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In JoVE (1)
Other Publications (18)
- The American Journal of Surgical Pathology
- The American Journal of Surgical Pathology
- International Journal of Leprosy and Other Mycobacterial Diseases : Official Organ of the International Leprosy Association
- The American Journal of Surgical Pathology
- International Journal of Surgical Pathology
- The American Journal of Surgical Pathology
- Biomédica : Revista Del Instituto Nacional De Salud
- Journal of Industrial Microbiology & Biotechnology
- Parasitology Research
- The American Journal of Surgical Pathology
- The American Journal of Surgical Pathology
- The American Journal of Tropical Medicine and Hygiene
- The American Journal of Surgical Pathology
- Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
- The American Journal of Surgical Pathology
- Histopathology
- World Journal of Urology
- Human Pathology
Articles by Ingrid Rodriguez in JoVE
JoVE Clinical and Translational Medicine
Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease
1Department of Pharmacology, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, 2Department of Emergency and Intensive Care, ProMedica Sponsored Research
Spectral Karyotyping (SKY) is an advanced cytogenetics technique to identify genomic and chromosomal aberrations. This technique takes advantage of chromosome painting probes, which allow classification of all chromosomes. SKY can also identify complex chromosome aberrations and segregation defects in mice and humans with various diseases, including polycystic kidney disease.
Other articles by Ingrid Rodriguez on PubMed
Mucinous Tumors of the Ovary: a Clinicopathologic Analysis of 75 Borderline Tumors (of Intestinal Type) and Carcinomas
With the exception of benign cystadenomas, mucinous ovarian tumors are rare and heterogeneous neoplasms. They have been classified as either borderline tumors or carcinomas for almost 30 years. Subsequently, the borderline tumors have been subclassified into endocervical-like and intestinal types. The diagnostic criteria for distinguishing borderline tumors of the intestinal type from mucinous carcinomas have varied, making difficult the interpretation of prognostic information. More recently, a further subdivision of the former tumors into forms with only epithelial atypia and variants with focal intraepithelial carcinoma has been proposed. Consequently, in this study of 41 mucinous borderline tumors of intestinal type and 34 mucinous carcinomas, the former were also subdivided into 30 cases with mild to moderate atypia only and 11 with areas of intraepithelial carcinoma. All 30 purely borderline tumors were stage I tumors, and all 15 with follow-up information (including one case with microinvasion) were clinically benign. All 11 mucinous borderline tumors that had foci of intraepithelial carcinoma were also stage I neoplasms, and none of the eight patients with follow-up data (including one with microinvasive carcinoma) recurred. Thirty-four invasive carcinomas were subclassified into 15 expansile and 19 infiltrative subtypes. All 15 carcinomas with only expansile invasion were stage I; none of the 11 with follow-up data recurred. Three of nine patients with stage I infiltrative carcinomas with follow-up information had a fatal recurrence. Eight of the remaining 10 infiltrative carcinomas had extended beyond the ovary at the time of diagnosis (stages II and III); of the six patients with follow-up data, four died of tumor and two were alive with disease. In stage I carcinomas nuclear grade and tumor rupture correlated with unfavorable prognosis, but less than infiltrative invasion. However, all three fatal tumors were infiltrative carcinomas that had ruptured, and two contained grade 3 malignant nuclei. Combination of infiltrative invasion, high nuclear grade, and tumor rupture is a strong predictor of recurrence for stage I mucinous ovarian tumors. Among the 19 infiltrative tumors, 13 contained foci of anaplastic carcinoma. Of the seven patients with stage I tumors and follow-up data, only one patient whose tumor had ruptured intraoperatively had a fatal recurrence. The presence of anaplastic components in stage Ia (intact) carcinomas did not have an adverse effect in their outcome, even when the undifferentiated carcinomatous elements appeared in the form of mural nodules.
Sarcoma-like Mural Nodules in Mucinous Cystic Tumors of the Ovary Revisited: a Clinicopathologic Analysis of 10 Additional Cases
Ten mucinous cystic ovarian tumors that contained sarcoma-like mural nodules are described. The nodules were studied by conventional and immunohistochemical methods. The sarcoma-like mural nodules occurred predominantly in middle-aged women, were multiple and sharply demarcated from the adjacent mucinous tumor, had small size, and exhibited a heterogeneous cell population. Distinction of these lesions from true sarcomatous nodules and foci of anaplastic carcinoma is important because of the worse prognosis of the two latter tumors compared with the favorable behavior of the sarcoma-like mural nodules. Six of the eight patients with follow-up information were alive and clinically free of recurrence at a mean follow-up interval of 12 years. Two patients died of other causes (thyroid and breast carcinomas). The nature of the nodules is not clear. Sarcoma-like mural nodules probably represent a reactive and self-limited phenomenon within a neoplasia. Their coexpression of vimentin and cytokeratins is consistent with an origin from submesothelial mesenchymal cells, which undergo partial transformation into epithelial cells.
Gelatinase Activity in Mycobacterium Bovis Protein Extract
Proteases are well-recognized as virulence factors in different pathologies, resulting in tissue damage potential. Despite efforts over the past few years to identify mycobacterial protein antigens, there is little information regarding the role of mycobacterial proteinase activities. In this study, by zymography techniques, we have detected and partially studied some biochemical properties of Mycobacterium bovis proteases, such as pH dependency of activity and susceptibility to classical proteinase inhibitors. We observed optimal proteolytic activity at pH 8. Some proteinases were inhibited by classic inhibitors of serine proteases, such as PMSF, AEBSF, and 3-4 DCI. In some AEBSF pre-treated preparations we observed residual gelatinase activity in Rf 0.32. This gelatinase was stimulated by Zn2+ and inhibited by OPA (1 mM). This last effect was reversed by exposure to equimolar quantitative OPA/Zn+2 (1 mM/1 mM). These results suggest the existence of serine proteinase and metalloproteinase types in protein extracts of Mycobacterium bovis.
Malignant Mesonephric Tumors of the Female Genital Tract: a Clinicopathologic Study of 9 Cases
Nine malignant mesonephric tumors were obtained from the consultation files of one of the authors (J.P.) over a 13-year period (1988-2001). There were 4 adenocarcinomas (ACs) and 5 malignant mixed mesonephric tumors (MMMTs). The ACs were found in the cervix (3) and vagina (1). The MMMTs involved the uterus (1), cervix (3), and vagina (1). Most patients presented with abnormal vaginal bleeding. The 4 patients with mesonephric AC ranged in age from 24 to 54 years (mean, 41 years). The tumors measured 2 to 6 cm (mean, 3.7 cm). Two ACs were stage I and two were stage II. Two of the three patients with follow-up information were alive without clinical evidence of disease at 3 and 11.5 years, and the other was alive with recurrent tumor 8.5 years postoperatively. The 5 patients with MMMTs ranged in age from 37 to 62 years (mean, 49 years). The mean size of four tumors was 5.2 cm (range, 3.5-8 cm). The uterine MMMT infiltrated the entire myometrial wall extending to the endometrial cavity where it resembled an endometrial polyp. Although the most common histologic pattern in the current series was the glandular (ductal) pattern, retiform, tubular, and solid growth patterns were also encountered. Among the MMMT subgroup, the sarcomatous component was homologous in 3 cases (endometrial stromal or spindle cell) and heterologous in the other 2 cases (skeletal muscle and cartilage). Of the 4 patients with follow-up information available, 1 (stage II) died of disease 7 months after surgery, another (stage IV) was alive with bone metastases at 3.3 years, and the other 2 patients (stages IB and IC) had no clinical evidence of disease at 1 and 3.7 years, respectively. Evidence of mesonephric hyperplasia was found in 5 (42%) cases. The MMMT that arose in the corpus presented as an endometrial polyp. In this case, histologic differential diagnosis includes serous carcinoma, endometrial stromal sarcoma, and uterine tumor resembling ovarian sex cord-stromal tumor. Immunostainings are not helpful. Mesonephric ACs often present in early stage and have better prognosis than their müllerian counterparts. Surgery alone appears to be the treatment of choice. In contrast, MMMTs may present in advanced stage and are aggressive tumors, similar to malignant mixed müllerian tumors.
Limitations in the Interpretation of Biopsies in Patients with Penile Squamous Cell Carcinoma
Surgeons often perform small or superficial penile biopsies that are difficult to classify definitely with regard to a benign or malignant nature, and if malignant, cannot always be accurately subclassified. Staging and therapeutic decisions rely on the identification, in these materials, of pathologic parameters related to prognosis. In this study, we evaluated the accuracy and completeness of pathologic information obtained from biopsies of 57 consecutive patients with squamous cell carcinoma (SSC) of the penis, and compared it with the information obtained from penectomies. Diagnostic accuracy was determined by recording discordances of critical factors in biopsies and penectomies. The evaluated parameters were as follows: cancer diagnosis, histologic type, tumor grade, depth of invasion (anatomical levels), and vascular invasion. Histologic subtypes of SCC were the following: usual 37, verruciform 11, mixed 7, pseudohyperplastic 1, and sarcomatoid 1. Grades were 1, 2, and 3 (well, moderately and poorly differentiated). Levels of invasion were lamina propria, corpus spongiosum, and corpus cavernosum in the glans; and lamina propria, dartos, and skin in the foreskin. In 2 patients with well-differentiated tumors a diagnosis of cancer could not be established in biopsy material. In 17 cases (30%) there was a biopsy-penectomy discordance of histologic types, especially of verruciform and mixed carcinomas. Biopsies failed to identify the correct histologic grade in 30% of the cases. A higher grade was usually identified in penectomy specimens. Because biopsies were superficial, the deepest point of invasion could not be determined in 91% of the cases. Vascular invasion was identified in biopsies in only 1 of 8 patients. In summary, biopsies were useful for cancer diagnosis except in 2 differentiated variants of penile squamous cell carcinoma. However, important pathologic parameters related to prognosis were missed on biopsy materials, and they were more accurately evaluated in penectomy specimens. We conclude that clinical and pathologic staging of penile cancer, at least in our material, cannot depend on biopsy information alone. Data from biopsies may be insufficient to make a decision whether to perform a groin dissection, or for prognostic evaluation in those patients in whom other treatment modalities (such as radiotherapy or chemotherapy) are being considered.
Endocervical-like Mucinous Borderline Tumors of the Ovary: a Clinicopathologic Analysis of 31 Cases
Ovarian mucinous borderline tumors are divided into two morphologic groups: endocervical-like and intestinal type, the latter comprising the majority of cases. Thirty-one endocervical-like ovarian mucinous borderline tumors (ELMBTs) were reviewed and evaluated for the presence of intraepithelial carcinoma and microinvasion. Intraepithelial carcinoma was identified in 13% and stromal microinvasion in 23% of cases. All but 1 patient were stage I. Follow-up information was available for 21 patients; all were alive with no evidence of disease at a mean follow-up interval of 5.7 years. Six of 8 patients with ELMBT containing foci of microinvasion and/or intraepithelial carcinoma and for whom follow-up was available were alive with no evidence of disease at a mean follow-up interval of 6.6 years. These results indicate that ELMBTs, specifically those exhibiting intraepithelial carcinoma and microinvasion, are tumors associated with an excellent prognosis. The frequency of occurrence and criteria for the diagnosis of intraepithelial carcinoma and microinvasion in ELMBT are discussed.
[Trypanosoma Rangeli Parasite-vector-vertebrate Interactions and Their Relationship to the Systematics and Epidemiology of American Trypanosomiasis]
Trypanosoma rangeli is a species of trypanosome second to T. cruzi, that is infective to humans in Latin America. Variability in the biological, biochemical and molecular characteristics between different isolates isolates of this parasite have been recorded.
Characterization of Kinetic Parameters and the Formation of Volatile Compounds During the Tequila Fermentation by Wild Yeasts Isolated from Agave Juice
The production of aroma compounds during tequila fermentation using four native yeast strains isolated from agave juice was quantified at controlled (35 degrees C) and uncontrolled temperatures (room temperature) by gas chromatography (FID). Three of the four strains were identified as Saccharomyces cerevisiae (MTLI 1, MALI 1 and MGLI 1) and one as Kloeckera apiculata (MALI 2). Among the aroma compounds produced, acetaldehyde has the highest accumulation at the controlled temperature and before 50% of sugar was consumed. The S. cerevisiae strains produced ethyl acetate in almost the same quantity at a concentration of 5 mg/L and the K. apiculata produced six-times more (30 mg/L) than the S. cerevisiae strains, independent of the fermentation temperature. The rate and amount of 1-propanol, amyl alcohols and isobutanol production were affected by the type of yeast used. The K. apiculate strain produced 50% less of the higher alcohols than the Saccharomyces strains. The results obtained showed that indigenous isolated yeasts play an important role in the tequila flavor and suggest that mixtures of these yeasts may be used to produce tequila with a unique and desirable aroma.
Geographical Clustering of Trypanosoma Cruzi I Groups from Colombia Revealed by Low-stringency Single Specific Primer-PCR of the Intergenic Regions of Spliced-leader Genes
A low-stringency single-primer polymerase chain reaction (LSSP-PCR) typing procedure targeted to the intergenic regions of spliced-leader genes (SL) was designed to profile Trypanosoma cruzi I stocks from endemic regions of Colombia. Comparison between SL-LSSP-PCR profiles of parasite DNA from vector faeces and cultures isolated from those faeces showed more conservative signatures than profiles using LSSP-PCR targeted to the minicircle variable regions (kDNA). This was also observed by analysing 15 parasite clones from one stock as well as serial samples of a same stock after in vitro culturing or inoculation into mice. Thus, SL-LSSP-PCR appears more appropriate than kDNA-LSSP-PCR for reliable typing of major T. cruzi I groups from in vitro cultured stocks and triatomine faeces. SL-LSSP-PCR grouped 46 of 47 T. cruzi I Colombian stocks according to their geographical procedences in four clusters: Cluster Cas from Casanare Department, Cluster Mg from Northern Magdalena department, Cluster Mom from Momposina Depression in Southern Magdalena and finally Cluster NW from northwestern Colombia, including Sucre, Chocó, Córdoba and Antioquia departments. Sequence analysis identified punctual mutations among amplicons from each cluster. Within Cluster Mg, sequence polymorphism allowed association with different sylvatic vector species. Novel SL sequences and LSSP-PCR profiles are reported from T. cruzi I infecting Eratyrus cuspidatus, Panstrongylus geniculatus and Rhodnius pallescens vectors.
The Prognostic Index: a Useful Pathologic Guide for Prediction of Nodal Metastases and Survival in Penile Squamous Cell Carcinoma
A concern of surgical oncologists has been to find a method to select patients for groin dissection in penile carcinomas considering the high morbidity of this procedure. A promising methodology, in the identification of early metastatic foci by the sentinel lymph node technique (initiated in Paraguay in the 1970s), was found, using a static anatomic approach, to be associated with a recurrence rate of 30%. Later, a dynamic method using radioactive tracers and peritumoral dye injection was introduced with an improvement in patients' outcome. Recurrences, however, remained high in most studies at a rate of about 15% to 20% except in few highly specialized centers with failure rates of 5%. The technical sophistication, lack of multicenter reproduction, and cost of dynamic sentinel node biopsies preclude their routine implementation in developing countries and other approaches are necessary. Because histologic grade, depth of tumor infiltration, and perineural invasion (PNI) are considered among the most important pathologic prognostic parameters in penile cancer, we devised a Prognostic Index combining these 3 factors. In this study, we are evaluating the incidence of nodal metastasis according to the Prognostic Index score. Pathologic materials from 193 patients with penectomy/circumcision and bilateral groin dissections for invasive squamous cell carcinoma were analyzed. The Prognostic Index (ranging from 2 to 7) consisted in the addition of numerical values given to histologic grade (1 to 3), deepest anatomic level involved by cancer (1 to 3), and presence of PNI (0 or 1). Histologic grades were defined as follows: grade 1, carcinomas with minimal to no atypias; grade 3, tumors showing any proportion of anaplastic cells; and grade 2, the remainder tumors. The anatomic levels and their numerical values were: in glans, lamina propria, 1; corpus spongiosum, 2; and corpus cavernosum, 3. In foreskin they were: lamina propria, 1; dartos, 2; and skin, 3. PNI was evaluated as follows: absence of PNI, 0; presence of PNI, 1. Penile intraepithelial neoplasia (carcinoma in situ), or index 1, was excluded from the study. Mean follow-up obtained in all patients was of 81 months. The distribution of cases and rate of metastasis according to index scores were: 2 (1 case), no metastasis; 3 (17 cases), no metastasis; 4 (35 cases), 20% of metastasis; 5 50 cases), 50% of metastasis; 6 (47 cases), 66% of metastasis; and 7 (43 cases), 79% of metastasis. On logistic regression analysis evaluating various pathologic factors, Prognostic Index scores were found as the best predictors of inguinal node metastasis and patients' survival. Inguinal node dissections might not be necessary for patients with low indices (2 and 3). Nodal dissections might be formally indicated for high-grade indexes (5 to 7). Patients with index 4 should be individually assessed for nodal dissection. If sentinel node biopsy cannot be performed for various reasons the Prognostic Index might represent a useful pathologic guide to the clinicians in the often difficult decision to perform an inguinal dissection or not.
Histologic Grade in Penile Squamous Cell Carcinoma: Visual Estimation Versus Digital Measurement of Proportions of Grades, Adverse Prognosis with Any Proportion of Grade 3 and Correlation of a Gleason-like System with Nodal Metastasis
Histologic grade has been reported as an important pathologic parameter predictive of nodal metastases and outcome in patients with penile squamous cell carcinoma. There is no consensus about the criteria for grading and the proportion of anaplastic cells required to classify a tumor as high grade. The incidence and management of heterogeneous tumors (tumors harboring more than 1 histologic grade) are not well established. The purposes of this study were to present a grading model for penile cancer, to test the practicality of the system by comparing a visual ("naked-eye") estimation of the proportions of grades with a digitally guided measuring system and to determine the influence on nodal metastasis of the various proportions of grades. A total of 117 penectomy and circumcision specimens with bilateral inguinal lymph node dissections were studied and 62 heterogeneous tumors were identified (53%). The following steps were taken: (1) design of a grading system model; (2) determination of proportions of histologic grades by naked-eye evaluation and by digital measurement; (3) evaluation of metastasis according to proportions of grades; (4) determination of the influence of site of grade 3 in nodal metastasis; (5) design of a Gleason-like scoring system; and (6) statistical evaluation. We designed a 3-tier grading system. Grade 1: well-differentiated cells, almost undistinguishable from normal squamous cells except for the presence of minimal basal/parabasal cell atypia. Grade 3: tumors predominantly composed of anaplastic cells. Grade 2: all tumors not fitting into criteria described for grade 1 or 3. A visual and digital-based (slides scanned and the corresponding areas measured with an image-editing software) proportions of grades were estimated and the metastatic rate between them were confronted using different proportions of grade 3. To evaluate the influence of site of grade 3 on nodal metastasis, we selected 20 heterogeneous tumors. We established 3 sites: superficial, at or within the main tumor and deep at front of invasion. There was no significant difference between the visual estimation and the digital measurement systems. Heterogeneous tumors comprised about half of penile squamous cell carcinomas. The majority of the heterogeneous tumors were composed of a combination of grades 2 and 3 (68%). No statistical differences were noted in the incidence of nodal metastasis when comparing tumors with various proportions of anaplastic cells (P>0.10 in all cases). Metastatic rate was significantly more frequent in tumors harboring any proportion of grade 3 as compared with tumors without grade 3 (58% vs. 14%, P=0.04). Any proportion of grade 3 was equally associated with a significant risk of nodal metastasis. A Gleason-like system showed a correlation of higher scores and rate of nodal metastasis. No predictive advantage was found when comparing the Gleason-like model with the proposed 3-tier grading system. The proposed grading system emphasized both ends of the differentiation spectrum and was based on easily recognizable morphologic criteria. When histologically evaluating penile carcinomas, we recommend a careful search of areas of grade 3. Any focus of grade 3 should be sufficient to grade the neoplasm as a high-grade tumor.
Transmission Dynamics of Trypanosoma Cruzi Determined by Low-stringency Single Primer Polymerase Chain Reaction and Southern Blot Analyses in Four Indigenous Communities of the Sierra Nevada De Santa Marta, Colombia
This study attempted to evaluate the transmission dynamics of Trypanosoma cruzi in four indigenous communities of Sierra Nevada de Santa Marta (SNSM), Colombia. Low-stringency single primer-polymerase chain reaction (LSSP-PCR) of the minicircles and Southern blot analyses were used to characterize samples from patients, vectors, and reservoirs in these communities. The LSSP-PCR profiles revealed a high genetic variability but with similarities among the parasites present in the samples of vectors, patients, and reservoirs of the same and different communities. Cluster and analysis of molecular variance (AMOVA) analyses of data derived from LSSP-PCR and Southern blot suggest a gene flux among populations of T. cruzi circulating in patients, vectors, and reservoirs. The results support the idea that the domestic and wild transmission cycles overlap in the SNSM, with Rhodnius prolixus as the main vector and Triatoma dimidiata playing an important role in the transmission of Chagas disease in this zone, making the vector control strategy by spraying unsuccessful.
Papillary Squamous Cell Carcinoma, Not Otherwise Specified (NOS) of the Penis: Clinicopathologic Features, Differential Diagnosis, and Outcome of 35 Cases
There is a group of low-grade papillomatous squamous cell carcinomas (SCC) of the penis, collectively designated as "verruciform," that are difficult to classify. A proposal of classification grouped these tumors in warty (condylomatous), verrucous, and papillary carcinomas. Papillary SCC, not otherwise specified is the third distinctive type of penile low-grade verruciform neoplasms. We are presenting clinicopathologic features of 35 cases from 2 institutions. All specimens were penectomies or circumcisions. Mean age was 57 years. Sites of involvement were glans alone in 18 cases (51%), glans, coronal sulcus and foreskin in 13 cases (37%), glans and sulcus in 3 cases (9%), and foreskin in 1 case (3%). Papillary carcinomas were large (mean 5.6 cm) exophytic low-grade squamous neoplasms with hyperkeratosis and papillomatosis. Papillae were variable in length and shape. The tip was straight, undulated, spiky, or blunt. There was no koilocytosis. The interface between tumor and stroma was characteristically jagged and a moderate stromal reaction was evident in most cases. The majority of the tumors (94%) showed a low-grade histology with focally present poorly differentiated areas in 6% of the cases. The mean thickness of the tumor was 9.4 mm. The most commonly invaded anatomic levels were the corpus spongiosum and/or dartos (77% cases). Corpus cavernosum was invaded in 8 cases (23%). Vascular and perineural invasion were unusual. Frequent associated lesions were squamous hyperplasia, differentiated penile intraepithelial neoplasia, and lichen sclerosus (74%, 46%, and 34%, respectively). Nodal metastases were identified in 3 of 12 patients with bilateral groin dissections. Of the 20 patients followed, 18 were either with no evidence of disease (15 cases) or died from unrelated causes (3 cases). One patient was alive with evidence of systemic metastases and 1 died from disseminated penile cancer 32 months after original penectomy. In conclusion, papillary carcinomas were exophytic albeit, often deeply invasive low-grade neoplasms, with a low rate of nodal metastasis characterized by complex papillae, irregular fibrovascular cores, and jagged tumor base. Papillary SCC should be distinguished from other penile verruciform tumors, including verrucous and variants, warty and papillary basaloid carcinomas, and carcinoma cuniculatum. Helpful morphologic features for differential diagnosis are provided.
Warty-basaloid Carcinoma: Clinicopathological Features of a Distinctive Penile Neoplasm. Report of 45 Cases
Most penile cancers are squamous cell carcinomas, but there are several subtypes with different clinicopathologic, viral, and outcome features. We are presenting 45 cases of a distinctive morphological variant of penile squamous cell carcinoma composed of mixed features of warty and basaloid carcinomas. This tumor was earlier recognized in a recent viral study and showed a high association with human papillomavirus infection. However, clinicopathologic features are not well known. In this multi-institutional study, patients' mean age was 62 years. Most tumors (64%) invaded multiple anatomical compartments, including glans, coronal sulcus, and, especially, inner foreskin mucosa. Tumor size ranged from 2 to 12 cm (mean 5.5 cm). Three morphological patterns were recognized: (1) the most common, observed in two-thirds of the cases was that of a typical condylomatous tumor on surface and basaloid features in deep infiltrative nests; (2) in 15% of the cases, there were non-papillomatous invasive carcinoma nests with mixed basaloid and warty features; and (3) unusually, predominantly papillomatous. Invasion of penile erectile tissues was frequent, either corpus spongiosum or cavernosum (47% each). Tumors limited to lamina propria were rare. Most tumors were of high grade (89%). Vascular and perineural invasion were found in about one-half and one-quarter of cases, respectively. Associated penile intraepithelial neoplasia was identified in 19 cases and mostly showed basaloid, warty-basaloid, or warty features. Inguinal nodal metastases were found in 11/21 patients with groin dissections. Invasion of corpora cavernosa, high histological grade, and presence of vascular/perineural invasion were more prevalent in metastatic cases. In 21 patients followed, the cancer-specific mortality rate was 33% with a mean survival time of 2.8 years. Warty-basaloid carcinomas are morphologically distinctive human papillomavirus-related penile neoplasms that, such as basaloid carcinomas, are biologically more aggressive than typical warty carcinoma from which they should be distinguished.
Distinctive Immunohistochemical Profile of Penile Intraepithelial Lesions: a Study of 74 Cases
Several classification schemes for penile precancerous lesions have been proposed, but none of them seems to correlate with the current understanding of penile cancer pathogenesis. Recently, a system, which takes into account morphologic features and purported etiopathogenesis, was proposed, separating penile intraepithelial neoplasia (PeIN) in differentiated and warty/basaloid subtypes. This study was designed to seek an immunohistochemical profile that can be helpful in the classification and differential diagnosis of penile epithelial abnormalities and precancerous lesions using the aforementioned system. The immunohistochemical panel included stains for p16, p53, and Ki-67. For p16 immunostaining, only full-thickness positivity in all epithelial cells was considered as positive; for p53 and Ki-67 immunostaining, patchy or diffuse nuclear positivity above the basal layer was considered as positive. Seventy-four lesions in 59 patients were selected and classified as follows: differentiated PeIN, 34 cases; squamous hyperplasia (SH), 21 cases; basaloid PeIN, 15 cases; and warty PeIN, 4 cases. The mean age of patients was 64 years. Forty-two lesions (56.8%) were located in the glans and 32 (43.2%) in the foreskin. Overexpression of p16 was useful for distinguishing SH from warty/basaloid PeINs (0% vs. 94.7%, P<0.0001) but not SH from differentiated PeINs (0% vs. 5.9%, P=0.519). In addition, p16 allowed the distinction of differentiated and warty/basaloid PeINs (5.9% vs. 94.7%, P<0.0001). Immunohistochemistry results for p53 allowed the separation of SH and differentiated PeIN (9.5% vs. 44.1%, P=0.0078) and SH and warty/basaloid PeIN (9.5% vs. 55.6%, P=0.0042). Ki-67 immunostain was useful for distinguishing SH from differentiated PeIN (52.6% vs. 89.7%, P=0.0062) and SH from PeIN with warty and/or basaloid features (52.6% vs. 100%, P=0.0011). There seems to be a distinctive immunohistochemical profile for associated and precursor epithelial lesions of the penis. SH was p16 and p53 negative, with variable Ki-67 positivity. Differentiated PeIN was p16 negative and Ki-67 positive, with variable p53 positivity. Basaloid and warty PeINs were consistently p16 and Ki-67 positive, with variable p53 positivity. The use of a triple p16/p53/Ki-67 immunohistochemical panel was found to be helpful in the classification, differential diagnosis, and morphologic standardization of penile intraepithelial lesions.
Differentiated Precursor Lesions and Low-grade Variants of Squamous Cell Carcinomas Are Frequent Findings in Foreskins of Patients from a Region of High Penile Cancer Incidence
About 10-20% of all penile squamous cell carcinomas (SCCs) originate in the foreskin, but knowledge about preputial precursor and associated lesions is scant. The aims of the present study were to determine the prevalence of various precancerous and cancerous lesions exclusively affecting the foreskin, and to describe their pathological features.
Epidemiologic Profile, Sexual History, Pathologic Features, and Human Papillomavirus Status of 103 Patients with Penile Carcinoma
PURPOSE: The incidence of penile cancer is four times higher in Paraguay than in the United States or Europe. There are no adequate scientific explanations for this geographical variation. The goal of this study was to evaluate the interplay among risk factors, morphology of the primary tumor, and HPV status. METHODS: Information on socioeconomic status, education level, habits, and sexual history was obtained in 103 Paraguayan patients with penile cancer. All patients were then treated by surgery, and specimens were evaluated histopathologically. RESULTS: Patients usually dwelled in rural/suburban areas (82%), lived in poverty (75%), had a low education level (91%), and were heavy smokers (76%). Phimosis (57%), moderate/poor hygienic habits (90%), and history of sexually transmitted diseases (74%) were frequently found. Patients with >10 lifetime female partners had an odds ratio of 3.8 (95% CI 1.1, 12.6; P-trend = .03) for presenting HPV-positive tumors when compared to patients with <6 partners. However, this trend was not significant when the number of sexual partners was adjusted for age of first coitus and antecedents of sexually transmitted diseases. HPV-related tumors (found in 36% of the samples) were characterized by a warty and/or basaloid morphology and high histological grade in most cases. CONCLUSIONS: In our series, patients with penile cancer presented a distinctive epidemiologic and pathologic profile. These data might help explaining the geographical differences in incidence and aid in the design of strategies for cancer control in Paraguay.
Distribution and Characterization of Subtypes of Penile Intraepithelial Neoplasia and Their Association with Invasive Carcinomas: a Pathological Study of 139 Lesions in 121 Patients
We are presenting the morphological features of 121 cases of atypical penile intraepithelial lesions. The term penile intraepithelial neoplasia (PeIN) was used to encompass all of them, and lesions were classified into 2 major groups, differentiated and undifferentiated. The latter was further divided in warty, basaloid, and warty-basaloid subtypes. Ninety-five cases were associated with invasive squamous cell carcinomas. Differentiated lesions predominated (68%), followed by warty-basaloid (14%), basaloid (11%), and warty (7%) subtypes. Multifocality was found in 15% of the cases. Differentiated lesions were preferentially located in foreskin, whereas warty and/or basaloid subtypes were more prevalent in the glans. The former lesions were preferentially seen in association with keratinizing variants of squamous carcinoma, whereas the latter subtypes were found mostly in conjunction with invasive warty, basaloid, and warty-basaloid carcinomas. Lichen sclerosus was present in 51% of cases of differentiated lesions and absent in warty and/or basaloid subtypes. In summary, PeIN can be classified into 4 distinctive morphological subtypes. The proper pathological characterization of these lesions may provide important clues to the understanding of the pathogenesis and natural history of penile cancer.
