RESUMO
Nephrogenic adenoma (NA) is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with antecedent inflammation, instrumentation, or an operative history. Its histopathologic diversity can create diagnostic dilemmas and pathologists use morphologic evaluation along with available immunohistochemical (IHC) markers to navigate these challenges. IHC assays currently do not designate or specify NA's potential putative cell of origin. Leveraging single-cell RNA-sequencing technology, we nominated a principal (P) cell-collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for NA. IHC characterization revealed L1CAM to be positive in all 35 (100%) patient samples of NA; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma (UCA) in situ, prostatic adenocarcinoma, majority of high-grade UCA, and metastatic UCA. In the study, we also used single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for the proximal tubule, loop of Henle, and distal tubule (DT) (including P and intercalated cells), which can be used to perform nephronal mapping using RNA in situ hybridization and IHC technology. Employing this technique on NA we found enrichment of both the P-cell marker L1CAM and, the proximal tubule type-A and -B cell markers, PDZKI1P1 and PIGR, respectively. The cell-type markers for the intercalated cell of DTs (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in NA. Overall, our findings show that based on cell type-specific implications of L1CAM expression, the shared expression pattern of L1CAM between DT P cells and NA. L1CAM expression will be of potential value in assisting surgical pathologists toward a diagnosis of NA in challenging patient samples.
Assuntos
Adenoma , Biomarcadores Tumorais , Molécula L1 de Adesão de Célula Nervosa , Humanos , Molécula L1 de Adesão de Célula Nervosa/análise , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Molécula L1 de Adesão de Célula Nervosa/biossíntese , Adenoma/patologia , Adenoma/metabolismo , Masculino , Biomarcadores Tumorais/análise , Feminino , Idoso , Pessoa de Meia-Idade , Imuno-Histoquímica , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/genética , Néfrons/patologia , Néfrons/metabolismo , AdultoRESUMO
Anogenital herpes simplex virus (HSV) infection can rarely manifest as a pseudotumor, which some have termed "hypertrophic herpes." Almost all cases are in immunocompromised patients, typically with human immunodeficiency virus/acquired immune deficiency syndrome. This presentation often mimics malignancy clinically. We present a case of cervical HSV pseudotumor with associated lymphadenopathy in an immunocompetent woman, mimicking locally advanced cervical cancer. The lesion resolved with acyclovir therapy. We emphasize that (1) clinically suspected malignancy must be confirmed by pathologic examination; (2) infectious mimics must be considered when microscopic examination fails to confirm a clinically suspected anogenital malignancy, particularly in patients with compromised or unknown immune status; (3) morphologic hallmarks of infection may be focal; (4) co-infection with multiple sexually transmitted infections can occur, particularly in immunocompromised patients, and HSV or other infection does not per se exclude concurrent human papillomavirus-associated neoplasia; and (5) anogenital HSV pseudotumor should prompt clinical evaluation for human immunodeficiency virus or other immunosuppression.
RESUMO
Atypical placental site nodules (APSNs) are histologically intermediate between placental site nodules (PSNs) and epithelioid trophoblastic tumors (ETTs). Little data exists to characterize these lesions and the risk of transformation from PSN to ETT. Recent World Health Organization (WHO) criteria for distinction of APSN are vague and not objectively defined. We identified cases signed out as PSN (n=33) and APSN (n=11) and aimed to characterize, statistically compare, and assess the risk of transformation in PSNs using data including size, location, mitotic rate, Ki-67 proliferation index, trophoblastic cells per high-power field, presence of severe cytologic atypia, beta-human chorionic gonadotropin levels, time since last pregnancy, presence of calcification, necrosis, or apoptosis, and follow-up results. All cases were confirmed to be positive for p63, and a Ki-67/AE1/AE3 dual stain was used to evaluate the Ki-67 proliferation index in the trophoblastic cells. In our cohort, slight changes in the interpretation of WHO criteria for PSN and APSN led to marked differences in the proportion of PSNs flagged as "atypical." There was no statistically significant difference in the persistence of APSN versus non-APSN. None of the PSNs transformed to ETT. Current criteria for distinction between PSN and APSN are largely subjective. More objective, clearly defined, and clinically meaningful criteria are needed to distinguish between PSN and APSN, thus aiding in assessing the rare risk of transformation to ETT.
Assuntos
Doença Trofoblástica Gestacional , Tumor Trofoblástico de Localização Placentária , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Tumor Trofoblástico de Localização Placentária/diagnóstico , Tumor Trofoblástico de Localização Placentária/patologia , Placenta/patologia , Antígeno Ki-67 , Neoplasias Uterinas/patologia , Doença Trofoblástica Gestacional/patologiaRESUMO
Recent studies have provided molecular confirmation that a subset of yolk sac tumors is somatically derived. Somatically derived yolk sac tumors are typically diagnosed in older women and are often seen adjacent to epithelial proliferations (such as endometriosis or endometrioid carcinoma) with which they share mutations. Here, we present a case of a postmenopausal woman with a yolk sac tumor and endometriosis in the right ovary, endometriosis with glandular crowding and reactive changes in the left ovary, endometrial endometrioid carcinoma, and yolk sac tumor involving the serosa of the colon. Targeted next-generation sequencing of these five tumor components demonstrated identical mutations in PTEN (p.R130G), PIK3CA (p.G1049S), FGFR2 (p.S252W), and FBXW7 (p.R689Q), suggesting that all components arose from a common precursor. The endometrial endometrioid carcinoma harbored additional exclusive mutations involving PIK3CA (p.H1048R) and CTNNB1 (p.S37F).
Assuntos
Carcinoma Endometrioide , Tumor do Seio Endodérmico , Endometriose , Neoplasias Ovarianas , Neoplasias Peritoneais , Endometriose/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Tumor do Seio Endodérmico/genética , Tumor do Seio Endodérmico/patologia , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Humanos , Feminino , Pessoa de Meia-IdadeRESUMO
This report describes 3 cases of ovarian tumors with unusual glandular proliferations co-expressing estrogen receptor and CDX-2 by immunohistochemistry set in cystadenofibromatous background. Targeted next-generation sequencing was performed on the cyst lining epithelium and glandular proliferations for all cases; CTNNB1 mutations were detected in the glandular proliferations of all neoplasms. The cyst lining of case 1 demonstrated a different CTNNB1 mutation from the matched glandular proliferation. No mutations were detected in the cyst lining from case 2. The cyst lining and glandular proliferation for case 3 harbored identical ATM and PIK3CA mutations with an additional CTNNB1 mutation in the glandular proliferation. To our knowledge, this is the first reported series of endometrioid proliferations with co-expression of estrogen receptor and CDX-2 in cystadenofibromatous background.
Assuntos
Carcinoma Endometrioide , Cistos , Neoplasias Ovarianas , Feminino , Humanos , Receptores de Estrogênio/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Imuno-Histoquímica , Mutação , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologiaRESUMO
AIMS: Distinction between well-differentiated endometrial carcinoma (EMCA) with microglandular/mucinous features and benign endocervical microglandular hyperplasia (MGH) can be a diagnostic challenge, especially when tissue is limited. The immunostains used to distinguish endocervical and endometrial carcinoma are less useful when the differential diagnosis is MGH. Here, we investigate the utility of p63 and phosphatase and tensin homologue (PTEN) to aid accurate classification. METHODS AND RESULTS: Cases obtained from our pathology archives included 25 EMCA with mucinous/microglandular features, 26 MGH and nine atypical microglandular proliferations. Cases were assessed for glandular architecture, presence of mucinous and/or eosinophilic luminal secretions, subnuclear vacuoles, foamy histiocytes, inflammation, squamous metaplasia, cytological atypia and mitotic activity. The presence and pattern of immunohistochemical staining for p63 and PTEN was recorded. Microglandular proliferations with cytological atypia, mitotic activity, foamy histiocytes and complex glandular architecture were more commonly seen in EMCA, while small glands, bland nuclei and subnuclear vacuoles were enriched in MGH. All MGH cases displayed p63-positive subcolumnar reserve cells and retained PTEN expression. Four EMCA cases showed non-specific focal p63 staining either at the surface of the tumour or in areas of squamous differentiation. p63 and PTEN immunostains accurately predicted the final diagnosis for 3 atypical microglandular proliferation cases with follow-up. CONCLUSIONS: While there are morphological characteristics that differentiate EMCA and MGH, there is frequent overlap between these entities. Nonetheless, the pattern and extent of p63 and PTEN can aid accurate classification. Consistent p63-positive subcolumnar reserve cells were seen only in MGH.
Assuntos
Carcinoma Endometrioide , Carcinoma de Células Escamosas , Hiperplasia Endometrial , Neoplasias do Endométrio , Carcinoma Endometrioide/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Diagnóstico Diferencial , Hiperplasia Endometrial/diagnóstico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Hiperplasia/diagnóstico , PTEN Fosfo-Hidrolase , Coloração e RotulagemRESUMO
AIMS: As gender-affirming surgery is becoming more common, it is important for pathologists to recognize potential benign findings to avoid misinterpretation. Cervical transitional cell metaplasia and superficial clusters of small basophilic cells have been described in the context of gender-affirming testosterone therapy; these findings may be misdiagnosed as high-grade squamous intraepithelial lesions or endometrial cells on Pap smears. Prostatic metaplasia has been reported in the surface squamous epithelium of the vagina and the uterine cervix in individuals undergoing gender-affirming androgen therapy; this finding is often associated with NKX3.1-positive basal keratinocytes. The aim of this study was to assess the morphological and immunohistochemical features of the uterine cervix in gender-affirming hysterectomies in comparison with benign hysterectomies from cisgender women. METHODS AND RESULTS: We assessed the morphological and immunohistochemical features of the uterine cervix in 49 gender-affirming hysterectomies as compared with 57 hysterectomies from cisgender patients to establish the relative prevalences of surface prostatic metaplasia, NKX3.1-positive basal keratinocytes, transitional cell metaplasia, and small basophilic cells in the cervical squamous epithelium. The cervical tissue from the gender-affirming therapy cohort showed significantly higher prevalences of NKX3.1-positive basal keratinocytes (86% versus 1.8%), transitional cell metaplasia (80% versus 3.5%), superficial clusters of small basophilic cells (67% versus 7%), and surface prostatic metaplasia (43% versus 3.5%). CONCLUSION: NKX3.1-positive basal keratinocytes, transitional cell metaplasia, small basophilic cells and surface prostatic metaplasia are all more prevalent in the cervices of individuals receiving gender-affirming testosterone therapy; awareness of this fact allows pathologists to avoid the overdiagnosis of dysplasia or the recommendation of unnecessary follow-up procedures.
Assuntos
Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Carcinoma de Células Escamosas/patologia , Colo do Útero/patologia , Feminino , Humanos , Histerectomia , Metaplasia/patologia , Prevalência , Testosterona , Neoplasias do Colo do Útero/patologiaRESUMO
While most ovarian follicle cysts are <8 cm in greatest dimension, much larger follicle cysts (up to 18.5 cm) have been reported. To our knowledge, the FOXL2 mutation status of such cases has not been documented in the literature. Here, we report the features of a 14 cm ovarian cyst with no FOXL2 mutation detected by targeted next-generation sequencing. While adult granulosa cell tumor was the chief entity in our differential diagnosis, the absence of convincing nuclear grooves, lack of architectural variability, presence of a theca layer, and absence of FOXL2 mutation were consistent with a diagnosis of ovarian follicle cyst.
Assuntos
Tumor de Células da Granulosa , Cistos Ovarianos , Neoplasias Ovarianas , Adulto , Feminino , Proteína Forkhead Box L2/genética , Tumor de Células da Granulosa/diagnóstico , Tumor de Células da Granulosa/genética , Tumor de Células da Granulosa/patologia , Células da Granulosa/patologia , Humanos , Mutação , Cistos Ovarianos/diagnóstico , Cistos Ovarianos/patologia , Folículo Ovariano/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologiaRESUMO
Uterine PEComatosis is a rare phenomenon characterized by the presence of multiple perivascular epithelioid cell tumors (PEComas) and/or microscopic proliferations of perivascular epithelioid cells. Herein, we report a case of PEComatosis arising in a 49-yr-old woman with a known history of tuberous sclerosis. Targeted next-generation sequencing revealed a TSC1 stopgain mutation (p.Q732X) in all tested nodules, with single-copy TSC1 loss or copy-neutral TSC1 loss of heterozygosity. To our knowledge, this is the second report of TSC1 inactivation in uterine PEComa and the first report of confirmed TSC1 abnormalities in PEComatosis.
Assuntos
Neoplasias de Células Epitelioides Perivasculares , Esclerose Tuberosa , Células Epitelioides/patologia , Feminino , Humanos , Mutação , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/patologia , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genética , Esclerose Tuberosa/patologia , Útero/patologiaRESUMO
Accurate diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) is challenging, in part due to the sometimes subtle nature of its atypia. Many dVIN lesions demonstrate aberrant p53 staining; however, staining patterns overlap between dVIN and benign/reactive entities. We evaluate a p53/CK17 dual stain in an initial cohort of dVIN (n=30), benign vulvar skin (n=5), lichen sclerosus (LS, n=10), lichen simplex chronicus (LSC, n=10), and pseudoepitheliomatous hyperplasia (PEH, n=10). In the initial cohort, aberrant p53 staining was seen only in dVIN (50%, 15/30). Equivocal p53 staining patterns were seen in dVIN (37%, 11/30), LS (50%, 5/10), LSC (40%, 4/10), and PEH (40%, 4/10). All 30 dVIN cases were positive for CK17 (strong partial-thickness or full-thickness staining), but positive CK17 staining was also seen in LS (70%, 7/10), LSC (50%, 5/10), and PEH (100%, 10/10). In the initial cohort, the combination of aberrant p53 and positive CK17 was seen only for dVIN (50%, 15/30). Forty cases of LS with known follow-up (20 with progression to dVIN, 20 without) were stained to assess prognostic value. Three LS cases showed aberrant p53 staining with CK17 positivity; all progressed to dVIN. Equivocal p53 staining and CK17 positivity were seen in cases with and without progression. The p53/CK17 dual stain is more diagnostically useful than either stain alone. Negative/focal staining for CK17 argues against a diagnosis of dVIN, while aberrant p53 staining with CK17 positivity strongly supports the diagnosis.
Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Lesões Intraepiteliais Escamosas , Proteína Supressora de Tumor p53/metabolismo , Líquen Escleroso Vulvar , Neoplasias Vulvares , Biomarcadores Tumorais , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Corantes , Feminino , Humanos , Líquen Escleroso Vulvar/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/patologiaRESUMO
OBJECTIVE: This study aimed to determine if treating lichen sclerosus (LS) with high-potency topical corticosteroids (TCS) increases the risk of high-grade squamous intraepithelial lesion (HSIL) recurrence in patients with comorbid vulvar LS and HSIL. METHODS: This is a retrospective study of patients with comorbid vulvar LS and HSIL treated with TCS between 2015 and 2020. Patients with clinically diagnosed or biopsy-proven LS and biopsy-proven HSIL of the vulva were included. Clinical data included demographics, tobacco use, immune-modifying conditions, specimen pathology, treatment types, and HSIL recurrence. Bivariate analysis was performed to compare demographic and clinical characteristics between patients with and without HSIL recurrence. RESULTS: Twenty-six patients with comorbid LS and HSIL were identified. The median age was 66.0 years and median time in treatment for LS was 5.5 years. Thirteen (50%) had recurrence of HSIL and 13 (50%) did not have recurrence. Exposure to high-potency TCS was present in 20 (77%) patients, with 17 (65%) having use of more than 1-year duration and 9 (35%) having use at the time of HSIL diagnosis. When comparing the groups with and without HSIL recurrence, there was no significant difference in high-potency TCS exposure, duration of use, or use at time of HSIL diagnosis. CONCLUSIONS: High-potency TCS use for the treatment of LS did not seem to increase the risk of HSIL recurrence in patients with comorbid vulvar LS and HSIL. This suggests that high-potency TCS can be appropriately used for the treatment of LS even when HPV-associated disease is present.
Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Líquen Escleroso e Atrófico , Lesões Intraepiteliais Escamosas , Líquen Escleroso Vulvar , Neoplasias Vulvares , Corticosteroides , Idoso , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Líquen Escleroso e Atrófico/patologia , Estudos Retrospectivos , Lesões Intraepiteliais Escamosas/epidemiologia , Líquen Escleroso Vulvar/complicações , Líquen Escleroso Vulvar/epidemiologia , Líquen Escleroso Vulvar/patologia , Neoplasias Vulvares/complicações , Neoplasias Vulvares/epidemiologia , Neoplasias Vulvares/patologiaRESUMO
Microphthalmia-associated transcription factor (MiT) family aberration-associated renal cell carcinoma (MiTF-RCC) is a subtype of renal cell carcinoma harboring recurrent chromosomal rearrangements involving TFE3 or TFEB genes. MiTF-RCC is morphologically diverse, can histologically resemble common RCC subtypes like clear cell RCC and papillary RCC, and often poses a diagnostic challenge in genitourinary clinical and pathology practice. To characterize the MiTF-RCC at the molecular level and identify biomarker signatures associated with MiTF-RCC, we analyzed RNAseq data from MiTF-RCC, other RCC subtypes and benign kidney. Upon identifying TRIM63 as a cancer-specific biomarker in MiTF-RCC, we evaluated its expression independently by RNA in situ hybridization (RNA-ISH) in whole tissue sections from 177 RCC cases. We specifically included 31 cytogenetically confirmed MiTF-RCC cases and 70 RCC cases suspicious for MiTF-RCC in terms of clinical and morphological features, to evaluate and compare TRIM63 RNA-ISH results with the results from TFE3/TFEB fluorescence in situ hybridization (FISH), which is the current clinical standard. We confirmed that TRIM63 mRNA was highly expressed in all classes of MiTF-RCC compared to other renal tumor categories, where it was mostly absent to low. While the TRIM63 RNA-ISH and TFE3/TFEB FISH results were largely concordant, importantly, TRIM63 RNA-ISH was strongly positive in TFE3 FISH false-negative cases with RBM10-TFE3 inversion. In conclusion, TRIM63 can serve as a diagnostic marker to distinguish MiTF-RCC from other renal tumor subtypes with overlapping morphology. We suggest a combination of TFE3/TFEB FISH and TRIM63 RNA-ISH assays to improve the accuracy and efficiency of MiTF-RCC diagnosis. Accurate diagnosis of MiTF-RCC and other RCC subtypes would enable effective targeted therapy and avoid poor therapeutic response due to tumor misclassification.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Proteínas Musculares/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Fator de Transcrição Associado à Microftalmia/genética , Proteínas Musculares/análise , Fusão Oncogênica , Sensibilidade e Especificidade , Translocação Genética , Proteínas com Motivo Tripartido/análise , Ubiquitina-Proteína Ligases/análiseRESUMO
AIMS: Atypical polypoid adenomyoma (APAM) is an uncommon uterine lesion composed of complex endometrioid glands with frequent squamous morular metaplasia and fibromuscular stroma. On endometrial curettage, biopsy or polypectomy specimens, the admixture of endometrioid glands and smooth muscle raises the differential diagnosis of myoinvasive endometrioid carcinoma. Reproductive-age APAM patients may opt for fertility preservation, whereas myoinvasive carcinoma is treated surgically. One previous study reported an incidental finding that the stroma of APAM, in contrast to that of other polypoid lesions, was SATB2-positive. APAM has also been reported to show increased stromal p16 staining. We aimed to assess whether SATB2 and p16 are useful stains for the distinction of APAM from myoinvasive carcinoma and benign adenomyomatous polyps. METHODS AND RESULTS: Cases of 'atypical polypoid adenomyoma' (n = 32), 'adenomyomatous polyp' (n = 39) and 'myoinvasive endometrioid carcinoma' (n = 30) were identified. Morphological features were assessed, along with the intensity and extent of SATB2 and p16 staining in the stromal component of each lesion. SATB2 expression was seen in the stromal components of 30 of 32 (94%) APAMs, versus none of 39 (0%) benign adenomyomatous polyps and five of 30 (17%) myoinvasive endometrioid carcinomas. Stromal p16 expression was seen in 31 of 31 (100%) APAMs, versus 20 of 39 (51%) benign adenomyomatous polyps and 12 of 30 (40%) myoinvasive endometrioid carcinomas. CONCLUSIONS: Patchy to diffuse SATB2 and block-type p16 staining of fibromuscular stroma separating atypical endometrioid glands is more consistent with APAM than with myoinvasive endometrioid carcinoma. These stains are potentially useful adjuncts to careful morphological evaluation of endometrial biopsies/curettings.
Assuntos
Adenomioma/diagnóstico , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Proteínas de Ligação à Região de Interação com a Matriz/biossíntese , Fatores de Transcrição/biossíntese , Neoplasias Uterinas/diagnóstico , Pólipos Adenomatosos/diagnóstico , Adenomioma/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Endometrioide/diagnóstico , Diagnóstico Diferencial , Neoplasias do Endométrio/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Uterinas/patologia , Adulto JovemRESUMO
Squamous cell carcinoma of the vulva can arise through 2 pathways: human papillomavirus (HPV)-dependent high-grade squamous intraepithelial lesions (previously termed usual vulvar intraepithelial neoplasia) or HPV-independent (differentiated vulvar intraepithelial neoplasia, dVIN). Distinguishing between the 2 types can be clinically and histologically difficult. A subset of high-grade squamous intraepithelial lesions with superimposed chronic inflammation mimicking dVIN has recently been reported; p53 shows characteristic mid-epithelial staining (with basal sparing) in such cases. The pathology databases of 2 academic institutions were searched for vulva specimens with corresponding p53 and p16 immunohistochemical stains, yielding 38 specimens (from 27 patients). In situ hybridization and multiplex polymerase chain reaction-MassArray for high-risk HPV were performed on at least 1 block from each patient. All cases resembled dVIN or lichen sclerosus morphologically, but with a higher degree of atypia. All but 1 case demonstrated mid-epithelial p53 staining with basal sparing by immunohistochemistry. All cases showed block positivity for p16 and at least patchy positivity by HPV in situ hybridization. Of the 23 cases with valid HPV DNA polymerase chain reaction results, 15 were positive and 8 were negative. Of the positive cases, HPV16 was identified in 10 cases, with other high-risk types in the remaining 5. To our knowledge, this is the largest cohort of high-grade squamous intraepithelial lesions mimicking dVIN reported to date. Prior studies reported positivity for HPV16 in all cases tested, however, we found HPV16 in only 67% of HPV positive cases. This case series highlights the importance of immunohistochemistry, and occasionally HPV in situ hybridization, for accurate diagnosis, and expands the spectrum of associated HPV types.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Lesões Intraepiteliais Escamosas/patologia , Líquen Escleroso Vulvar/patologia , Neoplasias Vulvares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/virologia , Estudos de Coortes , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Papillomavirus Humano 16/genética , Humanos , Hibridização In Situ , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas/diagnóstico , Lesões Intraepiteliais Escamosas/virologia , Proteína Supressora de Tumor p53/metabolismo , Vulva/patologia , Vulva/virologia , Líquen Escleroso Vulvar/diagnóstico , Líquen Escleroso Vulvar/virologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/virologiaRESUMO
Follicle center lymphomas, including primary cutaneous follicle center lymphoma (PCFCL), may rarely show plasmacytic differentiation. Such cases can pose a diagnostic challenge and can be mistaken for other lymphomas that more commonly include plasma cells. Here, we report four cases of PCFCL and one case of systemic follicular lymphoma involving the skin with associated monotypic plasma cells, including the clinical, morphologic and immunophenotypic features.
Assuntos
Cadeias kappa de Imunoglobulina/metabolismo , Linfoma de Células B/diagnóstico , Linfoma Folicular/diagnóstico , Plasmócitos/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Biópsia , Diferenciação Celular , Feminino , Humanos , Cadeias lambda de Imunoglobulina/metabolismo , Imunofenotipagem/métodos , Linfoma de Células B/patologia , Linfoma Folicular/cirurgia , Linfoma Folicular/ultraestrutura , Masculino , Pessoa de Meia-Idade , Plasmócitos/metabolismo , Resultado do TratamentoRESUMO
Ovarian germ cell tumors, including yolk sac tumors, are most commonly diagnosed in children and young women. Most so-called yolk sac tumors reported in women >35 years old have been associated with an epithelial proliferation (endometriosis or carcinoma). Here, we describe eight cases clinically diagnosed as uterine or ovarian germ cell tumors in women >35 years old. In addition to routine morphologic examination and immunohistochemical evaluation, we present data from targeted next-generation sequencing (NGS) and isochromosome (12p) fluorescence in situ hybridization (FISH). We identified two groups of tumors with mixed germ cell and epithelial features: (1) tumors with background endometriosis and endometrioid carcinoma-like mutations (PTEN, PIK3CA, FGFR2, and CTNNB1), and (2) high-grade morphology, presumptive presence of isochromosome (12p) by FISH, and TP53 or PIK3CA mutations. These findings support the notion that the "germ cell tumor" component of these tumors is often somatically derived. Two tumors in our cohort were from premenopausal women; one showed no detectable mutations by NGS (suggestive of germ cell derivation), whereas the other showed PIK3CA, PTEN, and CTNNB1 mutations (suggestive of somatic derivation). Accurate classification of these tumors is likely important for selection of appropriate chemotherapy.
Assuntos
Carcinoma Endometrioide/patologia , Tumor do Seio Endodérmico/patologia , Neoplasias Complexas Mistas/patologia , Neoplasias Ovarianas/patologia , Neoplasias Uterinas/patologia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Mesonephric adenocarcinoma is a rare tumor, accounting for <1% of cervical cancers. Well-differentiated mesonephric adenocarcinoma can be difficult to distinguish from diffuse mesonephric hyperplasia. Herein, we report a case of well-differentiated mesonephric adenocarcinoma with an FGFR2 mutation not previously reported in the literature. Nonselective tyrosine kinase inhibitors or FGFR2 inhibitors may represent options for targeted therapy.
Assuntos
Adenocarcinoma/diagnóstico , Mesonefroma/diagnóstico , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Colo do Útero/patologia , Diagnóstico Diferencial , Feminino , Humanos , Mesonefroma/genética , Mesonefroma/patologia , Mutação , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVES: Despite poor reproducibility for measuring vulvar cancer depth, 1-mm or greater invasion triggers lymphadenectomy for small tumors. Previous literature suggests that measuring depth from the nearest dysplastic rete peg (alternative method) rather than highest dermal papilla (conventional method) may be acceptable. METHODS: Pathologic staging and follow-up information were recorded for 100 pT1 vulvar squamous cell carcinoma (SCC) resected from 1990 to 2019. Conventional depth, alternative depth, gross/clinical size, and size of the invasive component were measured for each tumor. In this retrospective study, we evaluated which clinicopathologic factors were most predictive of lymph node involvement and recurrence. RESULTS: Depending on the measurements used (conventional vs alternative depth, clinical lesion size vs cumulative extent of invasive component), between 1 and 18 cases were downstaged to pT1a. All such cases were pN0, without lymphovascular or perineural invasion. Infiltrative cords (hazard ratio [HR] = 5.15; 95% CI = 1.63-16.2; p = .005) and perineural invasion (HR = 3.16; 1.18-8.45; p = .022) were most strongly associated with groin recurrence. Of staging criteria evaluated, only cumulative extent of the invasive component 2 cm or greater was significantly associated with groin recurrence (HR = 2.87; 1.01-8.17; p = .048). The Kaplan-Meier curves for local recurrence-free survival by stage did not show significant separation regardless of method. CONCLUSIONS: Patients downstaged using alternative measurement techniques lacked nodal disease/recurrence; one-third of those with nodal sampling experienced postoperative morbidity. Our data suggest that the use of alternative depth and cumulative extent of invasion could safely allow some conventional stage IB vulvar SCC patients to avoid groin surgery, thereby reducing treatment-related morbidity.
Assuntos
Carcinoma de Células Escamosas/patologia , Estadiamento de Neoplasias/métodos , Neoplasias Vulvares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Virilha/patologia , Humanos , Michigan , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Medição de Risco , Adulto JovemRESUMO
PURPOSE: Metaplastic breast carcinomas are an aggressive subtype of triple-negative breast cancer (TNBC) in which part or all of the adenocarcinoma transforms into a non-glandular component (e.g., spindled, squamous, or heterologous). We discovered that mammary-specific Ccn6/Wisp3 knockout mice develop mammary carcinomas with spindle and squamous differentiation that share upregulation of the oncofetal proteins IGF2BP2 (IMP2) and HMGA2 with human metaplastic carcinomas. Here, we investigated the functional relationship between CCN6, IGF2BP2, and HMGA2 proteins in vitro and in vivo, and their expression in human tissue samples. METHODS: MMTV-cre;Ccn6fl/fl tumors and spindle TNBC cell lines were treated with recombinant CCN6 protein or vehicle. IGF2BP2 was downregulated using shRNAs in HME cells with stable CCN6 shRNA knockdown, and subjected to invasion and adhesion assays. Thirty-one human metaplastic carcinomas were arrayed in a tissue microarray (TMA) and immunostained for CCN6, IGF2BP2, and HMGA2. RESULTS: CCN6 regulates IGF2BP2 and HMGA2 protein expression in MMTV-cre;Ccn6fl/fl tumors, in MDA-MB-231 and - 468, and in HME cells. CCN6 recombinant protein reduced IGF2BP2 and HMGA2 protein expression, and decreased growth of MMTV-cre;Ccn6fl/fl tumors in vivo. IGF2BP2 shRNA knockdown was sufficient to reverse the invasive abilities conferred by CCN6 knockdown in HME cells. Analyses of the TCGA Breast Cancer Cohort (n = 1238) showed that IGF2BP2 and HMGA2 are significantly upregulated in metaplastic carcinoma compared to other breast cancer subtypes. In clinical samples, low CCN6 is frequent in tumors with high IGF2BP2/HMGA2 with spindle and squamous differentiation. CONCLUSIONS: These data shed light into the pathogenesis of metaplastic carcinoma and demonstrate a novel CCN6/IGF2BP2/HMGA2 oncogenic pathway with biomarker and therapeutic implications.
Assuntos
Proteínas de Sinalização Intercelular CCN/fisiologia , Proteína HMGA2/fisiologia , Proteínas de Ligação a RNA/fisiologia , Transdução de Sinais/fisiologia , Neoplasias de Mama Triplo Negativas/patologia , Animais , Adesão Celular , Linhagem Celular Tumoral , Feminino , Proteína HMGA2/análise , Humanos , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Ligação a RNA/análise , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
Renal cell carcinomas with MITF aberrations demonstrate a wide morphologic spectrum, highlighting the need to consider these entities within the differential diagnosis of renal tumors encountered in clinical practice. Herein, we describe our experience with application of clinical fluorescence in situ hybridization (FISH) assays for detection of TFE3 and TFEB gene aberrations from 85 consecutive renal cell carcinoma cases submitted to our genitourinary FISH service. Results from 170 FISH assays performed on these tumors were correlated with available clinicopathologic findings. Ninety-eight percent of renal tumors submitted for FISH evaluation were from adult patients. Thirty-one (37%) tumors were confirmed to demonstrate MITF aberrations (21 TFE3 translocation, 4 TFEB translocation, and 6 TFEB amplification cases). Overall, renal cell carcinomas with MITF aberrations demonstrated morphologic features overlapping with clear cell, papillary, or clear cell papillary renal cell carcinomas. Renal cell carcinomas with MITF aberrations were significantly more likely to demonstrate dual (eosinophilic and clear) cytoplasmic tones (P=0.030), biphasic TFEB translocation renal cell carcinoma-like morphology (P=0.002), psammomatous calcifications (P=0.002), and nuclear pseudoinclusions (P=0.001) than renal cell carcinomas without MITF aberrations. Notably, 7/9 (78%) renal cell carcinomas exhibiting subnuclear clearing and linear nuclear array (6 of which showed high World Health Organization/International Society of Urological Pathology nucleolar grade) demonstrated TFE3 translocation, an association that was statistically significant when compared with renal cell carcinomas without MITF aberrations (P=0.009). In this cohort comprising consecutive cases, TFEB-amplified renal cell carcinomas were more commonly identified than renal cell carcinomas with TFEB translocations, and four (67%) of these previously unreported TFEB-amplified renal cell carcinomas demonstrated oncocytic and papillary features with a high World Health Organization/International Society of Urological Pathology nucleolar grade. In summary, TFE3 and TFEB FISH evaluation aids in identification and accurate classification of renal cell carcinomas with MITF aberrations, including TFEB-amplified renal cell carcinoma, which may demonstrate aggressive behavior.