Abha Goyal

Differential patterns of PAX8, p16, and ER immunostains in mesonephric lesions and adenocarcinomas of the cervix.

Mesonephric remnants, usually located deep in the lateral cervical wall, may become hyperplastic resulting in a florid proliferation. These can be misinterpreted as malignant and confused with endocervical adenocarcinomas. Recent data have shown that PAX2 is diffusely expressed in mesonephric remnants and hyperplasias. PAX8 is a related transcription protein that is expressed in tissues of müllerian and wolffian origin. In this study, we have investigated the utility of an immunohistochemical panel comprising of PAX8, estrogen receptor (ER), and p16 in the differential diagnosis between mesonephric proliferations and cervical adenocarcinomas. A database search was conducted for cases of mesonephric remnants/hyperplasia/carcinoma of cervix and invasive cervical adenocarcinomas. Immunohistochemical stains for PAX8, ER, and p16 were performed using the avidin-biotin peroxidase technique on the most representative tissue. The search yielded 28 cases of mesonephric proliferations of cervix (15 mesonephric remnants, 12 mesonephric hyperplasias, and 1 mesonephric adenocarcinoma) and 16 cases of cervical adenocarcinomas (15 usual type and 1 adenoma malignum). Immunohistochemically, all the mesonephric proliferations, regardless of being benign or malignant, displayed a consistent staining pattern—diffusely and strongly positive for PAX8, negative for ER, and patchy cytoplasmic staining for p16. The usual type cervical adenocarcinomas exhibited a variable staining pattern with PAX8 and ER but all were strongly and diffusely positive for p16. The case of adenoma malignum was PAX8 positive, ER negative, and showed weak and patchy staining with p16. Our study suggests that a panel of immunohistochemical stains composed of PAX8, p16, and ER is useful in the distinction between mesonephric proliferations and cervical adenocarcinomas.

Value of PAX-8 and SF-1 Immunohistochemistry in the Distinction Between Female Adnexal Tumor of Probable Wolffian Origin and its Mimics.

Female adnexal tumors of probable wolffian origin (FATWOs) are rare. They can closely mimic endometrioid adenocarcinomas with a prominent spindle cell component and Sertoli cell tumors (SCTs). To further define their immunohistochemical profile and origin, we investigated the expression of PAX-8, PAX-2, and GATA binding protein 3 (GATA-3) (wolffian markers) and of steroidogenic factor-1 (SF-1) (sex-cord stromal marker) in FATWOs. We also studied the expression of PAX-8 and PAX-2 in endometrioid adenocarcinomas; of SF-1 in Sertoli-Leydig cell and SCTs; and of PAX-8, PAX-2, GATA-3, and SF-1 in rete ovarii—a proposed site of origin for FATWOs. A database search yielded 8 FATWOs, 18 ovarian/tubal/paraovarian endometrioid adenocarcinomas, and 8 ovarian Sertoli-Leydig cell and SCTs. Eleven cases with rete ovarii sections were included. Of the FATWOs studied, all were negative for PAX-8, PAX-2, GATA-3, and SF-1. Of the endometrioid adenocarcinomas studied, PAX-8 was positive in all and PAX-2 was positive in 57%. Of the Sertoli-Leydig cell and SCTs, all were positive for SF-1 except one. The rete ovarii were positive for PAX-8, weakly positive for SF-1, and negative for PAX-2 and GATA-3. Our study suggests that PAX-8 and SF-1 can be helpful in the distinction between FATWOs and endometrioid adenocarcinomas and SCTs, respectively. Our results do not support a Mullerian or sex-cord stromal or rete ovarii origin for FATWOs. It is curious, however, that FATWOs do not express wolffian markers—it is possibly related to their origin from a distinctive portion of the wolffian duct.

Cytologic categorization of pancreatic neoplastic mucinous cysts with an assessment of the risk of malignancy: A retrospective study based on the Papanicolaou Society of Cytopathology guidelines.

Cytology plays a pivotal role in the preoperative diagnosis of pancreatic cysts. Here the Papanicolaou Society of Cytopathology (Pap Society) guidelines were used to reclassify and assess the malignancy risk of cytology diagnoses of histologically proven pancreatic neoplastic mucinous cysts.

Adult rhabdomyoma: A challenging diagnosis on cytology

To the Editor, Rhabdomyoma is a rare benign neoplasm of striated muscle, which can be divided into cardiac and extracardiac forms. Of the extracardiac ones, there are three subtypes: adult, fetal, and genital. The adult type has a predilection for the head and neck of elderly males. These tumors originate from the branchial musculature of the third and fourth branchial arches.[1] Clonal structural chromosomal abnormalities including reciprocal translocation between chromosomes 15 and 17 (in the majority) and abnormalities of the long arm of chromosome 10 have been demonstrated in these tumors, indicating that they are neoplasms rather than hamartomas.[2] Given that these tumors are often found in the head and neck area, they lend themselves to fine needle aspiration (FNA). We would like to present a case of a 63-year-old female who presented to our otolaryngologist with a left-sided hypopharyngeal mass of 5.8 cm. The patient had a diagnosis of granular cell tumor on an FNA from an outside institution. As per the hospital protocol, her outside pathology slides were requested for review. We received FNA slides consisting of Papanicolaou stained smears, H andE stained cytospin preparations, and an Hand stained cell block slide with limited material. The slides revealed a cellular aspirate composed of large cells with well-defined, abundant, dense eosinophilic cytoplasm and mostly peripherally located nuclei [Figure 1]. The nuclear chromatin was vesicular and the nucleoli were prominent [Figure 2]. There were interspersed blood vessels. No definite cross-striations or crystals were identified. No mitotic activity or necrosis was seen. Immunohistochemical stains could not be performed due to paucity of material. Given the cytomorphology and location of this lesion, the differential diagnosis of adult rhabdomyoma versus granular cell tumor was raised. The tumor was resected and immunohistochemical stains performed on histologic sections revealed the lesion to be diffusely positive for muscle-specific actin, desmin, and myoglobin. The tumor was negative for S100, which supported the diagnosis of adult rhabdomyoma. Figure 1 Adult rhabdomyoma. The lesional tissue had a striking resemblance to skeletal muscle on low-power magnification (Papanicolaou stain, 100×) Figure 2 Adult rhabdomyoma. The cells exhibited abundant eosinophilic dense cytoplasm and peripherally located nuclei with vesicular chromatin and prominent nucleoli (H and E stain, cytospin preparation, 400×) The cytologic diagnosis of adult rhabdomyoma can be challenging, given the rarity of the tumor and the frequently encountered limited material. It is important to note that many characteristic features of this entity that are readily identified on histology are either missing or scarce on cytology. On histology, the tumor cells are composed of polygonal cells with eosinophilic granular cytoplasm that are intermixed with vacuolated cells. The vacuolation arises due to loss of intracellular glycogen during processing.[3] Further, some of these vacuolated cells appear as spider cells with a central mass of cytoplasm connected via thin strands to a condensed periphery. Striations can be seen in most cases [Figures ​[Figures33 and ​and4].4]. Intracytoplasmic “jackstraw”-like crystalline structures may also be found. In contrast, the cytologic picture lacks the effects of processing. One encounters individually dispersed or large cohesive clusters of round to polygonal cells with abundant eosinophilic granular cytoplasm, peripherally located (at times centrally located) uniform round nuclei with visible nucleoli, and traversing vessels.[3–14] Vacuolated cells have not been described on FNA smears although they have been easily appreciated on formalin-fixed cell block material.[8,9,14] Cross-striations are mostly not identified and, even if present, they are difficult to discern.[3–14] Cytoplasmic crystalline inclusions have only been identified occasionally.[3,10] Figure 3 Adult rhabdomyoma. “Spider cells” as seen on the histologic section of the surgical specimen (H and E stain, 400×) Figure 4 Adult rhabdomyoma. Striations easily identified on the histologic section of the surgical specimen (H and E stain, 400×) As is evident from above, lesions harboring cells with abundant granular cytoplasm that are prevalent in the head and neck region should be considered in the differential diagnosis of adult rhabdomyoma. A feature that was very obvious in our case is the remarkable similarity of the neoplastic cells to skeletal muscle on low-power magnification. The cells are large and polygonal with distinct cell borders. However, striations would be easy to find and wellformed in non-neoplastic skeletal muscle. Also, clinical and radiologic information regarding the presence of a well-defined mass would aid in the interpretation. Another entity that can simulate adult rhabdomyoma on cytology is granular cell tumor. These tumors occur in similar locations and have similar polygonal cells with abundant eosinophilic granular cytoplasm in syncytial cell clusters. But the cytoplasm of a granular cell tumor tends to be paler, less sharply defined, more soft and granular, as compared to that of adult rhabdomyoma [Figure 5].[15] A paraganglioma can also be considered in the differential diagnosis with its large polygonal cells, abundant granular cytoplasm, and rich vasculature. But the nuclear chromatin is finely stippled and the nucleoli are indistinct which help in its recognition. Neoplasms including hibernoma (with small cytoplasmic vacuoles), rhabdomyosarcoma (with prominent nuclear atypia), and oncocytoma of salivary gland (smaller cells with centrally located nuclei) can be easily distinguished from adult rhabdomyoma. Recently, a lymphoplasmacytic lymphoma with abundant immunoglobulin inclusions that mimicked adult rhabdomyoma on light microscopy has been described.[16] Figure 5 Granular cell tumor. In contrast to adult rhabdomyoma, the cytoplasm is less well defined, soft, and granular (Papanicolaou stain, ThinPrep, 400×) Additional material, if available, can be very useful in reaching a definitive diagnosis on FNA alone. The cell block morphology alone may give away the diagnosis with an admixture of granular cells and vacuolated cells and possible presence of striations and crystalline inclusions. Immunohistochemistry can serve as an important adjunct to the diagnosis. Adult rhabdomyomas are positive for desmin, myoglobin, and muscle-specific actin, and negative for S100 and CD68. Granular cell tumors tend to be diffusely positive for S100 and CD68. It is important to note that adult rhabdomyomas may show focal positivity to S100, so more than one stain should be performed when the differential diagnosis of adult rhabdomyoma and granular cell tumor is under consideration.[1] Paragangliomas exhibit S-100 positivity in the sustentacular cells and are also positive for markers of neuroendocrine differentiation such as chromogranin and synaptophysin. In most cases, adult rhabdomyomas can be treated by local excision. However, recurrences have been described in as many as 42% of cases, usually due to incomplete excision.[17] FNA can be an important tool in making a pre-operative diagnosis of adult rhabdomyoma, thereby reassuring the patient that the tumor is benign and enabling the correct management.

Application of p16 immunohistochemistry and RNA in situ hybridization in the classification of adenoid basal tumors of the cervix

Our understanding of adenoid basal tumors of the cervix has evolved over time. Most of the proliferations referred to as adenoid basal carcinoma have a clinically benign course—leading some to suggest the term “adenoid basal epithelioma.” However, rarely, these may be associated with invasive carcinomas. These tumors have been etiologically linked with high-risk human papillomavirus (HR-HPV) infection. Here, we investigate the use of p16 immunohistochemistry and HR-HPV RNA in situ hybridization (ISH) in the classification of adenoid basal tumors of the cervix. Seventeen cases of adenoid basal tumors of the cervix were included. The patients’ age ranged from 19 to 79 yr (average, 59 yr). p16 immunostain was performed on all cases and RNA ISH was performed in 4 cases with available formalin-fixed paraffin-embedded tissue. There were 11 low-grade tumors, 5 frankly invasive carcinomas, and 1 with histologic features that were intermediate between the former 2 categories. p16 immunostain was negative or showed patchy cytoplasmic staining in the low-grade tumors and was strongly and diffusely positive in the invasive carcinomas. HR-HPV RNA ISH was negative in the 3 low-grade tumors and was positive in 1 case of invasive carcinoma including the adenoid basal component. Distinct p16 immunostaining and HR-HPV RNA ISH patterns exist between low-grade adenoid basal tumors and invasive adenoid basal carcinomas. Our study indicates that p16 immunostaining and HR-HPV RNA ISH can be employed as useful ancillary tools in differentiating between noninvasive and invasive adenoid basal tumors along with careful histopathologic evaluation.