Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome that results in renal phosphate wasting with hypophosphatemia. In most cases, the underlying cause of TIO is a small mesenchymal ...neoplasm that is often difficult to detect, resulting in delayed diagnosis. One such neoplasm is the phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT), an unusual entity with unique morphologic and biochemical features. Most of these tumors are found at appendicular sites with only rare cases reported in the jaws. We describe a PMTMCT involving the mandible in a patient with a protracted history of osteomalacia. A review of the current literature is provided with emphasis on the clinical and histologic features, etiopathogenesis, and management of PMTMCT in the setting of TIO.
We present a case of a patient who was initially diagnosed with poorly differentiated prostatic adenocarcinoma on prostate needle core biopsy. Upon staging workup, a computed tomographic scan showed ...a 9-cm left renal mass involving mainly the pelvicalyceal system. Positron emission tomographic scan showed increased uptake in para-aortic, paracaval, and retrocaval lymph nodes suspicious for metastatic disease. Left nephrectomy revealed involvement with extranodal Rosai-Dorfman disease. Lymphadenectomy revealed metastatic prostatic adenocarcinoma; however, the lymph nodes did not show evidence of Rosai-Dorfman disease. Isolated involvement of the kidney by Rosai-Dorfman disease is very rare. The combination of prostatic adenocarcinoma and isolated extranodal Rosai-Dorfman disease of the kidney makes this case unique.
Cryoablation is an acceptable treatment option for small renal cortical neoplasms (RCN). Unlike extirpative interventions, intraoperative needle biopsy is the only pathologic data for ablated tumors. ...It is imperative that sampled tissue accurately captures pathology. We studied the optimal intraoperative needle core biopsy protocol for small RCN during laparoscopic renal cryoablation (LCA).
Patients with RCN<4cm underwent intraoperative biopsy during LCA. Four biopsy cores were taken per tumor, 2 before and 2 after LCA by using both a standard and modified technique. Standard technique: needle biopsy device was deployed after insertion into the renal tissue at a depth of 5mm. Modified technique: needle biopsy device was deployed 1mm outside of the renal tissue. Biopsies were examined and compared with reference standard pathology. Percentage agreement was calculated across biopsy types (standard vs. modified) and time points (pre- vs. postcryoablation). Logistic regression was used to identify factors impacting biopsy accuracy.
Thirty patients with 33 RCNs underwent LCA. The mean patient age was 69.1±8.0yrs, and mean tumor size was 2.3±0.7cm. No significant bleeding resulted from biopsies. A definitive diagnosis was made in 31/33 RCNs (94.0%). Ten tumors (30.3%) were benign, 21 (63.7%) were malignant, and 2 (6.0%) were nondiagnostic. Biopsy length was significantly longer using the standard vs. modified technique with mean lengths of 9.3mm vs. 7.0mm, respectively (P=.02). Highest agreement was seen in preablation biopsies (90.3%). A significant association with agreement was seen for younger age (P=.05) and larger tumor size (P=.02).
Younger age and larger tumor size were associated with improved accuracy. Preoperative sampling resulted in superior accuracy and the standard technique resulted in significantly longer cores. Use of preablation standard biopsy technique may result in the most accurate pathologic diagnosis for patients undergoing cryoablation for small RCNs.
The presence of estrogen and progesterone-receptor-positive stroma is well known in renal mixed epithelial and stromal tumor, cystic nephroma, and angiomyolipoma with epithelial cysts. It has been ...suggested that the hormone receptor positivity in mixed epithelial and stromal tumor may be etiologically related to exogenous hormone intake-a phenomenon that has become more frequent in recent years. In the past few years, we have observed such stroma in some non-neoplastic kidneys, as well as in tumor-bearing kidneys away from the tumor. Herein we present our experience with 10 such cases. In a prospective manner, whenever we noted stroma resembling that in ovaries or müllerian organs (endometrial or cervical-like) in kidneys removed for any cause, immunohistochemical stains for estrogen and progesterone receptors were performed. There were eight males and two females among the group, with ages ranging from 11 months to 71 years. In six cases, the nephrectomies were performed for a non-functional kidney, and in three for tumors (one each of chromophobe, clear cell, and acquired cystic disease-associated renal cell carcinoma). One case was a partial nephrectomy for vesico-ureteric reflux, with upper pole hydronephrosis. Such stroma was present in nine cases as a non-mass forming proliferation around dilated, frequently inflamed pelvicalyceal system and collecting ducts. In one it was present at the periphery of an acquired cystic disease-associated renal cell carcinoma, as well as around non-tumorous cysts. The only common finding in all cases was a generalized or segmental hydronephrosis, or tumor compression-related focal obstruction. The stroma was positive for estrogen receptors in all 10 cases, and for progesterone receptors in seven. Thus, estrogen- and progesterone receptor-positive stroma can be present in the kidney, not only as a component of certain tumors, but also in association with non-neoplastic conditions. Its association with obstructive changes suggests that it may represent a metaplastic change in the renal interstitial cells surrounding these obstructed epithelial structures.
Aims
The 2022 WHO classification for kidney tumours recently downgraded clear cell tubulopapillary (also known as clear cell papillary) renal cell carcinoma (RCC) to a benign neoplasm (i.e. clear ...cell tubulopapillary renal cell tumour) based on the overwhelmingly banal nature of this neoplasm. However, it has been recognized that some clear cell tubulopapillary renal cell tumours demonstrate vascular, adipose or pelvicalyceal invasion, raising the possibility of more aggressive behaviour. The goal of this study was to determine if these ‘high stage’ features have an effect on tumour prognosis, warranting a carcinoma designation.
Methods and Results
After excluding cases with tissue artefact (i.e. prior core biopsy track changes) and other RCC subtypes with next‐generation sequencing, nine clear cell tubulopapillary renal cell tumours with these so‐called ‘high stage’ features, and otherwise classic morphologic and immunophenotypic findings, including low‐grade cytology and ‘cup‐like’ CA9 expression, were evaluated. Median tumour size was 2.2 cm with a range of 0.8 to 6.7 cm. Eight cases (89%) demonstrated perinephric or hilar adipose tissue invasion, although most of these cases showed a bulging (in contrast to an infiltrative) growth pattern. One case demonstrated renal vascular invasion in addition to hilar adipose tissue invasion, and one case demonstrated extension into the pelvicalyceal system. There were no recurrences or evidence of metastatic disease.
Conclusion
These overall findings continue to support the benign designation for clear cell tubulopapillary renal cell tumours, despite morphologic features that might raise the possibility of a ‘higher stage’ neoplasm.
Specimens from the prostate and bladder are commonly encountered by the general surgical pathologist. Emphasis is usually placed on neoplasms of the bladder and prostate, particularly if malignant, ...owing to their therapeutic consequences. A good command of benign lesions occurring in the bladder and prostate, and knowledge of their preneoplastic potential will help pathologists confidently diagnose malignancy versus its benign mimickers and guide the urologists in choosing the appropriate therapy and follow-up for the patient.
To present a mixture of benign entities, and discuss their histologic and clinical characteristics, hoping to provide a practical review for the general surgical pathologist.
An extensive review of the literature on the entities discussed was performed.
A wide variety of benign entities are present in the prostate and bladder. Benign lesions in the prostate can be age related, such as prostatic atrophy and benign prostatic hyperplasia; transition zone associated, such as basal cell hyperplasia, adenosis, and sclerosing adenosis; or prostatic urethra associated. Benign lesions of the bladder encompass a wide variety of reactive changes that can occur in the urothelium, as well as hyperplastic lesions or reactive proliferations that could be misdiagnosed as malignant. The bladder responds to chronic irritation through several reactive/metaplastic lesions such as cystitis cystica/glandularis, keratinizing squamous metaplasia, or nephrogenic metaplasia. The urothelium can also give rise to hyperplastic/proliferative lesions, in particular von Brunn nest hyperplasia, papillary polypoid cystitis, and pseudocarcinomatous proliferation, which should be distinguished from malignant processes. Ectopic tissue, such as prostatic or mullerian, can also be seen.
Trophoblastic differentiation (including choriocarcinoma) arising in urothelial carcinoma has been described in numerous case reports, but never in a single series. We present a series of these ...tumors, describing the morphologic spectrum, applying traditional and novel immunohistochemical stains, and characterizing clinical follow-up. We identified 16 cases, arising predominantly in the bladder (N=14), but also the ureter (N=1) and prostatic urethra (N=1). Six of our cases (38%) contained invasive urothelial carcinoma with admixed syncytiotrophoblasts, 8 cases (50%) consisted of invasive urothelial carcinoma with choriocarcinoma, 1 case (6%) showed urothelial carcinoma in situ with associated choriocarcinoma, and 1 case (6%) consisted of pure choriocarcinoma. Other subtypes of variant morphology were seen in 5 of our cases (31%) and included squamous, glandular, lipoid, chordoid/myxoid, and sarcomatoid features. Given the limited specificity of human chorionic gonadotropin immunohistochemistry, we also studied the expression of a novel specific trophoblastic marker, hydroxyl-δ-5-steroid dehydrogenase, as well as Sal-like protein 4. Human chorionic gonadotropin expression was seen in nearly all cases (93%) but was often not limited to the trophoblastic component, staining the urothelial component also in 85% of the cases. Expression of hydroxyl-δ-5-steroid dehydrogenase was more sensitive and more specific, staining 100% of the cases and limited to trophoblasts in all but 1 case. Sal-like protein 4 expression was variable, staining trophoblast in only 50% of cases and staining the urothelial carcinoma component in 43% of those positive cases. Most of our tumors presented at a high stage and were associated with poor clinical outcomes, with at least muscle-invasive disease (pT2) in 10 of the 14 bladder tumors (71%), periureteric fat invasion in the ureter tumor (pT3), distant metastases in 7 of 16 cases (44%) and death of disease in 3 of the 15 patients with follow-up (20%). Our study describes a series of urothelial carcinomas with trophoblastic differentiation, demonstrating the morphologic spectrum of this entity, its frequent association with other subtypes of variant morphology, its characteristic immunoprofile, and its aggressive clinical behavior.
Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an ...online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive
fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required
FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.
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