionally, there were uniform cells with oval and bland nuclei. This component was positive for EMA, vimentin, progesterone receptor and CD56 and negative for CKAE1/AE3 and prostatic markers, consistent with a WHO grade 1 meningothelial meningioma. CONCLUSION: We present a rare phenomenon of metastatic prostatic carcinoma into a meningioma. Interestingly, the tumour showed a marked reduction in size on pre-operative imaging. This is likely due to a response of the metastatic component to anti androgen and steroid therapy.

Summary Case A 57 year-old-man presented with a maxillary tumor which proved to be an adenocarcinoma. The prostate was hard and PSA were high. Biopsy confirmed the diagnosis of metastatic prostatic adenocarcinoma. Evolution was fatal despite a medico-surgical treatment. Discussion Facial bone metastases are rare comparatively to the high metastatic incidence in the rest of the skeleton.

Metastatic carcinoma to the testis is very rare. Metastasis of prostate adenocarcinoma to testis was detected incidentally after bilateral orchiectomy for hormonal management of metastatic prostate carcinoma. The metastatic lesion was not identified in physical examination or in macroscopic dissection of the testis after surgery. Microscopy revealed an adenocarcinoma which, given the history of the patient and a positive immunohistochemical stain for PSA, was identified as metastatic prostatic adenocarcinoma.

Purpose: Histological changes in lymph nodes simulating metastatic prostatic adenocarcinoma are reported.Materials and Methods: Lymph node frozen sections from 3 patients with prostatic cancer displayed marked histiocytosis. This tissue was subjected to histochemical, immunohistochemical and electron microscopic studies.Results: Only 1 erroneous diagnosis of metastasis was made. All patients had hip prostheses for at least 6 years. Tissue replacing up to 80 percent of lymph nodes consisted of histiocytes containing large amounts of polyethylene.Conclusions: Hip replacement predisposes the patient to have pelvic lymph node histiocytosis mimicking metastatic adenocarcinoma. This history should be communicated to the pathologist. Polyethylene is the most important factor in the cause of post-prosthesis lymph node histiocytosis.

Background: Invasive breast carcinoma is one of the most common cancers of women. Parameters such as lymph node status, tumor grade, and the status of hormone receptors are among the main prognostic determinants of this cancer. Immunohistochemical detection of prostate-specific antigen (PSA) is widely used to identify metastatic prostatic adenocarcinoma. However, its immunoreactivity has been found in some non-prostatic tissues. This study was conducted to assess PSA expression in invasive breast carcinoma and its relationship with routine clinicopathologic parameters. Materials and Methods: 100 formalin-fixed and paraffin-embedded invasive breast carcinoma tissue specimens from the pathology archive of Alzahra hospital (Isfahan, Iran) were studied for the expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and PSA by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing PSA staining. The relationship between PSA expression and other markers, age, lymph node status, tumor subtype, and tumor grade was then studied. Results: No association was found between PSA expression on one hand and PR, Her2/neu, age, lymph node status, tumor grade, and tumor subtype on the other. PSA score was reversely correlated with ER expression ( P = 0.015). Conclusion: Despite the reverse relationship between PSA expression and the immunoreactivity of ER, PSA expression was not correlated with other prognostic factors. Therefore, the detection of PSA by immunohistochemistry does not seem to be a significant prognostic parameter in patients with invasive breast carcinoma.

Neuroendocrine differentiation of prostatic adenocarcinoma has received considerable attention in recent years. The objectives of this study were to characterize the incidence, pattern of distribution and peptide hormone immunoreactivities of neuroendocrine differentiated tumor cells in prostatic carcinoma metastases; determine the correlation of neuroendocrine differentiation and deoxyribonucleic acid content in lymph node metastases, and determine the prognostic role of neuroendocrine differentiation of metastases in stage D1 cancer. We examined immunohistochemically 62 metastatic lesions (41 pelvic lymph nodes and 21 bone metastases) for the presence of chromogranin-A expressing tumor cells. Of 41 lymph nodes and 21 bone metastases 19 (46%) and 11 (52%), respectively, contained chromogranin-A immunoreactive cells. These cells were commonly found to comprise the minority of tumor cells in the metastases and typically were distributed in a dispersed pattern. Serotonin and peptide hormone immunocytochemistry in 19 cases (12 lymph nodes and 7 bone metastases) demonstrated neuroendocrine cells containing thyroid-stimulating hormone and serotonin in 17 (89%) and 10 (53%), respectively. All 7 bone metastases contained thyroid-stimulating hormone immunoreactive cells. The presence of chromogranin-A positive cells did not correlate statistically with deoxyribonucleic acid content of lymph node metastases nor with disease specific survival in patients with stage D1 prostate cancer. Our results indicate that a substantial proportion of prostate cancer metastases contain a subpopulation of cells expressing a neuroendocrine phenotype similar to primary tumors. These cells are capable of elaborating certain biogenic amines and peptide hormones. However, in stage D1 prostate cancer nodal lesions expressing neuroendocrine differentiation do not appear to have significant prognostic value.

The authors report a case of metastatic prostate cancer masquerading as a primary lung tumor. Histologically, the lung tumor displayed eosinophilic crystalloids in the malignant glands typical of those previously described in prostatic adenocarcinoma. Review of histologic material from 30 additional patients with metastatic prostate cancer failed to reveal crystalloids in the metastases. Seven patients with histologic material from locally advanced prostatic adenocarcinoma, defined as spread to the rectum, bladder, or nonnodal pelvic soft tissue, were also reviewed. One of these patients demonstrated crystalloids in the bladder extension of locally advanced prostatic adenocarcinoma. Although rare, the presence of crystalloids may be used as strong evidence for the prostatic origin of an adenocarcinoma of uncertain origin.

Metastatic carcinoma involving the external auditory canal is a very uncommon condition. Twenty-five cases have been reported. The most common cancer to metastasize through the blood stream to the external canal is breast carcinoma (25%), followed by lung (19%), kidney (11%), stomach (6.4%), bronchus (5.7%), and prostate (5.7%).1 These patients are typically asymptomatic. The majority of reported cases indicate that otologic symptoms usually arise late in the course of the disease. This article reports a clinical case of a 60-year-old man seen with otalgia, hearing loss, and disequilibrium resulting from metastases to the temporal bone from prostate carcinoma.

Metastasis to the temporal bone is uncommon. In some cases, metastasis may be the first evidence of malignant dissemination, but more frequently, the diagnosis is unsuspected, possibly because ear symptoms are overshadowed by those deriving from the primary tumor. It is not until they have symptoms like hearing loss, otalgia, facial nerve paralysis, periauricular swelling, otorrhea, or even an aural mass that patients usually undergo treatment at the late stage of the disease course. Tumors of the breast, lung, and kidney are the most common sources of temporal bone metastasis. Although axial bone and cranial metastases are common in patients with prostatic carcinoma, temporal bone involvement is extremely rare. We report a case of metastatic prostatic adenocarcinoma in the temporal bone which was diagnosed with delay.

A peripheral blood smear from a patient with probable splenic lymphoma with villous lymphocytes (SLVL) showed clumping of lymphoma cells. The clumping was not seen in films made from unanticoagulated blood, and has not been previously described in lymphomas. The patient also had metastatic prostatic adenocarcinoma for 30 months before lymphoma was diagnosed and the clumped cells posed diagnostic problems.

Since the introduction of hormonal therapy for the treatment of metastatic prostatic adenocarcinoma, there have been 33 reports of metastases of prostate carcinoma to the breast. We report two cases of diethylstilbestrol (DES)-treated patients with metastatic prostate adenocarcinoma who developed breast masses. The lesions had infiltrative patterns simulating primary breast carcinoma. Immunoperoxidase stains, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) were positive, identifying these cases as metastatic prostatic carcinoma to the breast. Differentiating primary from secondary tumors in these patients is difficult since there have been 10 reports of primary breast carcinoma occurring in DES-treated patients with prostatic adenocarcinoma. Their differentiation is important to direct appropriate therapy, and PSA and PAP immunoperoxidase stains are important in their correct classification.

Adenocarcinoma of the prostate is the most common visceral malignancy in men and has a tendency to metastasize to the axial skeleton, lungs, adrenal, and liver. Cutaneous metastasis is extremely rare and portends resistance to therapy and poor prognosis. We report an unusual case of metastatic prostatic adenocarcinoma to the penile skin. A 77-year-old man presented with two-month history of a subcutaneous nodule on the dorsal aspect of the glans penis in the region of the coronal ridge. The patient was seven years status-post radical prostatectomy for adenocarcinoma of the prostate, and had previously received both radiation and hormonal therapy for metastatic bone disease. The penile nodule was excised and microscopic examination showed infilteration of the dermis by malignant acini exhibiting a cribriform growth pattern and central comedonecrosis. Immunohistochemical staining revealed that the tumor cells were negative for prostate specific antigen (PSA), thyroid transription factor-1, cytokeratin 7, and cytokeratin 20, but were strongly and diffusely positive for prostatic acid phosphatase (PAP). Based on these findings, a diagnosis of metastatic prostatic adenocarcinoma was established. In addition to the unusual location on the penis, this case also demonstrates the importance of immunostaining for PAP when metastatic prostatic adenocarcinoma is suspected.

Pseudohyperplastic prostatic adenocarcinoma is a rare histologic variant of prostatic adenocarcinoma that resembles benign nodular hyperplasia. Immunohistochemistry can verify the absence of basal cells, but it is frequently admixed with conventional adenocarcinoma. Because fine needle aspiration cytology is rarely performed in primary prostatic adenocarcinoma, the cytology of the pseudohyperplastic variant has not been described. We experienced a case of metastatic pseudohyperplastic adenocarcinoma in a pulmonary nodule of 75-year-old man. The cytologic smear was mostly composed of large, flat sheets with elongated branching papillae in a clean background. The sheets showed a well-defined honeycomb appearance of tall columnar, regularly arranged monotonous cells with little cytologic atypia. In subsequent prostatic biopsy, pseudohyperplastic variants were identified together with conventional adenocarcinoma of Gleason's grade 3 and 4. The cytologic features of pulmonary nodules were identical to those of pseudohyperplastic components of prostatic adenocarcinoma.