OBJECTIVES:Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC. METHODS:It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists. RESULTS:Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3). Among all 3 groups, group 1 was most likely to diagnose concomitant CIS and PUC in the same specimen but in different tissue fragments (58%). Pagetoid spread was reported to favor CIS predominantly by group 1 (61%). Urologists felt that the term lateral spread/shoulder was unclear (75%) and preferred early PUC (44%) or PUC with early growth (44%). Half (53%) of urologists felt that reporting CIS instead of lateral spread of PUC would change management. CONCLUSIONS:Documentation of flat lesions lacks consensus among pathologists and may benefit from standardized terminology. Moreover, the distinction between CIS and early or lateral spread of PUC is not always clear to urologists and can influence disease management.

Soft tissue tumors are rare mesenchymal tumors with divergent differentiation. The diagnosis of soft tissue tumors is challenging for pathologists owing to the diversity of tumor types and histological overlap among the tumor entities. Present-day understanding of the molecular pathogenesis of soft tissue tumors has rapidly increased with the development of molecular genetic techniques (e.g., next-generation sequencing). Additionally, immunohistochemical markers that serve as surrogate markers for recurrent translocations in soft tissue tumors have been developed. This review aims to provide an update on recently described molecular findings and relevant novel immunohistochemical markers in selected soft tissue tumors.

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare superficial mesenchymal tumor. SCPFT has a distinctive morphologic appearance, marked by significant nuclear pleomorphism, low mitotic rate, and diffuse CD34 positivity. SCPFT is underdiagnosed because of its rarity and misdiagnosis as sarcoma, with very few reported cases of local recurrence or metastasis. Recognition and awareness of SCPFT are essential for accurate diagnosis and appropriate clinical management. We describe here the case of a 37-year-old male who presented with a right calf mass diagnosed as SCPFT with subsequent local recurrence of the tumor.

CONTEXT.—:Grade Group assessed using Gleason combined score and tumor extent is a main determinant for risk stratification and therapeutic planning of prostate cancer.OBJECTIVE.—:To develop a 3-dimensional magnetic resonance imaging (MRI) model regarding Grade Group and tumor extent in collaboration with uroradiologists and uropathologists for optimal treatment planning for prostate cancer.DESIGN.—:We studied the data from 83 patients with prostate cancer who underwent multiparametric MRI and subsequent MRI-transrectal ultrasound fusion biopsy and radical prostatectomy. A 3-dimensional MRI model was constructed by integrating topographic information of MRI-based segmented lesions, biopsy paths, and histopathologic information of biopsy specimens. The multiparametric MRI-integrated Grade Group and laterality were assessed by using the 3-dimensional MRI model and compared with the radical prostatectomy specimen.RESULTS.—:The MRI-defined index tumor was concordant with radical prostatectomy in 94.7% (72 of 76) of cases. The multiparametric MRI-integrated Grade Group revealed the highest agreement (weighted κ, 0.545) and a significantly higher concordance rate (57.9%) than the targeted (47.8%, P = .008) and systematic (39.4%, P = .01) biopsies. The multiparametric MRI-integrated Grade Group showed significantly less downgrading rates than the combined biopsy (P = .001), without significant differences in upgrading rate (P = .06). The 3-dimensional multiparametric MRI model estimated tumor laterality in 66.2% (55 of 83) of cases, and contralateral clinically significant cancer was missed in 9.6% (8 of 83) of cases. The tumor length measured by multiparametric MRI best correlated with radical prostatectomy as compared with the biopsy-defined length.CONCLUSIONS.—:The 3-dimensional model incorporating MRI and MRI-transrectal ultrasound fusion biopsy information easily recognized the spatial distribution of MRI-visible and MRI-nonvisible cancer and provided better Grade Group correlation with radical prostatectomy specimens but still requires validation.

We report a 38-year-old female with a history of primary pelvic PEComa and subsequent metastatic PEComa to the mediastinum who presented with recurrent mediastinal metastasis in April 2021. At initial presentation in 2010, the patient reported a three-month history of abdominal pain, hot flashes, night sweats, and a one-day history of bloating. Surgery revealed an 18-cm multilobulated pelvic mass involving the posterior uterus, bladder, and bilateral adnexa. Histology showed spindled and epithelioid tumor cells immunopositive for HMB-45, desmin, TFE3, SMA, caldesmon, Melan-A and calretinin. Cytokeratin, S-100, inhibin, myogenin, and OCT3/4 immunostains were negative. In 2013 the patient re-presented with chest pain. Imaging confirmed a mediastinal mass involving the pericardium with histology resembling the previous pelvic mass. Following initial resection and mTOR therapy, the mediastinal mass recurred once in 2015 with similar histologic findings. This case provides the first description of a malignant pelvic PEComa metastasizing to the mediastinum, and demonstrates the challenges associated with diagnosing metastatic PEComa. Though malignant PEComa with metastasis to the mediastinum is rare, it is important to recognize the natural process of this tumor to ensure adequate follow-up and patient care.

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare mesenchymal tumor of borderline malignancy. It generally involves superficial soft tissue, with a predilection to the lower extremities. Microscopically this tumor is characterized by a fascicular and storiform growth pattern, spindled to epithelioid cells, nuclear atypia with pleomorphism, and eosinophilic granular, and fibrillar to glassy cytoplasm. Strong diffuse immunoreactivity for CD34 is very characteristic of this entity. Due to under-recognition, this tumor is generally underreported. Additionally, cases of recurrence are rarely reported in the literature. We will comprehensively review the English language literature on all reported cases of SCPFT, with emphasis on recurrence.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver carcinoma displaying both hepatocytic and cholangiocytic differentiation within the same tumor. Relative to classic hepatocellular carcinoma (HCC), cHCC-CCA has more aggressive behavior and a poorer prognosis. Though recent advances have improved our understanding of the biology underlying cHCC-CCAs, they remain diagnostically challenging for pathologists because of their morphologic and phenotypic diversity. Accurate diagnosis of cHCC-CCA is important for patient management and prognostication. Herein, we review recent updates on cHCC-CCA, focusing on tumor classification, pathology, and diagnostic approach.

Background. Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods. Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results. A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion. There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland.

Gastric adenomyoma is a rare tumor composed of smooth muscle fibers and glandular tissue. Usual presentations include nausea, bloating, and gastric outlet obstruction. We describe a case of a 60-year-old woman who presented with abdominal pain and melena. Endoscopy showed a 1.5 cm polyp in the stomach body that was resected using snare polypectomy. Biopsy showed glands mixed with fibromuscular tissue consistent with gastric adenomyoma. We conclude that gastric adenomyoma, although rare, may present as a bleeding polyp in the stomach body and may be treated with excisional polypectomy.

Granulomatous lesions in the breast are uncommon, have a variety of etiologies, and may mimic malignancies on clinical, radiologic, and histopathologic examination. We present two cases of post-biopsy granulomatous reaction mimicking ductal carcinoma in situ (DCIS): in a 67-year-old female who underwent mastectomy for DCIS and a 73-year-old female with a history of invasive ductal carcinoma who underwent excisional biopsy for an incompletely excised radial scar. On microscopic examination, the area of the previous biopsy sites contained a circumscribed proliferation of epithelioid cells surrounding collections of acellular pale eosinophilic material, resembling DCIS with comedo necrosis. Immunohistochemical staining demonstrated that the epithelioid cells were immunoreactive for CD68 and negative for cytokeratin (AE1/AE3). There was absent expression of the myoepithelial markers p63 and smooth muscle myosin heavy chain around the cells. The light microscopic and immunohistochemical findings were supportive of a granulomatous process rather than DCIS. These cases demonstrate an unusual presentation of exuberant biopsy site-related granulomatous reaction morphologically mimicking DCIS, and underscore the need for careful histopathologic examination with ancillary immunohistochemical testing in distinguishing granulomatous processes from malignancies.

Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.

The presence of a cribriform pattern is now recognized as a clinically important, independent adverse prognostic indicator for prostate cancer. For this reason the International Society of Urological Pathology (ISUP) recently recommended its inclusion in standard reporting. In order to improve interobserver agreement as to the diagnosis of cribriform patterns, the ISUP assembled an international panel of 12 expert urogenital pathologists for the purpose of drafting a consensus definition of cribriform pattern in prostate cancer, and provide their opinions on a set of 32 images and on potential diagnostic criteria. These images were selected by the 2 nonvoting convenors of the study and included the main categories where disagreement was anticipated. The Delphi method was applied to promote consensus among the 12 panelists in their review of the images during 2 initial rounds of the study. Following a virtual meeting, convened to discuss selected images and diagnostic criteria, the following definition for cribriform pattern in prostate cancer was approved: "A confluent sheet of contiguous malignant epithelial cells with multiple glandular lumina that are easily visible at low power (objective magnification ×10). There should be no intervening stroma or mucin separating individual or fused glandular structures" together with a set of explanatory notes. We believe this consensus definition to be practical and that it will facilitate reproducible recognition and reporting of this clinically important pattern commonly seen in prostate cancer. The images and the results of the final Delphi round are available at the ISUP website as an educational slide set (https://isupweb.org/isup/blog/slideshow/cribriform-slide-deck/).

Background: Rosai-Dorfman disease (RDD) is a rare entity characterized by lymphadenopathy with dilated lymph node sinuses containing lymphocytes, plasma cells, and histiocytes exhibiting emperipolesis. IgG4-related disease (IgG4-RD) is relatively more common and is characterized by mass-forming lesions with dense lymphoplasmacytic infiltration, numerous IgG4 positive cells, fibrosis which is at least focally storiform, and obliterative phlebitis. Concomitant RDD and IgG4-RD is rare, and the significance of this association remains unclear. Case presentation: A 64-year-old female presented with the gradual onset of a painful right gluteal mass. The mass was clinically suspected to represent an infected sebaceous cyst and was surgically resected. Histological examination revealed a mixed inflammatory reaction in adipose tissue. There were areas of histiocytic proliferation with phagocytosis of inflammatory cells (emperipolesis), predominantly lymphocytes and plasma cells. There was also prominent storiform sclerosis with dense collections of plasma cells. No obliterative thrombophlebitis was seen. Immunohistochemical staining highlighted S100-positive cells with emperipolesis, greater than 50 IgG4 positive cells per high power field, and an IgG4/IgG ratio of greater than 40%. The histologic and immunohistochemical findings were those of RDD with concomitant IgG4-RD. Conclusions: There is limited literature on RDD with increased IgG4-positive plasma cells; and the exact relationship and clinical significance of this finding remains undetermined. We present here a case with combined RDD and IgG4-RD and review the relevant literature.

Mediastinal germ cell tumors (MGCTs) are the most common extragonadal germ cell tumors (GCTs) and most often arise in the anterior mediastinum with a male predilection. MGCTs also have a predilection for patients with Klinefelter syndrome and possibly other genetic conditions. MGCTs, as GCTs at other extragonadal sites, are thought to arise from germ cells improperly retained during migration along the midline during embryogenesis. Similar to their counterparts in the testes, MGCTs are classified into seminomatous and nonseminomatous GCTs. Seminomatous MGCT represents pure seminoma, whereas nonseminomatous MGCTs encompass pure yolk sac tumors, embryonal carcinoma, choriocarcinoma, mature or immature teratoma, and mixed GCTs with any combination of GCT types, including seminoma. Somatic-type or hematologic malignancies can also occur in association with a primary MGCT. MGCTs share molecular findings with GCTs at other sites, most commonly the presence of chromosome 12p gains and isochromosome i(12p). Treatment includes neoadjuvant chemotherapy followed by surgical resection of residual tumor, with the exception of benign teratomas, which require only surgical resection without chemotherapy. In this review, we highlight and provide an update on pathologic, clinical, and molecular features of MGCTs. Immunohistochemical profiles of each tumor type, as well as differential diagnostic considerations, are discussed.

Mesenchymal tumors of the mediastinum are a heterogenous group of rare tumors with divergent lineages. Mediastinal mesenchymal tumors are diagnostically challenging due to their diversity and morphologic overlap with nonmesenchymal lesions arising in the mediastinum. Accurate histologic diagnosis is critical for appropriate patient management and prognostication. Many mediastinal mesenchymal tumors affect distinct age groups or occur at specific mediastinal compartments. Neurogenic tumors, liposarcoma, solitary fibrous tumor, and synovial sarcoma are common mesenchymal tumors in the mediastinum. Herein, we provide an update on the diagnostic approach to mediastinal mesenchymal tumors and a review of the histologic features and differential diagnosis of common benign and malignant mesenchymal tumors of the mediastinum.