PAX8 plays a role in development of the thyroid, kidney, and the Wolffian and Mullerian tract. In surgical pathology, PAX8 immunohistochemistry is used to determine tumors of renal and ovarian origin, but data on its expression in other tumors are conflicting. To evaluate PAX8 expression in normal and tumor tissues, a tissue microarray containing 17,386 samples from 149 different tumor types and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. PAX8 results were compared with previously collected data on cadherin 16 (CDH16). PAX8 positivity was found in 40 different tumor types. The highest rate of PAX8 positivity was found in thyroidal neoplasms of follicular origin (98.6-100%), gynecological carcinomas (up to 100%), renal tumors (82.6-97.8%), and urothelial neoplasms (2.3-23.7%). Important tumors with near complete absence of PAX8 staining (< 1%) included all subtypes of breast cancers, hepatocellular carcinomas, gastric, prostatic, pancreatic, and pulmonary adenocarcinomas, neuroendocrine neoplasms, small cell carcinomas of various sites, and lymphomas. High PAX8 expression was associated with low tumor grade in 365 non-invasive papillary urothelial carcinomas (p < 0.0001) but unrelated to patient outcome and/or tumor phenotype in clear cell renal cell carcinoma, high-grade serous ovarian cancer, and endometrioid endometrial carcinoma. For determining a renal tumor origin, sensitivity was 88.1% and specificity 87.2% for PAX8, while sensitivity was 85.3% and specificity 95.7% for CDH16. The combination of PAX8 and CDH16 increased specificity to 96.8%. In conclusion, PAX8 immunohistochemistry is a suitable diagnostic tool. The combination of PAX8 and CDH16 positivity has high specificity for renal cell carcinoma.

Renal cell carcinoma (RCC) is common cancer derived from the renal epithelium. One of the rarest cases of RCC is sarcomatoid RCC (sRCC). The occurrence of sRCC in animals is not clearly demonstrated.
This study aimed to observe the clinicopathological characteristics of sRCC in animals from East Java, Indonesia, from 2017 to 2022.
This study used patients who were histopathologically diagnosed with sRCC in our laboratory from 2017 to 2022. The data on the clinical characteristics of animals, hematology, serology, histopathology, and immunohistochemistry (IHC) were retrieved and tabulated. The data were qualitatively and quantitatively analyzed using a simple descriptive method and Statistical Package for the Social Sciences version 26, respectively.
Fourteen cases of sRCC in animals have been identified in this study. It was found in rodents, dogs, and cats. sRCC predominantly occurred in rodents (57.14%) without specific clinical signs. The common histopathological findings of sRCC were epithelial renal cells transition into elongated atypical spindle cells. In addition, other histopathological patterns of a renal epithelial cell such as clear cell, tubule-cystic, and papillary also have been found. IHC by using antibodies demonstrates that PAX8 is expressed on sRCC tissue samples 92.85% (13/14 samples). Hence, PAX8 could be used as a supporting method for establishing the diagnosis of sRCC in animals. Hematology and serological tests did not correlate to the type of sRCC either pure sRCC or dedifferentiated sRCC. sRCC results in hypercreatinemia in rodents and dogs.
This study shows that the incidence of sRCC in animals is rare. Animals with sRCC did not show any specific clinical signs. The histopathological finding is quite difficult to be differentiated from the other RCC. PAX8 expression on renal tissue samples is useful in supporting the diagnosis of sRCC in animals.

Diagnosis of cystic papillary thyroid carcinoma (PTC) lymph node metastasis at head neck region can be a challenge in the absence of known PTC history. The congenital cystic lesions of head neck, especially thyroglossal duct cyst (TGDC) and branchial cleft cyst (BCC), are major differential diagnoses in this clinicopathological scenario. The location of cyst and morphology of lining epithelium are critical clues for reaching correct diagnosis. However it is not uncommon that the flattened bland epithelial lining can be seen in both cystic metastases and congenital cystic lesions. Given that Pax8 and TTF-1 are common markers in thyroid follicular epithelium; we applied immunohistochemical stains of those two markers on aforementioned cystic lesions. Here we reported a case of cystic PTC metastasis to lymph node without prior malignancy history and cases of TGDC and BCC. Both Pax8 and TTF-1 stainings highlighted the cyst lining in PTC metastatic lymph node, while they were negative in the lining of TGDC and BCC. Collectively, Pax8 and TTF-1 immunohistochemical studies are very helpful tools for making correct diagnosis of head neck cystic lesions in the challenging clinical cases.

OBJECTIVE: The aim of this study is to determine if the diagnosis of nephrogenic adenoma (NA) can be made on cytologic criteria alone and if pair box gene transcription factor 8 (PAX8) is useful in the diagnosis of NA in daily cytology practice.
METHODS: Cytologic features of NA previously described in a literature were used to identify NA cells in urinary specimens. Subsequently, all cytology and corresponding biopsy specimens were stained with the PAX8 immunohistochemistry stain. The stains were examined; the results were tabulated.
RESULTS: A total of 44 specimens were reviewed (35 with corresponding biopsy specimens diagnosed as NA and nine negative for NA diagnosis on corresponding biopsy specimens). Of them, 14 demonstrated features previously described as NA. None of atypical cells that were morphologically suspicious for NA showed positive staining, whereas all of the corresponding biopsy sections demonstrated nuclear PAX8 positivity. Only rare lymphocytes present in cytology specimens showed nuclear staining with PAX8.
CONCLUSIONS: Assuming that the results of the PAX8 stain performed are accurate at least in most cases, as suggested by the presence of internal positive controls, our study shows that the previously described cytologic features of NA cannot be used as diagnostic criteria, since they are not characteristic for this entity.

Brenner tumors are composed of urothelial/transitional-type epithelium and, hence, are morphologically similar to Walthard nests and tubal/mesothelial transitional metaplasia. In this study, we analyzed immunohistochemical markers on Brenner tumors to explore Müllerian as well as Wolffian and germ cell derivation. We also attempted to explore their possible association with tubal/paratubal Walthard nests/transitional metaplasia, using the same immunostains. Thirty-two consecutive cases of Brenner tumors were identified. Thirteen (43%) of the patients had Walthard nests in the tubal/periovarian soft tissue. All Brenner tumors were diffusely positive for GATA3 (strongly positive in 30/32 and weakly positive in the remaining 2) and negative for PAX8, PAX2, and SALL4. Similarly, all Walthard nests were positive for GATA3, whereas only 3 (23%) of 13 showed occasional PAX8 expression; all were negative for PAX2 and SALL4. In our study, more than 40% of Brenner tumors had associated Walthard nests. The similar morphology and immunoprofile of Brenner tumors and Walthard nests suggest a probable link between Brenner tumors and Walthard nests. Two additional cases presented highlight small transitional lesions involving the ovary: a possible precursor lesion or the initial steps of Brenner tumor formation. Brenner tumors and most Walthard nests lacked staining for Müllerian (PAX8 and PAX2) and germ cell tumor markers (SALL4).