Chia-Sui Kao

All Publications

• A Clinicopathologic and Molecular Analysis of 34 Mediastinal Germ Cell Tumors Suggesting Different Modes of Teratoma Development AMERICAN JOURNAL OF SURGICAL PATHOLOGY Kao, C., Bangs, C. D., Aldrete, G., Cherry, A. M., Ulbright, T. M. 2018; 42 (12): 1662–73

  View details for Web of Science ID 000450434700010

• A Clinicopathologic and Molecular Analysis of 34 Mediastinal Germ Cell Tumors Suggesting Different Modes of Teratoma Development. The American journal of surgical pathology Kao, C., Bangs, C. D., Aldrete, G., Cherry, A. M., Ulbright, T. M. 2018

  Abstract

  Mediastinal teratomas are enigmatic; those in children and women are almost invariably benign but in men they may be benign or malignant. There are few data on the chromosome 12p status of mediastinal germ cell tumors (GCT), whereas increased 12p copy number is virtually uniform in malignant testicular GCTs. We therefore studied chromosome 12p copy number in 34 diverse mediastinal GCTs and correlated the results with morphology and follow-up to gain insight into possible pathogenesis. Four prepubertal (below 12y) children (3 females and 1 male), 7 postpubertal females (14 to 52y) and 6 postpubertal males (12 to 40y old) had pure, previously untreated teratomas; 15 were mature and 2 had low-grade immaturity. All lacked 12p copy number increase and cytologic atypia, and most (14/17) showed organoid morphology. On follow-up of 16, 1 died of postoperative complications and the remaining 15 were disease free (1 to 119mo, mean: 39mo). Eight postpubertal males (19 to 44y old) had pure teratomas in postchemotherapy resections; 5/8 showed 12p copy number increase. All 8 had distinct cytologic atypia, with organoid morphology in 3. On follow-up, 6 were disease free after surgical resection (1.5 to 94mo, mean 38mo); 1 died of disease at 14.5 months, and 1 was alive with metastases at 176 months. Two postpubertal patients, 1 male (29y) and 1 female (31y), had teratoma with secondary somatic-type malignancies, with positive 12p copy number increase in the former but not the latter. The man's tumor occurred after chemotherapy and was a nonorganoid teratoma with primitive neuroectodermal tumor and malignant glioma; the woman's was a previously untreated organoid teratoma with an undifferentiated carcinoma component. The man died of disease (16mo) and the woman was alive with metastases (27mo). Seven patients had resections for mixed GCTs (4) or pure nonteratomatous tumors, all after chemotherapy; 5/7 had positive 12p copy number increase. The teratoma component of the 2 cases having one showed distinct cytologic atypia and lacked organoid morphology. On follow-up, 1 died of disease (5mo), 2 were alive with disease (1, 1.5mo), 3 were disease free (1 to 43mo; mean: 18mo), and 1 was alive with unknown status (31mo). Our results support that mediastinal teratomas likely develop from 2 separate pathways. Those in children, women and some men arise as pure neoplasms from a nontransformed precursor cell and, therefore, lack 12p copy number increase, show no cytologic atypia, often have organoid morphology and are benign. Common 12p copy number increase, uniform atypia, infrequent organoid structures and malignant behavior support that pure teratomas after chemotherapy in postpubertal males derive from a malignantly transformed precursor cell. Interestingly, we identified organoid pancreatic differentiation only in the benign group and neuroglia more commonly in the malignant teratomas.

  View details for DOI 10.1097/PAS.0000000000001164

  View details for PubMedID 30256256

• Native Kidney Cytomegalovirus Nephritis and Cytomegalovirus Prostatitis in a Kidney Transplant Recipient. Transplant infectious disease : an official journal of the Transplantation Society Tan, S. K., Cheng, X. S., Kao, C., Weber, J., Pinsky, B. A., Gill, H. S., Busque, S., Subramanian, A. K., Tan, J. C. 2018: e12998

  Abstract

  We present a case of cytomegalovirus (CMV) native kidney nephritis and prostatitis in a CMV D+/R- kidney transplant recipient who had completed six months of CMV prophylaxis four weeks prior to the diagnosis of genitourinary CMV disease. The patient had a history of benign prostatic hypertrophy and urinary retention that required self-catheterization to relieve high post-voiding residual volumes. At 7 months post-transplant, he was found to have a urinary tract infection, moderate hydronephrosis of the transplanted kidney, and severe hydroureteronephrosis of the native left kidney and ureter, and underwent native left nephrectomy and transurethral resection of the prostate. Histopathologic examination of kidney and prostate tissue revealed CMV inclusions consistent with invasive CMV disease. This case highlights that CMV may extend beyond the kidney allograft to involve other parts of the genitourinary tract, including the native kidneys and prostate. Furthermore, we highlight the tissue-specific risk factors that preceded CMV tissue invasion. In addition to concurrent diagnoses, health care providers should have a low threshold for considering late-onset CMV disease in high-risk solid organ transplant recipients presenting with signs and symptoms of genitourinary tract pathology. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/tid.12998

  View details for PubMedID 30203504

• Evaluation of Diagnostic Accuracy and a Practical Algorithmic Approach for the Diagnosis of Renal Masses by FNA. Cancer cytopathology Lau, H. D., Kong, C. S., Kao, C. 2018

  Abstract

  BACKGROUND: The classification of renal neoplasms is essential for oncologic risk stratification and clinical management, and an accurate pretreatment pathologic diagnosis can provide useful guidance for active surveillance, minimally invasive ablative therapy, or surgical resection and can reduce the incidence of overtreatment. Previous studies evaluating the diagnostic accuracy of fine-needle aspiration (FNA) and core-needle biopsy (CNB) for renal masses are limited and show variable results.METHODS: Two hundred forty-seven renal FNA cases with or without concurrent CNB performed and/or reviewed at the Stanford University School of Medicine over the course of 20 years were identified. Cytohistopathologic correlation was performed for 77 cases with subsequent resection specimens. All available case materials were reviewed, and select cases were worked up further and reclassified as necessary.RESULTS: Cytohistopathologic correlation showed 96% diagnostic specificity and 83% sensitivity for renal FNA with or without concurrent CNB. Discordant cases were mostly attributed to sampling errors or suboptimal specimens (79%) and also included 2 non-renal cell carcinoma entities (1 case of angiomyolipoma and 1 case of a benign peripheral nerve sheath tumor) and 1 case involving misclassification of the renal cell carcinoma subtype.CONCLUSIONS: There is considerable value in FNA/CNB for the initial diagnosis of renal masses because of the high diagnostic specificity and sensitivity. Sensitivity is predominantly dependent on sufficient sampling, and additional potential diagnostic pitfalls include nonepithelial and rare entities. Judicious use of ancillary techniques is encouraged, especially when one is presented with a limited specimen, and this article presents a practical algorithmic approach to the diagnosis of renal masses using salient morphologic features and results from ancillary studies. Fine-needle aspiration is an accurate method for the diagnosis of renal masses. A practical diagnostic algorithm, based on salient morphologic and ancillary findings, is presented.

  View details for DOI 10.1002/cncy.22037

  View details for PubMedID 30193011

• Adrenal Myelolipomas Involved by Plasma Cell Myeloma. American journal of clinical pathology Lin, C., Levy, D., Higgins, J. P., Kunder, C. A., Kao, C. 2018

  Abstract

  Objectives: To report the presence and evaluate the frequency of plasma cell neoplasms within adrenal myelolipomas.Methods: Adrenal myelolipomas within our institution were reviewed for the presence of hematologic neoplasia, and a review of the literature was performed.Results: Two (9%) of 23 adrenal myelolipomas were involved by plasma cell myeloma. The patients were 71 and 81 years old, one woman and one man, with tumors measuring 7 cm and 8.5 cm, respectively. Both tumors contained large aggregates of dysplastic plasma cells occupying at least one *10 field and demonstrated light chain restriction. Neither had an established diagnosis of plasma cell neoplasm previously. After receiving therapy, one patient exhibited a stable clinical course 1 year after diagnosis while the other died of disease 3 years later.Conclusions: We report the first two cases of adrenal myelolipoma involved by plasma cell myeloma, a rare and subtle finding that has significant clinical implications.

  View details for DOI 10.1093/ajcp/aqy068

  View details for PubMedID 30052719

• Evaluation of Diagnostic Accuracy and a Practical Algorithmic Approach for the Diagnosis of Renal Masses by Fine Needle Aspiration Lau, H., Kong, C., Kao, C. NATURE PUBLISHING GROUP. 2018: 155

  View details for Web of Science ID 000429308601077

• Clinicopathologic Characteristics of Fumarate Hydratase-Deficient and Hereditary Leiomyomatosis and Renal Cell Carcinoma-Associated Renal Cell Carcinoma: A Series of 10 Cases Lau, H., Williamson, S. R., Kunder, C., Fan, A. C., Kao, C. NATURE PUBLISHING GROUP. 2018: 358

  View details for Web of Science ID 000429308602336

• Do Nonseminomatous Germ Cell Tumors of the Testis With Lymphovascular Invasion of the Spermatic Cord Merit Staging as pT3? AMERICAN JOURNAL OF SURGICAL PATHOLOGY Gordetsky, J., Sanfrancesco, J., Epstein, J. I., Trevino, K., Xu, H., Osunkoya, A., Xiao, G. Q., Kao, C., Unger, P., Hashemi-Sadraei, N., Albany, C., Jorns, J. M., Lu, D. Y., Matoso, A., Rais-Bahrami, S., Schwartz, L. E., Ulbright, T. M., Idrees, M. T. 2017; 41 (10): 1397–1402

  Abstract

  The staging of testicular nonseminomatous germ cell tumors (NSGCTs) with lymphovascular invasion (LVI) of the spermatic cord in the absence of cord parenchymal involvement remains controversial. Our previous study showed that tumors with spermatic cord LVI present at a higher clinical stage than tumors with LVI confined to the testis (pT2). We compared NSGCTs with LVI of the spermatic cord without direct involvement of the spermatic cord soft tissues to pT3 tumors to help clarify the appropriate staging of this histologic finding. A retrospective, multi-institutional review was performed to identify cases of NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord. The clinical-pathologic findings were compared with NSGCTs with spermatic cord soft tissue invasion (pT3). We identified 38 pT2 NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord and 89 pT3 tumors. There were no significant differences in patient age, tumor size, or clinical stage at presentation between the 2 groups. There were no significant differences in dominant histologic subtype, rete testis invasion, hilar soft tissue invasion, or margin status. There were no significant differences in disease recurrence/progression (P=0.63), recurrence/progression after chemotherapy (P=0.35), or death (P=0.51) between patients with only spermatic cord LVI versus patients with cord soft tissue invasion. In patients with pT2 NSGCTs according to the current staging, LVI in the spermatic cord without cord soft tissue invasion is comparable with pT3 tumors in terms of clinical stage at presentation as well as disease recurrence and survival.

  View details for Web of Science ID 000410661700010

  View details for PubMedID 28719463

• Variant morphology in upper urinary tract urothelial carcinoma: a fourteen-year case series of biopsy and resection specimens. Human pathology Hayashi, H., Mann, S., Kao, C., Grignon, D., Idrees, M. T. 2017

  Abstract

  Upper urinary tract urothelial carcinoma exhibiting variant morphology, especially in higher-grade tumors, is a recognized phenomenon but has not been comparatively studied in biopsy versus resection material. We studied the morphologic patterns and clinicopathological features, and provide a comparison between biopsy and resection specimens. Consultation cases were evaluated separately to investigate for possible consultation bias. A total of 383 in-house cases from 352 patients including 314 resection specimens and 69 biopsies from 2001-2014 were reviewed from a single institution. Histologic type, tumor grade, invasion, pathologic stage, nodal status, metastasis, and the presence and type of variant morphology for each case were evaluated. Variant morphology was identified in 5 biopsy specimens (7.2%) and 42 resection specimens (13.4%). The most common variant morphologic pattern was squamous differentiation (16 cases, 4.5%) followed by an inverted growth pattern (8 cases, 2.2%). The presence of variant morphology in resection specimens had a significant association with higher tumor grade, higher pT stage, and non-papillary configuration. Out of 69 patients with biopsies, 31 had a subsequent resection. In comparison, 181 consultation cases from 168 patients showed variant morphology in six biopsies (7.1%) and twenty-seven resections (28.1%). In conclusion, the frequency of recognizing variant morphology in biopsies is about one-half of that in resections. The inclusion of consultation cases can inflate the incidence of variant morphology. As a result, the frequency of variant morphology in our in-house cases is lower than the percentage reported in the literature, most likely secondary to a consultation bias.

  View details for DOI 10.1016/j.humpath.2017.05.001

  View details for PubMedID 28506733

• Immunohistochemical Assessment of 23 Immature Ovarian Teratomas Charville, G., Longacre, T., Vogel, H., Ulbright, T. M., Kao, C. NATURE PUBLISHING GROUP. 2017: 279A–280A

  View details for Web of Science ID 000394467301400

• Plasmacytoid Urothelial Carcinoma: A Single Institution Immunohistochemical and Molecular Study of 26 Cases Perrino, C., Cheng, L., Idrees, M., Eble, J. N., Kao, C., Grignon, D. NATURE PUBLISHING GROUP. 2017: 248A

  View details for Web of Science ID 000393724401277

• A Comparative Study of pT3 versus pT2 Testicular Germ Cell Tumors, Including Evaluation of Lymphovascular Invasion (LVI) in the Spermatic Cord Sanfrancesco, J., Trevino, K., Osunkoya, A., Xiao, G. Q., Kao, C., Gordetsky, J., Unger, P., Ulbright, T. M., Idrees, M. NATURE PUBLISHING GROUP. 2017: 255A–256A

  View details for Web of Science ID 000393724401306

• A Clinicopathologic and Molecular Analysis of 34 Mediastinal Germ Cell Tumors (GCT) Supporting a Dual Histogenesis for Teratomas Kao, C., Bangs, D., Ulbright, T. M. NATURE PUBLISHING GROUP. 2017: 482A

  View details for Web of Science ID 000393724402420

• Plasmacytoid Urothelial Carcinoma: A Single Institution Immunohistochemical and Molecular Study of 26 Cases Perrino, C., Cheng, L., Idrees, M., Eble, J. N., Kao, C., Grignon, D. NATURE PUBLISHING GROUP. 2017: 248A

  View details for Web of Science ID 000394467301277

• A Comparative Study of pT3 versus pT2 Testicular Germ Cell Tumors, Including Sanfrancesco, J., Trevino, K., Osunkoya, A., Xiao, G. Q., Kao, C., Gordetsky, J., Unger, P., Ulbright, T. M., Idrees, M. NATURE PUBLISHING GROUP. 2017: 255A–256A

  View details for Web of Science ID 000394467301306

• A Clinicopathologic and Molecular Analysis of 34 Mediastinal Germ Cell Tumors (GCT) Supporting a Dual Histogenesis for Teratomas Kao, C., Bangs, D., Ulbright, T. M. NATURE PUBLISHING GROUP. 2017: 482A

  View details for Web of Science ID 000394467302511

• Immunohistochemical Assessment of 23 Immature Ovarian Teratomas Charville, G., Longacre, T., Vogel, H., Ulbright, T. M., Kao, C. NATURE PUBLISHING GROUP. 2017: 279A–280A

  View details for Web of Science ID 000393724401400

• Evidence of a dual histogenetic pathway of sacrococcygeal teratomas HISTOPATHOLOGY Emerson, R. E., Kao, C., Eble, J. N., Grignon, D. J., Wang, M., Zhang, S., Wang, X., Fan, R., Masterson, T. A., Roth, L. M., Cheng, L. 2017; 70 (2): 290-300

  Abstract

  Sacrococcygeal teratomas are rare tumours that occur most frequently in neonates, although adult cases also occur. The molecular pathogenesis of these tumours and their long-term prognosis is uncertain. We investigated the i(12p) status of a large number of primary sacrococcygeal teratomas in both children and adults, including cases with malignant germ cell tumour elements.Fifty-four sacrococcygeal teratoma specimens from 52 patients were identified, and available follow-up information was obtained. Fluorescence in-situ hybridization analysis was performed to identify isochromosome 12p [i(12p)] abnormalities on paraffin blocks of the tumours. Among the 48 paediatric patients, there were 44 teratomas and four tumours with combined teratoma and yolk sac tumour (one of whom also had primitive neuroectodermal tumour). The teratomas included 37 mature teratomas and 11 immature teratomas (four grade 1, two grade 2, and five grade 3). The 44 teratomas lacking a yolk sac tumour component were all negative for i(12p). The four tumours with a yolk sac tumour component were all positive for i(12p). The four adult cases all lacked non-teratomatous germ cell tumour components, immature elements, and i(12p). Follow-up information was available for 32 patients. Two patients with teratoma had recurrence, but were alive with no evidence of disease after long-term follow-up. One patient with combined teratoma and yolk sac tumour had recurrence 7 months after resection. The other patients were alive with no evidence of disease at last follow-up.Our data suggest that paediatric sacrococcygeal teratomas should be considered as two distinct groups with divergent histogenetic pathways. The prognosis of these tumours is excellent, despite rare recurrence.

  View details for DOI 10.1111/his.13062

  View details for Web of Science ID 000394982000017

• "Dissecting Gonadoblastoma" of Scully: A Morphologic Variant That Often Mimics Germinoma. American journal of surgical pathology Kao, C., Idrees, M. T., Young, R. H., Ulbright, T. M. 2016; 40 (10): 1417-1423

  Abstract

  Dr Robert E. Scully, who recognized and defined gonadoblastoma (GB), used the term "dissecting gonadoblastoma" (DGB) to describe variants with either an infiltrative type or diffuse pattern instead of the usual small nested arrangement. These patterns have not been emphasized in the literature. To investigate the features of DGB we examined 50 GBs microscopically and performed immunohistochemistry (IHC) in some. DGB was found in 38 (76%) GBs and was represented by 3 patterns. The most frequent was solid/expansile (n=26), consisting of large coalescent nests of germ cells, often (92%) interrupted by fibrovascular septa, with usually minor numbers of sex cord cells. Less frequent were small anastomosing nests (n=24) and cord-like arrangements (n=22) of germ cells irregularly distributed in a prominent stroma and with mostly inconspicuous sex cord cells. Most DGBs (24) showed >1 pattern and demonstrated the characteristic globular deposits of basement membrane, although these were often subtle. The germ cells in all patterns varied from spermatogonium-like to seminoma-like; OCT3/4 was positive only in the latter (7/7). The sex cord cells were small with dense, oval or angulated nuclei, inconspicuous nucleoli, and positivity for inhibin (9/9, strong), FOXL2 (9/9, strong), SF1 (8/9, strong), SOX9 (9/9, weak and focal), WT1 (5/7, variable), and calretinin (3/7, variable). Granulomas were present in 84% of germinoma foci, 13% of DGB foci, and 8% of classic GB foci. Twenty two of 38 DGBs had associated germinoma; 3 also had embryonal carcinoma, yolk sac tumor, and choriocarcinoma, respectively. Follow-up of 2 cases lacking an invasive tumor showed that both patients were disease free at 13 and 4.8 years after bilateral gonadectomy. We conclude that DGB is commonly seen with classic GB and displays identical IHC features, supporting it as a morphologic variant of GB. It appears likely that cord-like DGB is the earliest phase in a GB developmental continuum that may proceed successively into anastomosing, nested (classic GB), and solid/expansile patterns. DGB often mimics germinoma because of the large size of the nests, pseudoinfiltrative pattern of some cases, and inconspicuous sex cord cells. The presence of sex cord cells (identification aided by IHC for sex cord markers), the heterogenous morphology of the germ cells, and globules of basement membrane are useful differential features. The lack of a granulomatous reaction also favors DGB over germinoma. Mistaking DGB for GB with invasive germinoma may result in more aggressive therapy than warranted. The likely relationship of DGB to the relatively recently described concept of so-called "undifferentiated gonadal tissue" is discussed herein.

  View details for DOI 10.1097/PAS.0000000000000704

  View details for PubMedID 27454939