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Cutaneous Metastasis of an Undiagnosed Prostatic Adenocarcinoma
Cutaneous Metastasis of an Undiagnosed Prostatic Adenocarcinoma
To the Editor:
Cutaneous metastasis of prostate cancer is rare and portends a bleak prognosis. Diagnosis of the primary cancer can be challenging, as skin metastasis can mimic a variety of conditions. We report a case of metastatic prostatic adenocarcinoma confirmed via biopsy of a new skin lesion.
A 97-year-old man presented to the dermatology clinic for routine follow-up of psoriasis. During the visit, a family member mentioned a new bleeding lesion on the left shoulder. It was not known how long the lesion had been present. Four months prior, the patient had a prostate-specific antigen (PSA) level of 582 ng/mL (reference range, 0-6.5 ng/mL), and computed tomography of the chest had shown innumerable pulmonary nodules in addition to lymphadenopathy of the left axilla, clavicle, and mediastinum. The imaging was ordered by the patient’s urologist as part of routine workup, as he had a history of obstructive renal failure and was being monitored for an indwelling catheter. Two months later, a bone scan ordered by the urologist due to high PSA levels showed extensive osteoblastic metastatic disease throughout the axial and proximal appendicular skeleton. The elevated PSA levels and findings of pulmonary and osteoblastic metastasis suggested a diagnosis of metastatic prostatic adenocarcinoma, but no confirmatory biopsy was performed following the imaging because the patient’s family declined additional workup or intervention.
Physical examination at the current presentation revealed an 8-mm brown papule with an overlying blue-white veil (Figure 1). There were no other skin findings. Primary differential diagnoses included metastatic prostate cancer, nodular melanoma, and traumatized seborrheic keratosis. A shave biopsy of the lesion showed multiple glandular structures infiltrating the dermis lined by monomorphic epithelial cells with prominent eosinophilic nucleoli (Figures 2 and 3). Focal cribriform architecture of the glands was present as well as dermal hemorrhage and a lymphohistiocytic infiltrate (Figure 2A). Interestingly, in-transit vascular metastases were confirmed with the support of ERG, CD34, and CD31 immunohistochemical staining of the vessels.



Immunohistochemical staining was positive for PSA (Figure 2B), NKX 3.1, and ERG in the invasive glandular structures, which also displayed patchy weak staining with AMACR. Staining was negative for prostein, cytokeratin (CK) 7, CK20, CK5/6, p63, p40, CDX2, and thyroid transcription factor 1. These findings were consistent with a diagnosis of cutaneous metastatic prostatic adenocarcinoma. Next-generation sequencing showed trans-membrane protease serine 2:v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) fusion compatible with the positive ERG immunohistochemical staining. The patient and family declined any treatment due to his age, comorbidities, and rapid decline. He died 2 months after diagnosis of the skin metastasis.
Aside from nonmelanoma skin cancer, prostate cancer is the most common cancer and the second leading cause of cancer-related deaths among men in the United States.1 It most commonly metastasizes to the bones, nonregional lymph nodes, liver, and thorax.2 Metastasis to the skin is very rare, with only a 0.36% incidence.3 When prostate cancer does metastasize to the skin, the prognosis is poor, with an estimated mean survival of 7 months after diagnosis of cutaneous metastasis.4 Our patient’s survival time was even shorter—only 2 months after diagnosis of cutaneous metastasis, likely the result of his late diagnosis.
Clinically, cutaneous metastasis of prostate cancer can manifest as a wide variety of lesions; in one report of 78 cases, 56 (72%) were hard nodules, 11 (14%) were single nodules, 5 (7%) were edema or lymphedema, and 5 (7%) were an unspecific rash.4 Diagnosis of cutaneous metastasis of prostate cancer can be challenging, as it often is mistaken for other skin conditions including herpes zoster, basal cell carcinoma, angiosarcoma, cellulitis, mammary Paget disease, telangiectasia, pyoderma, morphea, and trichoepithelioma.5 In our patient, the clinical appearance of the lesion resembled a nodular melanoma. Thus, in patients with a history of prostate cancer, it is important to keep cutaneous metastasis in the differential when examining the skin because of the prognostic implications. Cutaneous metastasis of prostate cancer often indicates a poor prognosis.
In a report of 78 patients, the most common sites of skin metastasis for prostate cancer were the inguinal area and penis (28% [22/78]), abdomen (23% [18/78]), head and neck (16% [12/78]), and chest (14% [11/78]); the extremities and back were less frequently involved (10% [8/78] and 9% [7/78], respectively).4 Generally, cutaneous metastasis of internal malignancies involves the deep dermis and the subcutaneous tissue. It is common for cutaneous metastases to show histologic features of the primary tumor, as we saw in our patient. In a case series with 45 histologic diagnoses of cutaneous metastases from internal malignancies, 75.5% (34/45) of cases showed morphologic features of the primary tumor.6 However, this is not always the case, and the histologic appearance may vary. Metastatic prostate cancer may manifest as sheets, nests, or cords and often may have nuclear pleomorphism with prominent nucleoli.7
Immunohistochemical staining can help make a definitive diagnosis and differentiate the source of the tumor. Prostate cancer metastases often will stain positive for NKX3.1, PSA, AMACR, ERG, PSMA, and prosaposin, with PSA being the most specific marker.7,8 In our patient, no prostate biopsy had been performed, thus the skin biopsy was the diagnostic tissue for the prostatic adenocarcinoma.
Next-generation sequencing showed a TMPRSS2- ERG fusion, which commonly is seen in prostate cancer.9 A search of Google Scholar using the terms next-generation sequencing, cutaneous metastasis, and prostate adenocarcinoma yielded 3 additional cases of cutaneous metastasis of prostate cancer in which next-generation sequencing was performed.10-12 One case showed mutations of the tumor protein 53 (TP53) and phosphatase and tensin homolog (PTEN) genes; one showed just a TP53 mutation; and one showed inactivation of the breast cancer predisposition gene 2 (BRCA2) and amplification of MYC proto-oncogene, BHLH transcription factor (MYC) and fibroblast growth factor receptor 1 (FGFR1).10,11,12 While limited by a small number of reported cases, there does not appear to be a repeating mutation to suggest a genetic mechanism of skin metastasis.
The route of cutaneous metastasis of prostate cancer still is unclear, but hypothesized mechanisms include hematogenous or lymphatic spread, direct infiltration, or implantation from a surgical scar.11 When cutaneous involvement occurs in an area far from the primary tumor, it is thought to be the result of hematogenous spread, which would be consistent with our patient’s findings.13 Given the role of Batson venous plexus as a conduit from the prostate to the vertebral column for metastatic spread and considering the location of the lesion on our patient’s back, we hypothesized that the mechanism of metastasis to the skin was from vascular extension of the metastatic foci involving the vertebrae.
Our case highlights the importance of considering cutaneous involvement of prostatic adenocarcinoma in patients with new skin lesions, particularly in the setting of a known or suspected prostate malignancy. Skin metastasis can have a range of manifestations and provides prognostic information that can help determine the course of treatment.
- US Cancer Statistics Working Group. US cancer statistics data visualizations tool, based on 2022 submission data (1999-2020). US Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. November 2023. Accessed November 11, 2024. https://www.cdc.gov/cancer/dataviz
- Gandaglia G, Abdollah F, Schiffmann J, et al. Distribution of metastatic sites in patients with prostate cancer: a population-based analysis. Prostate. 2014;74:210-216. doi:10.1002/pros.22742
- Mueller TJ, Wu H, Greenberg RE, et al. Cutaneous metastases from genitourinary malignancies. Urology. 2004;63:1021-1026. doi:10.1016/j.urology.2004.01.014
- Wang SQ, Mecca PS, Myskowski PL, et al. Scrotal and penile papules and plaques as the initial manifestation of a cutaneous metastasis of adenocarcinoma of the prostate: case report and review of the literature. J Cutan Pathol. 2008;35:681-684. doi:10.1111/j.1600-0560.2007.00873.x
- Reddy S, Bang RH, Contreras ME. Telangiectatic cutaneous metastasis from carcinoma of the prostate. Br J Dermatol. 2007;156:598-600. doi:10.1111/j.1365-2133.2006.07696.x
- Guanziroli E, Coggi A, Venegoni L, et al. Cutaneous metastases of internal malignancies: an experience from a single institution. Eur J Dermatol. 2017;27:609-614. doi:10.1684/ejd.2017.3142
- Onalaja-Underwood AA, Sokumbi O. Eruptive papules as a cutaneous manifestation of metastatic prostate adenocarcinoma. Am J Dermatopathol. 2023;45:828-830. doi:10.1097/DAD.0000000000002559
- Oesterling JE. Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol. 1991;145:907-923. doi:10.1016/s0022-5347(17)38491-4
- Wang Z, Wang Y, Zhang J, et al. Significance of the TMPRSS2:ERG gene fusion in prostate cancer. Mol Med Rep. 2017;16:5450-5458. doi:10.3892/mmr.2017.7281
- Sharma H, Franklin M, Braunberger R, et al. Cutaneous metastasis from prostate cancer: a case report with literature review. Curr Probl Cancer Case Rep. 2022;7:100175. doi:10.1016/j.cpccr.2022.100175
- Dills A, Obi O, Bustos K, et al. Cutaneous manifestation of prostate adenocarcinoma: a rare presentation of a common disease. J Investig Med High Impact Case Rep. 2021;9:2324709621990769. doi:10.1177/2324709621990769
- Fadel CA, Kallab AM. Cutaneous scrotal metastasis secondary to primary prostate adenocarcinoma responding to immunotherapy. Ann Intern Med: Clinical Cases. 2022;1. doi:10.7326/aimcc.2022.0682
- Powell FC, Venencie PY, Winkelmann RK. Metastatic prostate carcinoma manifesting as penile nodules. Arch Dermatol. 1984;120:1604- 1606. doi:10.1001/archderm.1984.01650480066022
To the Editor:
Cutaneous metastasis of prostate cancer is rare and portends a bleak prognosis. Diagnosis of the primary cancer can be challenging, as skin metastasis can mimic a variety of conditions. We report a case of metastatic prostatic adenocarcinoma confirmed via biopsy of a new skin lesion.
A 97-year-old man presented to the dermatology clinic for routine follow-up of psoriasis. During the visit, a family member mentioned a new bleeding lesion on the left shoulder. It was not known how long the lesion had been present. Four months prior, the patient had a prostate-specific antigen (PSA) level of 582 ng/mL (reference range, 0-6.5 ng/mL), and computed tomography of the chest had shown innumerable pulmonary nodules in addition to lymphadenopathy of the left axilla, clavicle, and mediastinum. The imaging was ordered by the patient’s urologist as part of routine workup, as he had a history of obstructive renal failure and was being monitored for an indwelling catheter. Two months later, a bone scan ordered by the urologist due to high PSA levels showed extensive osteoblastic metastatic disease throughout the axial and proximal appendicular skeleton. The elevated PSA levels and findings of pulmonary and osteoblastic metastasis suggested a diagnosis of metastatic prostatic adenocarcinoma, but no confirmatory biopsy was performed following the imaging because the patient’s family declined additional workup or intervention.
Physical examination at the current presentation revealed an 8-mm brown papule with an overlying blue-white veil (Figure 1). There were no other skin findings. Primary differential diagnoses included metastatic prostate cancer, nodular melanoma, and traumatized seborrheic keratosis. A shave biopsy of the lesion showed multiple glandular structures infiltrating the dermis lined by monomorphic epithelial cells with prominent eosinophilic nucleoli (Figures 2 and 3). Focal cribriform architecture of the glands was present as well as dermal hemorrhage and a lymphohistiocytic infiltrate (Figure 2A). Interestingly, in-transit vascular metastases were confirmed with the support of ERG, CD34, and CD31 immunohistochemical staining of the vessels.



Immunohistochemical staining was positive for PSA (Figure 2B), NKX 3.1, and ERG in the invasive glandular structures, which also displayed patchy weak staining with AMACR. Staining was negative for prostein, cytokeratin (CK) 7, CK20, CK5/6, p63, p40, CDX2, and thyroid transcription factor 1. These findings were consistent with a diagnosis of cutaneous metastatic prostatic adenocarcinoma. Next-generation sequencing showed trans-membrane protease serine 2:v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) fusion compatible with the positive ERG immunohistochemical staining. The patient and family declined any treatment due to his age, comorbidities, and rapid decline. He died 2 months after diagnosis of the skin metastasis.
Aside from nonmelanoma skin cancer, prostate cancer is the most common cancer and the second leading cause of cancer-related deaths among men in the United States.1 It most commonly metastasizes to the bones, nonregional lymph nodes, liver, and thorax.2 Metastasis to the skin is very rare, with only a 0.36% incidence.3 When prostate cancer does metastasize to the skin, the prognosis is poor, with an estimated mean survival of 7 months after diagnosis of cutaneous metastasis.4 Our patient’s survival time was even shorter—only 2 months after diagnosis of cutaneous metastasis, likely the result of his late diagnosis.
Clinically, cutaneous metastasis of prostate cancer can manifest as a wide variety of lesions; in one report of 78 cases, 56 (72%) were hard nodules, 11 (14%) were single nodules, 5 (7%) were edema or lymphedema, and 5 (7%) were an unspecific rash.4 Diagnosis of cutaneous metastasis of prostate cancer can be challenging, as it often is mistaken for other skin conditions including herpes zoster, basal cell carcinoma, angiosarcoma, cellulitis, mammary Paget disease, telangiectasia, pyoderma, morphea, and trichoepithelioma.5 In our patient, the clinical appearance of the lesion resembled a nodular melanoma. Thus, in patients with a history of prostate cancer, it is important to keep cutaneous metastasis in the differential when examining the skin because of the prognostic implications. Cutaneous metastasis of prostate cancer often indicates a poor prognosis.
In a report of 78 patients, the most common sites of skin metastasis for prostate cancer were the inguinal area and penis (28% [22/78]), abdomen (23% [18/78]), head and neck (16% [12/78]), and chest (14% [11/78]); the extremities and back were less frequently involved (10% [8/78] and 9% [7/78], respectively).4 Generally, cutaneous metastasis of internal malignancies involves the deep dermis and the subcutaneous tissue. It is common for cutaneous metastases to show histologic features of the primary tumor, as we saw in our patient. In a case series with 45 histologic diagnoses of cutaneous metastases from internal malignancies, 75.5% (34/45) of cases showed morphologic features of the primary tumor.6 However, this is not always the case, and the histologic appearance may vary. Metastatic prostate cancer may manifest as sheets, nests, or cords and often may have nuclear pleomorphism with prominent nucleoli.7
Immunohistochemical staining can help make a definitive diagnosis and differentiate the source of the tumor. Prostate cancer metastases often will stain positive for NKX3.1, PSA, AMACR, ERG, PSMA, and prosaposin, with PSA being the most specific marker.7,8 In our patient, no prostate biopsy had been performed, thus the skin biopsy was the diagnostic tissue for the prostatic adenocarcinoma.
Next-generation sequencing showed a TMPRSS2- ERG fusion, which commonly is seen in prostate cancer.9 A search of Google Scholar using the terms next-generation sequencing, cutaneous metastasis, and prostate adenocarcinoma yielded 3 additional cases of cutaneous metastasis of prostate cancer in which next-generation sequencing was performed.10-12 One case showed mutations of the tumor protein 53 (TP53) and phosphatase and tensin homolog (PTEN) genes; one showed just a TP53 mutation; and one showed inactivation of the breast cancer predisposition gene 2 (BRCA2) and amplification of MYC proto-oncogene, BHLH transcription factor (MYC) and fibroblast growth factor receptor 1 (FGFR1).10,11,12 While limited by a small number of reported cases, there does not appear to be a repeating mutation to suggest a genetic mechanism of skin metastasis.
The route of cutaneous metastasis of prostate cancer still is unclear, but hypothesized mechanisms include hematogenous or lymphatic spread, direct infiltration, or implantation from a surgical scar.11 When cutaneous involvement occurs in an area far from the primary tumor, it is thought to be the result of hematogenous spread, which would be consistent with our patient’s findings.13 Given the role of Batson venous plexus as a conduit from the prostate to the vertebral column for metastatic spread and considering the location of the lesion on our patient’s back, we hypothesized that the mechanism of metastasis to the skin was from vascular extension of the metastatic foci involving the vertebrae.
Our case highlights the importance of considering cutaneous involvement of prostatic adenocarcinoma in patients with new skin lesions, particularly in the setting of a known or suspected prostate malignancy. Skin metastasis can have a range of manifestations and provides prognostic information that can help determine the course of treatment.
To the Editor:
Cutaneous metastasis of prostate cancer is rare and portends a bleak prognosis. Diagnosis of the primary cancer can be challenging, as skin metastasis can mimic a variety of conditions. We report a case of metastatic prostatic adenocarcinoma confirmed via biopsy of a new skin lesion.
A 97-year-old man presented to the dermatology clinic for routine follow-up of psoriasis. During the visit, a family member mentioned a new bleeding lesion on the left shoulder. It was not known how long the lesion had been present. Four months prior, the patient had a prostate-specific antigen (PSA) level of 582 ng/mL (reference range, 0-6.5 ng/mL), and computed tomography of the chest had shown innumerable pulmonary nodules in addition to lymphadenopathy of the left axilla, clavicle, and mediastinum. The imaging was ordered by the patient’s urologist as part of routine workup, as he had a history of obstructive renal failure and was being monitored for an indwelling catheter. Two months later, a bone scan ordered by the urologist due to high PSA levels showed extensive osteoblastic metastatic disease throughout the axial and proximal appendicular skeleton. The elevated PSA levels and findings of pulmonary and osteoblastic metastasis suggested a diagnosis of metastatic prostatic adenocarcinoma, but no confirmatory biopsy was performed following the imaging because the patient’s family declined additional workup or intervention.
Physical examination at the current presentation revealed an 8-mm brown papule with an overlying blue-white veil (Figure 1). There were no other skin findings. Primary differential diagnoses included metastatic prostate cancer, nodular melanoma, and traumatized seborrheic keratosis. A shave biopsy of the lesion showed multiple glandular structures infiltrating the dermis lined by monomorphic epithelial cells with prominent eosinophilic nucleoli (Figures 2 and 3). Focal cribriform architecture of the glands was present as well as dermal hemorrhage and a lymphohistiocytic infiltrate (Figure 2A). Interestingly, in-transit vascular metastases were confirmed with the support of ERG, CD34, and CD31 immunohistochemical staining of the vessels.



Immunohistochemical staining was positive for PSA (Figure 2B), NKX 3.1, and ERG in the invasive glandular structures, which also displayed patchy weak staining with AMACR. Staining was negative for prostein, cytokeratin (CK) 7, CK20, CK5/6, p63, p40, CDX2, and thyroid transcription factor 1. These findings were consistent with a diagnosis of cutaneous metastatic prostatic adenocarcinoma. Next-generation sequencing showed trans-membrane protease serine 2:v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) fusion compatible with the positive ERG immunohistochemical staining. The patient and family declined any treatment due to his age, comorbidities, and rapid decline. He died 2 months after diagnosis of the skin metastasis.
Aside from nonmelanoma skin cancer, prostate cancer is the most common cancer and the second leading cause of cancer-related deaths among men in the United States.1 It most commonly metastasizes to the bones, nonregional lymph nodes, liver, and thorax.2 Metastasis to the skin is very rare, with only a 0.36% incidence.3 When prostate cancer does metastasize to the skin, the prognosis is poor, with an estimated mean survival of 7 months after diagnosis of cutaneous metastasis.4 Our patient’s survival time was even shorter—only 2 months after diagnosis of cutaneous metastasis, likely the result of his late diagnosis.
Clinically, cutaneous metastasis of prostate cancer can manifest as a wide variety of lesions; in one report of 78 cases, 56 (72%) were hard nodules, 11 (14%) were single nodules, 5 (7%) were edema or lymphedema, and 5 (7%) were an unspecific rash.4 Diagnosis of cutaneous metastasis of prostate cancer can be challenging, as it often is mistaken for other skin conditions including herpes zoster, basal cell carcinoma, angiosarcoma, cellulitis, mammary Paget disease, telangiectasia, pyoderma, morphea, and trichoepithelioma.5 In our patient, the clinical appearance of the lesion resembled a nodular melanoma. Thus, in patients with a history of prostate cancer, it is important to keep cutaneous metastasis in the differential when examining the skin because of the prognostic implications. Cutaneous metastasis of prostate cancer often indicates a poor prognosis.
In a report of 78 patients, the most common sites of skin metastasis for prostate cancer were the inguinal area and penis (28% [22/78]), abdomen (23% [18/78]), head and neck (16% [12/78]), and chest (14% [11/78]); the extremities and back were less frequently involved (10% [8/78] and 9% [7/78], respectively).4 Generally, cutaneous metastasis of internal malignancies involves the deep dermis and the subcutaneous tissue. It is common for cutaneous metastases to show histologic features of the primary tumor, as we saw in our patient. In a case series with 45 histologic diagnoses of cutaneous metastases from internal malignancies, 75.5% (34/45) of cases showed morphologic features of the primary tumor.6 However, this is not always the case, and the histologic appearance may vary. Metastatic prostate cancer may manifest as sheets, nests, or cords and often may have nuclear pleomorphism with prominent nucleoli.7
Immunohistochemical staining can help make a definitive diagnosis and differentiate the source of the tumor. Prostate cancer metastases often will stain positive for NKX3.1, PSA, AMACR, ERG, PSMA, and prosaposin, with PSA being the most specific marker.7,8 In our patient, no prostate biopsy had been performed, thus the skin biopsy was the diagnostic tissue for the prostatic adenocarcinoma.
Next-generation sequencing showed a TMPRSS2- ERG fusion, which commonly is seen in prostate cancer.9 A search of Google Scholar using the terms next-generation sequencing, cutaneous metastasis, and prostate adenocarcinoma yielded 3 additional cases of cutaneous metastasis of prostate cancer in which next-generation sequencing was performed.10-12 One case showed mutations of the tumor protein 53 (TP53) and phosphatase and tensin homolog (PTEN) genes; one showed just a TP53 mutation; and one showed inactivation of the breast cancer predisposition gene 2 (BRCA2) and amplification of MYC proto-oncogene, BHLH transcription factor (MYC) and fibroblast growth factor receptor 1 (FGFR1).10,11,12 While limited by a small number of reported cases, there does not appear to be a repeating mutation to suggest a genetic mechanism of skin metastasis.
The route of cutaneous metastasis of prostate cancer still is unclear, but hypothesized mechanisms include hematogenous or lymphatic spread, direct infiltration, or implantation from a surgical scar.11 When cutaneous involvement occurs in an area far from the primary tumor, it is thought to be the result of hematogenous spread, which would be consistent with our patient’s findings.13 Given the role of Batson venous plexus as a conduit from the prostate to the vertebral column for metastatic spread and considering the location of the lesion on our patient’s back, we hypothesized that the mechanism of metastasis to the skin was from vascular extension of the metastatic foci involving the vertebrae.
Our case highlights the importance of considering cutaneous involvement of prostatic adenocarcinoma in patients with new skin lesions, particularly in the setting of a known or suspected prostate malignancy. Skin metastasis can have a range of manifestations and provides prognostic information that can help determine the course of treatment.
- US Cancer Statistics Working Group. US cancer statistics data visualizations tool, based on 2022 submission data (1999-2020). US Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. November 2023. Accessed November 11, 2024. https://www.cdc.gov/cancer/dataviz
- Gandaglia G, Abdollah F, Schiffmann J, et al. Distribution of metastatic sites in patients with prostate cancer: a population-based analysis. Prostate. 2014;74:210-216. doi:10.1002/pros.22742
- Mueller TJ, Wu H, Greenberg RE, et al. Cutaneous metastases from genitourinary malignancies. Urology. 2004;63:1021-1026. doi:10.1016/j.urology.2004.01.014
- Wang SQ, Mecca PS, Myskowski PL, et al. Scrotal and penile papules and plaques as the initial manifestation of a cutaneous metastasis of adenocarcinoma of the prostate: case report and review of the literature. J Cutan Pathol. 2008;35:681-684. doi:10.1111/j.1600-0560.2007.00873.x
- Reddy S, Bang RH, Contreras ME. Telangiectatic cutaneous metastasis from carcinoma of the prostate. Br J Dermatol. 2007;156:598-600. doi:10.1111/j.1365-2133.2006.07696.x
- Guanziroli E, Coggi A, Venegoni L, et al. Cutaneous metastases of internal malignancies: an experience from a single institution. Eur J Dermatol. 2017;27:609-614. doi:10.1684/ejd.2017.3142
- Onalaja-Underwood AA, Sokumbi O. Eruptive papules as a cutaneous manifestation of metastatic prostate adenocarcinoma. Am J Dermatopathol. 2023;45:828-830. doi:10.1097/DAD.0000000000002559
- Oesterling JE. Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol. 1991;145:907-923. doi:10.1016/s0022-5347(17)38491-4
- Wang Z, Wang Y, Zhang J, et al. Significance of the TMPRSS2:ERG gene fusion in prostate cancer. Mol Med Rep. 2017;16:5450-5458. doi:10.3892/mmr.2017.7281
- Sharma H, Franklin M, Braunberger R, et al. Cutaneous metastasis from prostate cancer: a case report with literature review. Curr Probl Cancer Case Rep. 2022;7:100175. doi:10.1016/j.cpccr.2022.100175
- Dills A, Obi O, Bustos K, et al. Cutaneous manifestation of prostate adenocarcinoma: a rare presentation of a common disease. J Investig Med High Impact Case Rep. 2021;9:2324709621990769. doi:10.1177/2324709621990769
- Fadel CA, Kallab AM. Cutaneous scrotal metastasis secondary to primary prostate adenocarcinoma responding to immunotherapy. Ann Intern Med: Clinical Cases. 2022;1. doi:10.7326/aimcc.2022.0682
- Powell FC, Venencie PY, Winkelmann RK. Metastatic prostate carcinoma manifesting as penile nodules. Arch Dermatol. 1984;120:1604- 1606. doi:10.1001/archderm.1984.01650480066022
- US Cancer Statistics Working Group. US cancer statistics data visualizations tool, based on 2022 submission data (1999-2020). US Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. November 2023. Accessed November 11, 2024. https://www.cdc.gov/cancer/dataviz
- Gandaglia G, Abdollah F, Schiffmann J, et al. Distribution of metastatic sites in patients with prostate cancer: a population-based analysis. Prostate. 2014;74:210-216. doi:10.1002/pros.22742
- Mueller TJ, Wu H, Greenberg RE, et al. Cutaneous metastases from genitourinary malignancies. Urology. 2004;63:1021-1026. doi:10.1016/j.urology.2004.01.014
- Wang SQ, Mecca PS, Myskowski PL, et al. Scrotal and penile papules and plaques as the initial manifestation of a cutaneous metastasis of adenocarcinoma of the prostate: case report and review of the literature. J Cutan Pathol. 2008;35:681-684. doi:10.1111/j.1600-0560.2007.00873.x
- Reddy S, Bang RH, Contreras ME. Telangiectatic cutaneous metastasis from carcinoma of the prostate. Br J Dermatol. 2007;156:598-600. doi:10.1111/j.1365-2133.2006.07696.x
- Guanziroli E, Coggi A, Venegoni L, et al. Cutaneous metastases of internal malignancies: an experience from a single institution. Eur J Dermatol. 2017;27:609-614. doi:10.1684/ejd.2017.3142
- Onalaja-Underwood AA, Sokumbi O. Eruptive papules as a cutaneous manifestation of metastatic prostate adenocarcinoma. Am J Dermatopathol. 2023;45:828-830. doi:10.1097/DAD.0000000000002559
- Oesterling JE. Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol. 1991;145:907-923. doi:10.1016/s0022-5347(17)38491-4
- Wang Z, Wang Y, Zhang J, et al. Significance of the TMPRSS2:ERG gene fusion in prostate cancer. Mol Med Rep. 2017;16:5450-5458. doi:10.3892/mmr.2017.7281
- Sharma H, Franklin M, Braunberger R, et al. Cutaneous metastasis from prostate cancer: a case report with literature review. Curr Probl Cancer Case Rep. 2022;7:100175. doi:10.1016/j.cpccr.2022.100175
- Dills A, Obi O, Bustos K, et al. Cutaneous manifestation of prostate adenocarcinoma: a rare presentation of a common disease. J Investig Med High Impact Case Rep. 2021;9:2324709621990769. doi:10.1177/2324709621990769
- Fadel CA, Kallab AM. Cutaneous scrotal metastasis secondary to primary prostate adenocarcinoma responding to immunotherapy. Ann Intern Med: Clinical Cases. 2022;1. doi:10.7326/aimcc.2022.0682
- Powell FC, Venencie PY, Winkelmann RK. Metastatic prostate carcinoma manifesting as penile nodules. Arch Dermatol. 1984;120:1604- 1606. doi:10.1001/archderm.1984.01650480066022
Cutaneous Metastasis of an Undiagnosed Prostatic Adenocarcinoma
Cutaneous Metastasis of an Undiagnosed Prostatic Adenocarcinoma
PRACTICE POINTS
- Cutaneous metastasis of prostate cancer can have various manifestations and portends a poor prognosis.
- New skin lesions that develop in patients with a high clinical suspicion for prostate cancer warrant consideration of cutaneous metastasis.
Enoxaparin-Induced Hemorrhagic Bullae at Sites of Trauma and Endothelial Pathology
To the Editor:
A 67-year-old man with diabetes mellitus was admitted to the hospital for exacerbation of congestive heart failure and atrial flutter with rapid ventricular response. He subsequently developed a non-ST segment elevation myocardial infarction and was started on subcutaneous enoxaparin 110 mg twice daily. On day 9 of hospitalization, small “blood blisters” on the legs were noted by the nurse, and dermatology was consulted.
Physical examination revealed tense hemorrhagic bullae with erythematous haloes scattered over the arms and legs and to a lesser extent on the trunk. The bullae were most concentrated at the surrounding subcutaneous injection sites of insulin and enoxaparin with secondary bruising (Figure 1). The lesions also were present on the legs, where pitting edema and capillaritis also were appreciated (Figure 2).
Laboratory workup for heparin-induced thrombocytopenia was negative. A diagnosis of enoxaparin-associated hemorrhagic bullae was made. Biopsy was recommended, but the patient declined based on anecdotal reports that the bullae typically self-resolve.
The enoxaparin was discontinued 7 days after the dermatology consultation, and the patient was transitioned to apixaban. A review of the medical record during the dermatology consultation revealed he had been on aspirin (81–385 mg/d) for 13 years prior to admission and had received prophylactic enoxaparin (40 mg/d) while hospitalized 2 and 7 years prior to the current episode of hemorrhagic bullae.
The patient declined outpatient dermatology follow-up; however, his cardiologist noted that the skin lesions had resolved at a 3-week postdischarge appointment. Approximately 5 months after discharge, the patient was re-treated by the cardiologist with enoxaparin 110 mg twice daily for 3 days to bridge to warfarin after he developed a deep vein thrombosis while taking apixaban. He did not develop hemorrhagic bullae upon retreatment with enoxaparin.
Heparin-induced hemorrhagic bullous dermatosis (HBD) has been associated with administration of both unfractionated and low-molecular-weight heparin.1 The condition typically develops 5 to 21 days after initiation of heparin as asymptomatic, purple-to-black bullae, sometimes with an erythematous halo.2,3 The arms and legs are the most common location, but the exact pathogenesis of the lesions remains unknown.3,4 Most cases resolve within weeks of discontinuing heparin, although some reports have suggested that discontinuation is unnecessary.3,4
Histopathologic analysis shows intraepidermal or subepidermal bullae with red blood cells and fibrin in the absence of vasculitis and intravascular thrombi.1,4 Immunofluorescence studies are negative.3 In a comprehensive review of HBD, the investigators hypothesized that the pathogenesis may be related to noninflammatory to pauci-inflammatory activation of basement membrane zone proteases or possibly epithelial or endothelial fragility in conjunction with trauma that causes disruption of the vascular endothelium (eg, subcutaneous injections, vasculitis).4
Our case is of particular interest because the bullae were strikingly limited to sites of subcutaneous injection and surrounding areas along with coexistent endothelial pathology on the lower legs (capillaritis and pitting edema). These clinical observations support trauma from the injections and altered endothelia as pathogenetic factors in HBD.
Of interest, our patient had 2 prior hospitalizations during which he received prophylactic enoxaparin and did not develop hemorrhagic bullae. Furthermore, repeat exposure to therapeutic dosing of enoxaparin with a shorter duration did not result in recurrence of HBD. This suggests that heparin dosing and duration of therapy also might be involved in the development of HBD.
Our hope is that future reports of HBD will address the presence or absence of coexistent cutaneous pathology, such as edema, stasis dermatitis, bruising, and capillaritis, along with heparin dosing, duration, and prior exposure to heparin treatment so that risk factors and pathogenesis can be further investigated. We also agree with Snow et al4 that HBD should be included as an outcome in future trials of heparin therapy.
- Komforti MK, Bressler ES, Selim MA, et al. A rare cutaneous manifestation of hemorrhagic bullae to low-molecular-weight heparin and fondaparinux: report of two cases: letter to the editor. J Cutan Pathol. 2017;44:104-106. doi:10.1111/cup.12821
- Peña ZG, Suszko JW, Morrison LH. Hemorrhagic bullae in a 73-year-old man. JAMA Dermatol. 2013;149:871-872. doi:10.1001/jamadermatol.2013.3364a
- Gouveia AI, Lopes L, Soares-Almeida L, et al. Bullous hemorrhagic dermatosis induced by enoxaparin. Cutan Ocul Toxicol. 2016;35:160-162. doi:10.3109/15569527.2015.1041033
- Snow SC, Pearson DR, Fathi R, et al. Heparin‐induced haemorrhagic bullous dermatosis. Clin Exp Dermatol. 2018;43:393-398. doi:10.1111/ced.13327
To the Editor:
A 67-year-old man with diabetes mellitus was admitted to the hospital for exacerbation of congestive heart failure and atrial flutter with rapid ventricular response. He subsequently developed a non-ST segment elevation myocardial infarction and was started on subcutaneous enoxaparin 110 mg twice daily. On day 9 of hospitalization, small “blood blisters” on the legs were noted by the nurse, and dermatology was consulted.
Physical examination revealed tense hemorrhagic bullae with erythematous haloes scattered over the arms and legs and to a lesser extent on the trunk. The bullae were most concentrated at the surrounding subcutaneous injection sites of insulin and enoxaparin with secondary bruising (Figure 1). The lesions also were present on the legs, where pitting edema and capillaritis also were appreciated (Figure 2).
Laboratory workup for heparin-induced thrombocytopenia was negative. A diagnosis of enoxaparin-associated hemorrhagic bullae was made. Biopsy was recommended, but the patient declined based on anecdotal reports that the bullae typically self-resolve.
The enoxaparin was discontinued 7 days after the dermatology consultation, and the patient was transitioned to apixaban. A review of the medical record during the dermatology consultation revealed he had been on aspirin (81–385 mg/d) for 13 years prior to admission and had received prophylactic enoxaparin (40 mg/d) while hospitalized 2 and 7 years prior to the current episode of hemorrhagic bullae.
The patient declined outpatient dermatology follow-up; however, his cardiologist noted that the skin lesions had resolved at a 3-week postdischarge appointment. Approximately 5 months after discharge, the patient was re-treated by the cardiologist with enoxaparin 110 mg twice daily for 3 days to bridge to warfarin after he developed a deep vein thrombosis while taking apixaban. He did not develop hemorrhagic bullae upon retreatment with enoxaparin.
Heparin-induced hemorrhagic bullous dermatosis (HBD) has been associated with administration of both unfractionated and low-molecular-weight heparin.1 The condition typically develops 5 to 21 days after initiation of heparin as asymptomatic, purple-to-black bullae, sometimes with an erythematous halo.2,3 The arms and legs are the most common location, but the exact pathogenesis of the lesions remains unknown.3,4 Most cases resolve within weeks of discontinuing heparin, although some reports have suggested that discontinuation is unnecessary.3,4
Histopathologic analysis shows intraepidermal or subepidermal bullae with red blood cells and fibrin in the absence of vasculitis and intravascular thrombi.1,4 Immunofluorescence studies are negative.3 In a comprehensive review of HBD, the investigators hypothesized that the pathogenesis may be related to noninflammatory to pauci-inflammatory activation of basement membrane zone proteases or possibly epithelial or endothelial fragility in conjunction with trauma that causes disruption of the vascular endothelium (eg, subcutaneous injections, vasculitis).4
Our case is of particular interest because the bullae were strikingly limited to sites of subcutaneous injection and surrounding areas along with coexistent endothelial pathology on the lower legs (capillaritis and pitting edema). These clinical observations support trauma from the injections and altered endothelia as pathogenetic factors in HBD.
Of interest, our patient had 2 prior hospitalizations during which he received prophylactic enoxaparin and did not develop hemorrhagic bullae. Furthermore, repeat exposure to therapeutic dosing of enoxaparin with a shorter duration did not result in recurrence of HBD. This suggests that heparin dosing and duration of therapy also might be involved in the development of HBD.
Our hope is that future reports of HBD will address the presence or absence of coexistent cutaneous pathology, such as edema, stasis dermatitis, bruising, and capillaritis, along with heparin dosing, duration, and prior exposure to heparin treatment so that risk factors and pathogenesis can be further investigated. We also agree with Snow et al4 that HBD should be included as an outcome in future trials of heparin therapy.
To the Editor:
A 67-year-old man with diabetes mellitus was admitted to the hospital for exacerbation of congestive heart failure and atrial flutter with rapid ventricular response. He subsequently developed a non-ST segment elevation myocardial infarction and was started on subcutaneous enoxaparin 110 mg twice daily. On day 9 of hospitalization, small “blood blisters” on the legs were noted by the nurse, and dermatology was consulted.
Physical examination revealed tense hemorrhagic bullae with erythematous haloes scattered over the arms and legs and to a lesser extent on the trunk. The bullae were most concentrated at the surrounding subcutaneous injection sites of insulin and enoxaparin with secondary bruising (Figure 1). The lesions also were present on the legs, where pitting edema and capillaritis also were appreciated (Figure 2).
Laboratory workup for heparin-induced thrombocytopenia was negative. A diagnosis of enoxaparin-associated hemorrhagic bullae was made. Biopsy was recommended, but the patient declined based on anecdotal reports that the bullae typically self-resolve.
The enoxaparin was discontinued 7 days after the dermatology consultation, and the patient was transitioned to apixaban. A review of the medical record during the dermatology consultation revealed he had been on aspirin (81–385 mg/d) for 13 years prior to admission and had received prophylactic enoxaparin (40 mg/d) while hospitalized 2 and 7 years prior to the current episode of hemorrhagic bullae.
The patient declined outpatient dermatology follow-up; however, his cardiologist noted that the skin lesions had resolved at a 3-week postdischarge appointment. Approximately 5 months after discharge, the patient was re-treated by the cardiologist with enoxaparin 110 mg twice daily for 3 days to bridge to warfarin after he developed a deep vein thrombosis while taking apixaban. He did not develop hemorrhagic bullae upon retreatment with enoxaparin.
Heparin-induced hemorrhagic bullous dermatosis (HBD) has been associated with administration of both unfractionated and low-molecular-weight heparin.1 The condition typically develops 5 to 21 days after initiation of heparin as asymptomatic, purple-to-black bullae, sometimes with an erythematous halo.2,3 The arms and legs are the most common location, but the exact pathogenesis of the lesions remains unknown.3,4 Most cases resolve within weeks of discontinuing heparin, although some reports have suggested that discontinuation is unnecessary.3,4
Histopathologic analysis shows intraepidermal or subepidermal bullae with red blood cells and fibrin in the absence of vasculitis and intravascular thrombi.1,4 Immunofluorescence studies are negative.3 In a comprehensive review of HBD, the investigators hypothesized that the pathogenesis may be related to noninflammatory to pauci-inflammatory activation of basement membrane zone proteases or possibly epithelial or endothelial fragility in conjunction with trauma that causes disruption of the vascular endothelium (eg, subcutaneous injections, vasculitis).4
Our case is of particular interest because the bullae were strikingly limited to sites of subcutaneous injection and surrounding areas along with coexistent endothelial pathology on the lower legs (capillaritis and pitting edema). These clinical observations support trauma from the injections and altered endothelia as pathogenetic factors in HBD.
Of interest, our patient had 2 prior hospitalizations during which he received prophylactic enoxaparin and did not develop hemorrhagic bullae. Furthermore, repeat exposure to therapeutic dosing of enoxaparin with a shorter duration did not result in recurrence of HBD. This suggests that heparin dosing and duration of therapy also might be involved in the development of HBD.
Our hope is that future reports of HBD will address the presence or absence of coexistent cutaneous pathology, such as edema, stasis dermatitis, bruising, and capillaritis, along with heparin dosing, duration, and prior exposure to heparin treatment so that risk factors and pathogenesis can be further investigated. We also agree with Snow et al4 that HBD should be included as an outcome in future trials of heparin therapy.
- Komforti MK, Bressler ES, Selim MA, et al. A rare cutaneous manifestation of hemorrhagic bullae to low-molecular-weight heparin and fondaparinux: report of two cases: letter to the editor. J Cutan Pathol. 2017;44:104-106. doi:10.1111/cup.12821
- Peña ZG, Suszko JW, Morrison LH. Hemorrhagic bullae in a 73-year-old man. JAMA Dermatol. 2013;149:871-872. doi:10.1001/jamadermatol.2013.3364a
- Gouveia AI, Lopes L, Soares-Almeida L, et al. Bullous hemorrhagic dermatosis induced by enoxaparin. Cutan Ocul Toxicol. 2016;35:160-162. doi:10.3109/15569527.2015.1041033
- Snow SC, Pearson DR, Fathi R, et al. Heparin‐induced haemorrhagic bullous dermatosis. Clin Exp Dermatol. 2018;43:393-398. doi:10.1111/ced.13327
- Komforti MK, Bressler ES, Selim MA, et al. A rare cutaneous manifestation of hemorrhagic bullae to low-molecular-weight heparin and fondaparinux: report of two cases: letter to the editor. J Cutan Pathol. 2017;44:104-106. doi:10.1111/cup.12821
- Peña ZG, Suszko JW, Morrison LH. Hemorrhagic bullae in a 73-year-old man. JAMA Dermatol. 2013;149:871-872. doi:10.1001/jamadermatol.2013.3364a
- Gouveia AI, Lopes L, Soares-Almeida L, et al. Bullous hemorrhagic dermatosis induced by enoxaparin. Cutan Ocul Toxicol. 2016;35:160-162. doi:10.3109/15569527.2015.1041033
- Snow SC, Pearson DR, Fathi R, et al. Heparin‐induced haemorrhagic bullous dermatosis. Clin Exp Dermatol. 2018;43:393-398. doi:10.1111/ced.13327