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Genes, Chromosomes & Cancer Sep 2022Tumors with NUTM1 fusions occur predominantly in the thoracic cavity and head and neck region. However, recent literature expanded the location of NUTM1-translocated...
NUTM1-fusion positive malignant neoplasms of the genitourinary tract: A report of six cases highlighting involvement of unusual anatomic locations and histologic heterogeneity.
Tumors with NUTM1 fusions occur predominantly in the thoracic cavity and head and neck region. However, recent literature expanded the location of NUTM1-translocated malignancy to soft tissue, brain, and visceral organs. In this study, we describe the first series of six NUTM1-translocated carcinomas and sarcomas occurring in the genitourinary tract. The sites of origin were kidney (n = 2), bladder (n = 3), and penis (n = 1). All tumors occurred in adulthood (range: 30-78 years). The histologic features were heterogeneous, showing epithelial, spindle cell, or primitive small blue round cell morphology. Glandular architecture, keratinization, rhabdoid cells, or myxoid-to-edematous stromal component were also noted. In three cases, features were in keeping with a carcinoma (two from kidney and one from bladder), whereas the remaining three were classified as malignant undifferentiated neoplasm (MUN)/sarcoma. Fusion partners detected in four cases tested by either FISH and/or RNA sequencing were BRD4 in two kidney tumors, MXD1 in a bladder sarcoma, and MXD4 in a penile sarcoma. NUT immunostain showed diffuse spiculated positivity in five cases. Immunopositivity for various cytokeratins was noted in two tumors. The outcome of NUTM1-rearranged genitourinary malignancy was dismal: four of five cases with follow-up developed distant metastasis, and three suffered disease-specific death. In conclusion, NUTM1-rearranged carcinoma and sarcoma can affect the genitourinary tract, including kidney, bladder, and penis. Histologic features and keratin immunoexpression are highly variable. A NUTM1-fusion positive malignancy may be included in the differential diagnosis of a MUN of the genitourinary tract given the dismal outcome and the existing BET-targeted therapy for tumors with BRD3/4::NUTM1 fusion.
Topics: Adult; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biomarkers, Tumor; Carcinoma; Cell Cycle Proteins; Humans; Male; Neoplasm Proteins; Nuclear Proteins; Oncogene Proteins, Fusion; Repressor Proteins; Sarcoma; Soft Tissue Neoplasms; Transcription Factors
PubMed: 35430756
DOI: 10.1002/gcc.23046 -
Cancer Jun 2013Population-based studies comprehensively describing incidence patterns of human papillomavirus (HPV)-related preinvasive and invasive neoplasms prior to widespread HPV...
BACKGROUND
Population-based studies comprehensively describing incidence patterns of human papillomavirus (HPV)-related preinvasive and invasive neoplasms prior to widespread HPV vaccination are sparse.
METHODS
Age-adjusted incidence rates (IRs), IR ratios (IRRs), and annual percent changes (APCs) in IRs were calculated for potentially HPV-related tumors diagnosed in the Surveillance, Epidemiology and End Results (SEER) Program during 1978 through 2007.
RESULTS
Overall IRs for preinvasive tumors were significantly higher than for invasive squamous cell tumors of cervix (IRR = 3.42), vulva (IRR = 1.87), and vagina (IRR = 1.19) and significantly lower for adenomatous cervical tumors (IRR = 0.43), and squamous cell tumors of penis (IRR = 0.64), anus (males, IRR = 0.53; females, IRR = 0.14), and head and neck (H&N) (males, IRR = 0.01; females, IRR = 0.02). Incidence of preinvasive squamous tumors of cervix, vagina, and penis rose rapidly over time and decreased for invasive neoplasms. The most rapid increases occurred for preinvasive (males, APC = 16.0; females, APC = 7.3) and invasive anal tumors (males, APC = 3.6; females, APC = 2.3). IR patterns were generally similar among evaluable racial/ethnic groups, with the exception of H&N invasive tumor IRs which increased exclusively among white males.
CONCLUSIONS
Contrary to the opposing trends of preinvasive and invasive squamous tumors of cervix, vagina, and penis, preinvasive and invasive anal tumor IRs increased significantly over time by sex, age, and racial/ethnic groups. Successful HPV vaccination programs are needed to measurably reduce incidence of HPV-related neoplasms in the future, particularly for cancer sites with rising incidence rates for which effective screening modalities are limited. Cancer 2013;119:2291-2299. © 2013 American Cancer Society.
Topics: Adolescent; Adult; Aged; Anus Neoplasms; Carcinoma, Squamous Cell; Female; Humans; Male; Middle Aged; Papillomavirus Infections; Penile Neoplasms; SEER Program; United States; Uterine Cervical Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms; Young Adult
PubMed: 23580435
DOI: 10.1002/cncr.27989 -
European Journal of Cancer (Oxford,... Jan 2001To assess the prognostic factors and the outcome in patients with squamous-cell carcinoma of the penis, a retrospective review of 41 consecutive patients with...
To assess the prognostic factors and the outcome in patients with squamous-cell carcinoma of the penis, a retrospective review of 41 consecutive patients with non-metastatic invasive carcinoma of the penis, treated between 1962 and 1994, was performed. The median age was 59 years (range: 35-76 years). According to the International Union Against Cancer (UICC) 1997 classification, there were 12 (29%) T1, 24 (59%) T2, 4 (10%) T3 and 1 TX (2%) tumours. The N-classification was distributed as follows: 29 (71%) patients with N0, 8 (20%) with N1, 3 (7%) with N2 and 1 (2%) with N3. Forty-four per cent (n=18) of the patients underwent surgery: partial penectomy with (n=4) or without (n=12) lymph node dissection, or total penectomy with (n=1) or without (n=1) lymph node dissection. 23 patients were treated with radiation therapy alone, and all but 4 of the patients who were operated upon received postoperative radiation therapy (n=14). The median follow-up period was 70 months (range 20-331 months). In a median period of 12 months (range 5-139 months), 63% (n=26) of the patients relapsed (local in 18, locoregional in 2, regional in 3 and distant in 3). Local failure (stump in the operated patients, and the tumour bed in those treated with primary radiation therapy) was observed in 4 out of 16 (25%) patients treated with partial penectomy +/-postoperative radiotherapy versus 14 out of 23 (61%) treated with primary radiotherapy (P=0.06). 15 (83%) out of 18 local failures were successfully salvaged with surgery. In all patients, 5- and 10-year survival rates were 57% (95% confidence interval (CI), 41-73%) and 38% (95% CI, 21-55%), respectively. The 5-year local and locoregional rates were 57% (95% CI, 41-73%) and 48% (95% CI, 32-64%), respectively. In patients treated with primary radiotherapy, 5- and 10-year probabilities of surviving with penis preservation were 36% (95% CI, 22-50%) and 18% (95% CI, 2-34%), respectively. In multivariate analyses, survival was significantly influenced by the N-classification, and surgery was the only independent factor predicting the locoregional control. We conclude that, in patients with squamous-cell carcinoma of the penis, local control is better in patients treated with surgery. However, there seems to be no difference in terms of survival between patients treated by surgery and those treated by primary radiotherapy +/-salvage surgery, with 39% having organ preservation.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Combined Modality Therapy; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Penile Neoplasms; Retrospective Studies; Survival Analysis; Treatment Outcome
PubMed: 11166146
DOI: 10.1016/s0959-8049(00)00368-3 -
Nature Communications May 2020Penile squamous cell carcinoma (PSCC) accounts for over 95% of penile malignancies and causes significant mortality and morbidity in developing countries. Molecular...
Penile squamous cell carcinoma (PSCC) accounts for over 95% of penile malignancies and causes significant mortality and morbidity in developing countries. Molecular mechanisms and therapies of PSCC are understudied, owing to scarcity of laboratory models. Herein, we describe a genetically engineered mouse model of PSCC, by co-deletion of Smad4 and Apc in the androgen-responsive epithelium of the penis. Mouse PSCC fosters an immunosuppressive microenvironment with myeloid-derived suppressor cells (MDSCs) as a dominant population. Preclinical trials in the model demonstrate synergistic efficacy of immune checkpoint blockade with the MDSC-diminishing drugs cabozantinib or celecoxib. A critical clinical problem of PSCC is chemoresistance to cisplatin, which is induced by Pten deficiency on the backdrop of Smad4/Apc co-deletion. Drug screen studies informed by targeted proteomics identify a few potential therapeutic strategies for PSCC. Our studies have established what we believe to be essential resources for studying PSCC biology and developing therapeutic strategies.
Topics: Animals; Carcinoma, Squamous Cell; Cell Line; Cisplatin; Humans; Immunohistochemistry; Immunotherapy; Male; Mice; Mice, Inbred C57BL; Myeloid Cells; Myeloid-Derived Suppressor Cells; Penile Neoplasms; Proteomics; SOXB1 Transcription Factors; Tissue Array Analysis; Transcriptome
PubMed: 32358507
DOI: 10.1038/s41467-020-15980-9 -
Virchows Archiv : An International... Jun 2022Penile squamous cell carcinomas are rare tumor entities throughout Europe. Early lymphonodal spread urges for aggressive therapeutic approaches in advanced tumor stages....
Penile squamous cell carcinomas are rare tumor entities throughout Europe. Early lymphonodal spread urges for aggressive therapeutic approaches in advanced tumor stages. Therefore, understanding tumor biology and its microenvironment and correlation with known survival data is of substantial interest in order to establish treatment strategies adapted to the individual patient. Fifty-five therapy naïve squamous cell carcinomas, age range between 41 and 85 years with known clinicopathological data, were investigated with the use of tissue microarrays (TMA) regarding the tumor-associated immune cell infiltrate density (ICID). Slides were stained with antibodies against CD3, CD8 and CD20. An image analysis software was applied for evaluation. Data were correlated with clinicopathological characteristics and overall survival. There was a significant increase of ICID in squamous cell carcinomas of the penis in relation to tumor adjacent physiological tissue. Higher CD3-positive ICID was significantly associated with lower tumor stage in our cohort. The ICID was not associated with overall survival. Our data sharpens the view on tumor-associated immune cell infiltrate in penile squamous cell carcinomas with an unbiased digital and automated cell count. Further investigations on the immune cell infiltrate and its prognostic and possible therapeutic impact are needed.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Count; Europe; Humans; Male; Middle Aged; Penile Neoplasms; Tumor Microenvironment
PubMed: 35024940
DOI: 10.1007/s00428-022-03271-1 -
British Medical Journal Jan 1948
Topics: Humans; Male; Penile Neoplasms; Penis
PubMed: 18932878
DOI: 10.1136/bmj.1.4541.122-e -
Asian Journal of Surgery Apr 2007We analysed the results of penis-preserving (conservative) treatment of early stage cancer of the penis with neodymium: yttrium-aluminium-garnet (Nd:YAG) laser with...
INTRODUCTION
We analysed the results of penis-preserving (conservative) treatment of early stage cancer of the penis with neodymium: yttrium-aluminium-garnet (Nd:YAG) laser with long-term follow-up in a developing country.
METHODS
This was a retrospective study of 32 patients with cancer penis from 1993 to 2005 who were treated by Nd:YAG laser local excision and in situ coagulation of the tumour bed.
RESULTS
Out of 32 patients who were treated with Nd:YAG laser, 25 had (p)T(1) and seven had (p)T(2) stage cancer penis. The median follow-up was 70 months (range, 6-120 months). Two had stopped attending the follow-up clinic after 6-12 months. Three patients had concurrent and six had delayed inguinal block dissection. There was no mortality but two (6.25%) patients developed recurrence in 48-60 months post laser excision. Penis was preserved in all 32 patients. All patients were satisfied with the cosmetic result. Eight patients practiced celibacy, in 23 sexual functions were normal and in one this information was not available. Micturition was in standing posture in all 32 patients.
CONCLUSION
The result of this study shows that Nd:YAG laser treatment of early stage cancer penis has good local control with preservation of the penis.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Humans; Laser Therapy; Male; Middle Aged; Penile Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 17475583
DOI: 10.1016/S1015-9584(09)60145-7 -
The Journal of Urology Jul 1992Metastatic cancer to the penis is rare, its optimum treatment remains poorly defined and the outcome of patients with such metastases is poor. Hyperthermia in... (Review)
Review
Metastatic cancer to the penis is rare, its optimum treatment remains poorly defined and the outcome of patients with such metastases is poor. Hyperthermia in conjunction with radiation therapy has been shown to be an effective modality in the treatment of locally advanced or recurrent cancer and hyperthermia alone is under evaluation in treating benign disorders, such as hypertrophy of the prostate. Recently, 4 patients with symptomatic metastatic lesions to the penis (3 had primary prostatic cancer and 1 had rectal cancer) were treated with radiation therapy and hyperthermia. Treatment was well tolerated except for pain during hyperthermia, which limited the temperatures that could be obtained. All of the patients improved symptomatically, 1 achieved a complete response and 2 had partial responses. No significant complications were noted. Symptomatic control was maintained in all patients for the duration of their survival. This limited series suggests the possible role of local hyperthermia as an adjunct to radiation therapy in the treatment of metastases to the penis.
Topics: Adenocarcinoma; Combined Modality Therapy; Humans; Hyperthermia, Induced; Male; Penile Neoplasms; Prostatic Neoplasms; Rectal Neoplasms
PubMed: 1613885
DOI: 10.1016/s0022-5347(17)36512-6 -
Cancer Control : Journal of the Moffitt... 2002Cancer of the penis is an uncommon malignancy in developed countries, but the incidence is as high as 17% of all male cancers in some undeveloped countries. The surgical... (Review)
Review
BACKGROUND
Cancer of the penis is an uncommon malignancy in developed countries, but the incidence is as high as 17% of all male cancers in some undeveloped countries. The surgical management of this disease has improved due to better knowledge of risk for metastasis and newer imaging technologies to assess the regional lymph nodes.
METHODS
We review the literature on incidence, etiology, pathology, clinical presentation, staging, and management of penile cancer. We present our institutional experience with 160 patients who underwent extended ilioinguinal lymph node dissection, as well as with 7 patients who underwent a modified lymph node dissection.
RESULTS
Better understanding of pathologic features allow for stratification of patients into low, intermediate, or high risk for lymph node involvement. Lymphatic mapping to this stratification improves selection of patients who might benefit from lymph node dissection after excision of the primary lesion. Our experience with lymph node dissection yielded a high incidence of positive lymph nodes when lymphadenopathy was present. The recent use of a modified lymph node dissection has minimized morbidity. Current chemotherapy agents are ineffective in this disease.
CONCLUSIONS
Pathologic features of the primary lesion and the incorporation of lymphatic mapping have improved the selection of patients who might benefit from lymph node dissection. The use of a modified lymph node dissection in selected patients has decreased morbidity. Effective chemotherapy agents are needed in the management of advanced penile cancer.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Humans; Lymph Nodes; Male; Middle Aged; Neoplasm Staging; Penile Neoplasms; Radionuclide Imaging; Sentinel Lymph Node Biopsy; Urologic Surgical Procedures, Male
PubMed: 12228756
DOI: 10.1177/107327480200900405 -
Diagnostic Pathology Oct 2023Invasive stratified mucin-producing carcinoma is a recently recognized adenocarcinoma with distinctive features. It was first described in the cervix but similar tumors...
BACKGROUND
Invasive stratified mucin-producing carcinoma is a recently recognized adenocarcinoma with distinctive features. It was first described in the cervix but similar tumors have since been reported in the penis, anus and prostate. In the gastrointestinal tract, the phenomenon of epithelial stratification has an interesting embryologic morphogenesis. Gastrointestinal mucosa starts off as nascent columnar epithelium that is subsequently patterned to confer regional specific functions. However, in disease states, normal architectural patterning can be disrupted by aberrant differentiation. Given this background and the phenotypic plasticity of neoplastic cells, we were interested in ascertaining whether invasive stratified mucin-producing carcinoma occurs in the colorectum.
METHODS
This was a retrospective study of all 584 cases of colorectal carcinoma accessioned at our institution over a 2-year period (January 2021- December 2022). Cases were analyzed to determine which fulfilled the criteria for invasive stratified mucin-producing carcinoma.
RESULTS
There were 9 cases of colorectal invasive stratified mucin-producing carcinoma-one pure form and 8 mixed. They showed the classic colorectal (CK20 + , CDX2 + , CK7-) immunostaining profile but, based on various morphologic criteria, they could be distinguished from conventional adenocarcinoma NOS, mucinous, signet ring cell, medullary, goblet cell and undifferentiated carcinomas. About half the cases were MLH1/PMS2 deficient and BRAF &/or PIK3CA mutated, which aligns with the hypermutated phenotype.
CONCLUSIONS
Colorectal invasive stratified mucin-producing carcinoma appears to be a real entity, best recognized in its early stages. It appears to be a high-grade carcinoma. With tumor progression, it evolves into a mucinous adenocarcinoma with a proclivity towards signet ring cells. In summary, the study of this tumor, particularly in its early stages, provides useful clues to further understanding the biology and progression of large bowel cancer. Further studies are required to learn more about this tumor.
Topics: Male; Female; Humans; Retrospective Studies; Colorectal Neoplasms; Adenocarcinoma; Colonic Neoplasms; Adenocarcinoma, Mucinous; Mucins
PubMed: 37853375
DOI: 10.1186/s13000-023-01396-8