Case Report
Primary Adenosquamous Carcinoma of the Prostate: A Rare Aggressive Tumor Shwetank Mishra, Hemant Goel, Nipun Awasthi, Anurag Puri, Rajkumar Mahapatra, D.K. PAL Clinical Practice Points Primary adenosquamous cell carcinoma (ASC) of the
prostate is a very rare and aggressive form of prostate cancer, making up < 1% of all diagnoses. Since its initial description by Thompson in 1942, there have been fewer than 30 cases reported in the literature. Recent reports of age-adjusted incidence rates of ASC have been shown to be about 0.03 cases per million per year making it less prevalent than pure squamous cell carcinoma, an exceedingly rare subtype in itself. The histogenesis of this tumor remains uncertain. The stimulus for the development of the squamous metaplastic cells had been thought to be related to hormone therapy or radiation therapy, or both.
However, we report a case of ASC arising spontaneously in a 60-year-old man with no previous history of risk of exposure. A close scrutiny shows that 4 of the 12 well-established cases lack a history of such therapy. In primary ASC of the prostate, the prostate-specific antigen PSA level is usually within normal range, so digital rectal examination and a high index of suspicion become part and parcel of diagnosing such rare carcinomas, as was found in this case. In addition to this diagnostic dilemma, urologists also find it difficult to manage such cases owing to lack of a definite treatment protocol resulting from the rarity of such tumors.
Clinical Genitourinary Cancer, Vol. 12, No. 1, e29-31 ª 2014 Elsevier Inc. All rights reserved. Keywords: Adenosquamous, Carcinoma, Prostate
Introduction Primary adenosquamous cell carcinoma (ASC) of the prostate is a very rare and aggressive form of prostate cancer. Since its initial description by Thompson in 1942, fewer than 30 cases had been reported in the literature.1 Although the majority of these cases arise subsequent to hormonal or radiation treatment with squamous differentiation, approximately one third of cases arise in a de novo setting.2-4 We report a case of ASC arising spontaneously in a 60year-old man with no previous risk factors.
Case Report A 60-year-old man presented with chief complaints of irritative/ storage lower urinary tract symptoms, low back pain, and 2 episodes of hematuria. He had no voiding lower urinary tract symptoms, Department of Urology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India Submitted: Mar 25, 2013; Revised: Aug 8, 2013; Accepted: Aug 27, 2013; Epub: Oct 19, 2013 Address for correspondence: Shwetank Mishra, MS, Department of Urology, Institute of Post Graduate Medical Education and Research, Kolkata-700020, West Bengal, India E-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2013.08.006
dysuria, graveluria, or history of urinary retention. There was no significant medical or family history. On digital rectal examination, the prostate was enlarged and nontender, with no discernible nodules but a hard consistency. The serum PSA level was 2.14 ng/ mL. On a transrectal ultrasonographically guided prostate biopsy sample, moderately differentiated ASC of the prostate with perineural invasion was revealed. About 65% of the prostatic tissue present in the biopsy sample was involved (Fig. 1). A contrastenhanced computed tomographic scan of the abdomen and pelvis showed a grossly enlarged prostate with heterogeneous enhancement and invading rectum, seminal vesicles, and urinary bladder (Fig. 2). A bone scan revealed multiple osteolytic bone lesions with increased vascularity favoring a neoplastic cause (Fig. 3). Liver function test results and chest radiography were normal. Because of the extensive metastatic nature of the disease along with bone pain, androgen deprivation therapy was started. We followed the patient with PSA values every 3 months, but they remained < 4 ng/mL. The patient died 9 months after confirmation of the diagnosis.
Discussion ASC of the prostate is 1 of the rarest and most aggressive subtypes of prostate cancer.5 Recent reports of age-adjusted incidence rates of
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Primary Adenosquamous Carcinoma of the Prostate Figure 1 Histopathologic Slide Showing Both Adenomatous and Squamous Elements
ASC have been shown to be about 0.03 cases per million individuals per year, making it less prevalent than pure squamous cell carcinoma, an exceedingly rare subtype in itself.6 The underlying mechanism for the progression and development of ASC is unknown and debated. Although more than two thirds of the cases of ASC originate in patients with previously diagnosed adenocarcinoma of the prostate who have been treated with additional endocrine/radiation therapy, it is extremely rare to find a primary case of this particular subtype.7 Although some believe that hormone treatment/radiation therapy induce squamous metaplasia in the glandular cells of adenomatous prostate cancer, others contend that ASC develops de novo from divergent differentiation of epithelial stem cell lines within the prostatic cells.8 Figure 2 Contrast-Enhanced Computed Tomographic Scan Showing Grossly Enlarged Prostate With Heterogeneous Enhancement and Invading Rectum, Seminal Vesicles, and Urinary Bladder
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Clinical Genitourinary Cancer February 2014
Figure 3 Bone Scan Showing Multiple Osteolytic Bone Lesions With Increased Vascularity
ASC is defined by the presence of both glandular and squamous components on histologic examination. The squamous elements of ASC constitute an average of 40% of tumor volume but can range from 5% to 95%.9 Immunohistochemical staining is very helpful in demonstrating various types of cells in ASC. Stains such as PSA, prostate-specific acid phosphatase, and low-molecular-weight keratin (CAM5.3) are commonly found only in the glandular component of ASC, and therefore patients with a large squamous fraction can have normal levels of PSA, further delaying the diagnosis.5 Similarly, the squamous portion can stain positive for highmolecular-weight keratin (AE3).10 Additionally, glandular components have a tendency to be higher grade, with an average Gleason score of > 6; however, this is also a controversial point, because some have suggested that Gleason scoring should not be applied to this subtype.9 ASC tends to follow the traditional metastatic pathways similar to adenocarcinoma of the prostate, starting with local invasion and then spreading to bone and other distant soft tissue sites. However, a notable difference is that unlike standard prostatic adenocarcinoma, bone metastatic sites are characteristically osteolytic rather than osteoblastic in nature.5 ASC is an extremely aggressive subtype of prostate cancer, and in most cases there is metastasis at the time of diagnosis, as was the case in our patient. The disease is highly resistant to radiation
Shwetank Mishra et al and chemotherapy. In those individuals fortunate enough to be diagnosed early with localized/regional disease, prostatectomy shows some survival advantages.2 It is not clear whether hormone ablation is an effective treatment modality, because some authors suggest an early response, whereas others have noted that patients are refractory to hormone deprivation. Long-term survival is extremely poor. Wang et al found that the median cancer-specific survival was 16 months.2 For patients who presented with distant metastasis, the 6-month survival rate was only 20%, with all patients dying within 1 year of diagnosis. Although literature on the subject of ASC is limited, it appears that the best initial treatment for this particular type of cancer is aggressive surgical intervention in patients with regionally restricted disease. However, because of the highly aggressive nature of this disease in most cases, such as this one, patients present with widely disseminated disease and are advised to undergo hormone ablation therapy. Currently, there are no recommended chemotherapeutic regimens targeted at ASC.
Conclusion Primary ASC of the prostate is a very rare and aggressive form of prostate cancer, making up < 1% of all prostate malignancies. Since
PSA levels usually are not elevated, prompt suspicion is required to diagnose this condition.
Disclosure The authors have stated that they have no conflicts of interest.
References 1. Thompson GJ. Transurethral resection of malignant lesions of prostate gland. JAMA 1942; 120:1105-9. 2. Wang J, Wang FW, LaGrange CA, et al. Clinical features and outcomes of 25 patients with primary ASC of the prostate. Rare Tumors 2010; 2:e47. 3. Acetta PA, Gardner WA Jr. Adenosquamous carcinoma of the prostate. Urology 1983; 22:73-5. 4. Bassler TJ, Orozco R, Bassler IC, Boyle LM, Bormes T. Adenosquamous carcinoma of the prostate: case report with DNA analysis, immunochemistry, and literature review. Urology 1994; 53:832-4. 5. Humphrey PA. Histological variants of prostatic carcinoma and their significance. Histopathology 2012; 60:59-74. 6. Marcus DM, Goodman M, Jani AB, et al. A comprehensive review of incidence and survival in patients with rare histological variants of prostate cancer in the United States from 1973 to 2008. Prostate Cancer Prostatic Dis 2012; 15:283-8. 7. Mazzucchelli R, Lopez-Beltran A, Cheng L, et al. Rare and unusual histological variants of prostatic carcinoma: clinical significance. BJU Int 2008; 102:1369-74. 8. Egilmez T, Bal N, Guvel S, et al. Adenosquamous carcinoma of the prostate. Int J Urol 2005; 12:319-21. 9. Parwani AV, Kronz JD, Genega EM, et al. Prostate carcinoma with squamous differentiation: an analysis of 33 cases. Am J Surg Pathol 2004; 28:651-7. 10. Gattuso P, Carson HJ, Candel A, et al. Adenosquamous carcinoma of the prostate. Hum Pathol 1995; 26:123-6.
Clinical Genitourinary Cancer February 2014
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Primary Adenosquamous Carcinoma of the Prostate: A Rare Aggressive Tumor Shwetank Mishra, Hemant Goel, Nipun Awasthi, Anurag Puri, Rajkumar Mahapatra, D.K. PAL Clinical Practice Points Primary adenosquamous cell carcinoma (ASC) of the
prostate is a very rare and aggressive form of prostate cancer, making up < 1% of all diagnoses. Since its initial description by Thompson in 1942, there have been fewer than 30 cases reported in the literature. Recent reports of age-adjusted incidence rates of ASC have been shown to be about 0.03 cases per million per year making it less prevalent than pure squamous cell carcinoma, an exceedingly rare subtype in itself. The histogenesis of this tumor remains uncertain. The stimulus for the development of the squamous metaplastic cells had been thought to be related to hormone therapy or radiation therapy, or both.
However, we report a case of ASC arising spontaneously in a 60-year-old man with no previous history of risk of exposure. A close scrutiny shows that 4 of the 12 well-established cases lack a history of such therapy. In primary ASC of the prostate, the prostate-specific antigen PSA level is usually within normal range, so digital rectal examination and a high index of suspicion become part and parcel of diagnosing such rare carcinomas, as was found in this case. In addition to this diagnostic dilemma, urologists also find it difficult to manage such cases owing to lack of a definite treatment protocol resulting from the rarity of such tumors.
Clinical Genitourinary Cancer, Vol. 12, No. 1, e29-31 ª 2014 Elsevier Inc. All rights reserved. Keywords: Adenosquamous, Carcinoma, Prostate
Introduction Primary adenosquamous cell carcinoma (ASC) of the prostate is a very rare and aggressive form of prostate cancer. Since its initial description by Thompson in 1942, fewer than 30 cases had been reported in the literature.1 Although the majority of these cases arise subsequent to hormonal or radiation treatment with squamous differentiation, approximately one third of cases arise in a de novo setting.2-4 We report a case of ASC arising spontaneously in a 60year-old man with no previous risk factors.
Case Report A 60-year-old man presented with chief complaints of irritative/ storage lower urinary tract symptoms, low back pain, and 2 episodes of hematuria. He had no voiding lower urinary tract symptoms, Department of Urology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India Submitted: Mar 25, 2013; Revised: Aug 8, 2013; Accepted: Aug 27, 2013; Epub: Oct 19, 2013 Address for correspondence: Shwetank Mishra, MS, Department of Urology, Institute of Post Graduate Medical Education and Research, Kolkata-700020, West Bengal, India E-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2013.08.006
dysuria, graveluria, or history of urinary retention. There was no significant medical or family history. On digital rectal examination, the prostate was enlarged and nontender, with no discernible nodules but a hard consistency. The serum PSA level was 2.14 ng/ mL. On a transrectal ultrasonographically guided prostate biopsy sample, moderately differentiated ASC of the prostate with perineural invasion was revealed. About 65% of the prostatic tissue present in the biopsy sample was involved (Fig. 1). A contrastenhanced computed tomographic scan of the abdomen and pelvis showed a grossly enlarged prostate with heterogeneous enhancement and invading rectum, seminal vesicles, and urinary bladder (Fig. 2). A bone scan revealed multiple osteolytic bone lesions with increased vascularity favoring a neoplastic cause (Fig. 3). Liver function test results and chest radiography were normal. Because of the extensive metastatic nature of the disease along with bone pain, androgen deprivation therapy was started. We followed the patient with PSA values every 3 months, but they remained < 4 ng/mL. The patient died 9 months after confirmation of the diagnosis.
Discussion ASC of the prostate is 1 of the rarest and most aggressive subtypes of prostate cancer.5 Recent reports of age-adjusted incidence rates of
Clinical Genitourinary Cancer February 2014
- e29
Primary Adenosquamous Carcinoma of the Prostate Figure 1 Histopathologic Slide Showing Both Adenomatous and Squamous Elements
ASC have been shown to be about 0.03 cases per million individuals per year, making it less prevalent than pure squamous cell carcinoma, an exceedingly rare subtype in itself.6 The underlying mechanism for the progression and development of ASC is unknown and debated. Although more than two thirds of the cases of ASC originate in patients with previously diagnosed adenocarcinoma of the prostate who have been treated with additional endocrine/radiation therapy, it is extremely rare to find a primary case of this particular subtype.7 Although some believe that hormone treatment/radiation therapy induce squamous metaplasia in the glandular cells of adenomatous prostate cancer, others contend that ASC develops de novo from divergent differentiation of epithelial stem cell lines within the prostatic cells.8 Figure 2 Contrast-Enhanced Computed Tomographic Scan Showing Grossly Enlarged Prostate With Heterogeneous Enhancement and Invading Rectum, Seminal Vesicles, and Urinary Bladder
e30
-
Clinical Genitourinary Cancer February 2014
Figure 3 Bone Scan Showing Multiple Osteolytic Bone Lesions With Increased Vascularity
ASC is defined by the presence of both glandular and squamous components on histologic examination. The squamous elements of ASC constitute an average of 40% of tumor volume but can range from 5% to 95%.9 Immunohistochemical staining is very helpful in demonstrating various types of cells in ASC. Stains such as PSA, prostate-specific acid phosphatase, and low-molecular-weight keratin (CAM5.3) are commonly found only in the glandular component of ASC, and therefore patients with a large squamous fraction can have normal levels of PSA, further delaying the diagnosis.5 Similarly, the squamous portion can stain positive for highmolecular-weight keratin (AE3).10 Additionally, glandular components have a tendency to be higher grade, with an average Gleason score of > 6; however, this is also a controversial point, because some have suggested that Gleason scoring should not be applied to this subtype.9 ASC tends to follow the traditional metastatic pathways similar to adenocarcinoma of the prostate, starting with local invasion and then spreading to bone and other distant soft tissue sites. However, a notable difference is that unlike standard prostatic adenocarcinoma, bone metastatic sites are characteristically osteolytic rather than osteoblastic in nature.5 ASC is an extremely aggressive subtype of prostate cancer, and in most cases there is metastasis at the time of diagnosis, as was the case in our patient. The disease is highly resistant to radiation
Shwetank Mishra et al and chemotherapy. In those individuals fortunate enough to be diagnosed early with localized/regional disease, prostatectomy shows some survival advantages.2 It is not clear whether hormone ablation is an effective treatment modality, because some authors suggest an early response, whereas others have noted that patients are refractory to hormone deprivation. Long-term survival is extremely poor. Wang et al found that the median cancer-specific survival was 16 months.2 For patients who presented with distant metastasis, the 6-month survival rate was only 20%, with all patients dying within 1 year of diagnosis. Although literature on the subject of ASC is limited, it appears that the best initial treatment for this particular type of cancer is aggressive surgical intervention in patients with regionally restricted disease. However, because of the highly aggressive nature of this disease in most cases, such as this one, patients present with widely disseminated disease and are advised to undergo hormone ablation therapy. Currently, there are no recommended chemotherapeutic regimens targeted at ASC.
Conclusion Primary ASC of the prostate is a very rare and aggressive form of prostate cancer, making up < 1% of all prostate malignancies. Since
PSA levels usually are not elevated, prompt suspicion is required to diagnose this condition.
Disclosure The authors have stated that they have no conflicts of interest.
References 1. Thompson GJ. Transurethral resection of malignant lesions of prostate gland. JAMA 1942; 120:1105-9. 2. Wang J, Wang FW, LaGrange CA, et al. Clinical features and outcomes of 25 patients with primary ASC of the prostate. Rare Tumors 2010; 2:e47. 3. Acetta PA, Gardner WA Jr. Adenosquamous carcinoma of the prostate. Urology 1983; 22:73-5. 4. Bassler TJ, Orozco R, Bassler IC, Boyle LM, Bormes T. Adenosquamous carcinoma of the prostate: case report with DNA analysis, immunochemistry, and literature review. Urology 1994; 53:832-4. 5. Humphrey PA. Histological variants of prostatic carcinoma and their significance. Histopathology 2012; 60:59-74. 6. Marcus DM, Goodman M, Jani AB, et al. A comprehensive review of incidence and survival in patients with rare histological variants of prostate cancer in the United States from 1973 to 2008. Prostate Cancer Prostatic Dis 2012; 15:283-8. 7. Mazzucchelli R, Lopez-Beltran A, Cheng L, et al. Rare and unusual histological variants of prostatic carcinoma: clinical significance. BJU Int 2008; 102:1369-74. 8. Egilmez T, Bal N, Guvel S, et al. Adenosquamous carcinoma of the prostate. Int J Urol 2005; 12:319-21. 9. Parwani AV, Kronz JD, Genega EM, et al. Prostate carcinoma with squamous differentiation: an analysis of 33 cases. Am J Surg Pathol 2004; 28:651-7. 10. Gattuso P, Carson HJ, Candel A, et al. Adenosquamous carcinoma of the prostate. Hum Pathol 1995; 26:123-6.
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