We have studied a cohort of renal cell carcinomas (RCCs) with smooth-muscle stroma (N=6), which lacked any of following genetic aberrations: mutations in the VHL-gene-coding sequence, loss of heterozygosity of chromosome 3p, or hypermethylation of VHL. Using targeted next-generation sequencing, no intronic VHL mutations or mutations in selected genes involved in angiogenesis and genes frequently mutated in clear cell RCC were identified. Tumors were also tested for the presence of hotspot mutations in the TCEB1 gene with negative results in all cases. We conclude that there exists a group of RCCs with abundant leiomyomatous stroma, where the epithelial component is indistinguishable from conventional clear cell RCC and distinct from clear cell (tubulo-) papillary RCC and that these tumors lack aberrations related to the function of the VHL gene, mutations in genes involved in angiogenesis, and hotspot mutations in the TCEB1 gene.

Cervical carcinoma is the second most common female malignancy worldwide. It usually spreads by direct local extension or the lymphatic vessels. Hematogenous dissemination with distant skeletal muscle metastases is a rare phenomenon. We report here 2 patients whose recurrent squamous cell carcinomas of the cervix presented with symptomatic skeletal muscle metastases affecting the muscles of the thoracic wall and forearm, respectively. We also discuss the differential diagnosis and comprehensively review the previously published literature on this rare presentation of cervical carcinoma.

Mammary analogue secretory carcinoma (MASC) is a recently described low-grade malignant tumor of the salivary glands, biologically and morphologically equivalent to secretory breast carcinoma. We give a brief overview of this new entity, including morphological, immunohistochemical, molecular-genetic, clinical, epidemiologic features, differential diagnosis, and outcome results.

Germ cell tumors of the testis are a heterogeneous group of neoplasms that affect male adolescents and young adults. Wnt signaling pathway components have been shown to be actively involved in normal and malignant germ cell differentiation and progression. In this study, we aimed to explore the expression patterns of the secreted frizzled‐related protein (SFRP) and Disheveled protein family (DVL) in a subset of testicular germ cell tumors. Eighty‐five formalin‐fixed, paraffin‐embedded tissue samples of the primary germ cell tumors of the testis were stained against SFRP1, SFRP3, DVL1, and DVL2 proteins using immunohistochemistry. SFRP1 and SFRP3 exhibited lower expression in both seminomas and mixed/non‐seminomatous tumors, compared with atrophic/benign tissue (p < 0.001). SFRP3 expression was lower than SFRP1 expression within the seminoma group (p = 0.004), but not within the mixed/non‐seminomatous group (p = 0.409). The majority of the tested cases (27/28, 96%) exhibited low DVL1 protein expression (median 0%, range 0–90%). In contrast, 20 out of 22 tested cases (91%) exhibited strong expression of DVL2 protein (median 80%, range 0–100%). No significant difference in DVL1 and DVL2 protein expression was observed between seminomas and mixed/non‐seminomatous tumors (p = 0.68 and 0.29). The secreted frizzled‐related protein and disheveled protein family members appear to be actively involved in the pathogenesis of primary testicular germ cell tumors.

The characteristic morphologic spectrum of tubulocystic renal cell carcinoma (TC-RCC) may include areas resembling papillary RCC (PRCC). Our study includes 15 RCCs with tubulocystic pattern: 6 TC-RCCs, 1 RCC-high grade with tubulocystic architecture, 5 TC-RCCs with foci of PRCC, 2 with high-grade RCC (HGRCC) not otherwise specified, and 1 with a clear cell papillary RCC/renal angiomyoadenomatous tumor-like component. We analyzed aberrations of chromosomes 7, 17, and Y; mutations of VHL and FH genes; and loss of heterozygosity at chromosome 3p. Genetic analysis was performed separately in areas of classic TC-RCC and in those with other histologic patterns. The TC-RCC component demonstrated disomy of chromosome 7 in 9/15 cases, polysomy of chromosome 17 in 7/15 cases, and loss of Y in 1 case. In the PRCC component, 2/3 analyzable cases showed disomy of chromosome 7 and polysomy of chromosome 17 with normal Y. One case with focal HGRCC exhibited only disomy 7, whereas the case with clear cell papillary RCC/renal angiomyoadenomatous tumor-like pattern showed polysomies of 7 and 17, mutation of VHL, and loss of heterozygosity 3p. FH gene mutation was identified in a single case with an aggressive clinical course and predominant TC-RCC pattern. The following conclusions were drawn: (1) TC-RCC demonstrates variable status of chromosomes 7, 17, and Y even in cases with typical/uniform morphology. (2) The biological nature of PRCC/HGRCC-like areas within TC-RCC remains unclear. Our data suggest that heterogenous TC-RCCs may be associated with an adverse clinical outcome. (3) Hereditary leiomyomatosis-associated RCC can be morphologically indistinguishable from “high-grade” TC-RCC; therefore, in TC-RCC with high-grade features FH gene status should be tested.

To the Editor A 65-year-old woman with a positive family history for breast cancer presented with the palpable mass in the upper outer quadrant of the left breast. Ultrasonography and mammography revealed an oval, hypoechogenic, sharply demarcated mass, measuring 23 9 14 mm, classified as Bi-RADS 4 (Fig. 1A). A core needle biopsy revealed a cellular spindle cell lesion (AE1/AE3 negative) without prominent atypia and mitotic activity (B3 category, Fig. 1B). The multidisciplinary breast meeting discussed the case and recommended a wide local excision of the mass. Grossly, the 20-mm tumor was well-circumscribed, grayish-white on cut section, without necrosis and hemorrhage (Fig. 1C). Histopathologic examination revealed a well circumscribed, spindle cell neoplasm composed of the cells with mild to moderate atypia and sporadic mitotic activity (up to 5/10 hpf mitotic figures, Fig. 1D,E). An extensive immunohistochemical (IHC) examination revealed only convincing S-100 positivity in about 20% of neoplastic cells (Fig. 1F). All other markers were negative (AE1/AE3, Cam5.2, p63, GFAP, SMA, desmin, CD34, HMB-45, SOX-10) while beta-catenin retained cytoplasmic/membranous expression without nuclear positivity. Morphologic and immunohistochemical findings were consistent with a low-grade malignant peripheral nerve sheath tumor (MPNST). Due to the tumor size, clean margins, and the tumor grade, a close follow-up without further treatment of the patient was recommended (1–3). Additional clinical

Renal oncocytoma (RO) may present with a tubulocystic growth in 3% to 7% of cases, and in such cases its morphology may significantly overlap with tubulocystic renal cell carcinoma (TCRCC). We compared the morphologic and immunohistochemical characteristics of these tumors, aiming to clarify the differential diagnostic criteria, which facilitate the discrimination of RO from TCRCC. Twenty-four cystic ROs and 15 TCRCCs were selected and analyzed for: architectural growth patterns, stromal features, cytomorphology, ISUP nucleolar grade, necrosis, and mitotic activity. Immunohistochemical panel included various cytokeratins (AE1-AE3, OSCAR, CAM5.2, CK7), vimentin, CD10, CD117, AMACR, CA-IX, antimitochondrial antigen (MIA), EMA, and Ki-67. The presence of at least focal solid growth and islands of tumor cells interspersed with loose stroma, lower ISUP nucleolar grade, absence of necrosis, and absence of mitotic figures were strongly suggestive of a cystic RO. In contrast, the absence of solid and island growth patterns and presence of more compact, fibrous stroma, accompanied by higher ISUP nucleolar grade, focal necrosis, and mitotic figures were all associated with TCRCC. TCRCC marked more frequently for vimentin, CD10, AMACR, and CK7 and had a higher proliferative index by Ki-67 (>15%). CD117 was negative in 14/15 cases. One case was weakly CD117 reactive with cytoplasmic positivity. All cystic RO cases were strongly positive for CD117. The remaining markers (AE1-AE3, CAM5.2, OSCAR, CA-IX, MIA, EMA) were of limited utility. Presence of tumor cell islands and solid growth areas and the type of stroma may be major morphologic criteria in differentiating cystic RO from TCRCC. In difficult cases, or when a limited tissue precludes full morphologic assessment, immunohistochemical pattern of vimentin, CD10, CD117, AMACR, CK7, and Ki-67 could help in establishing the correct diagnosis.