Pathologic Complete Response to Neoadjuvant Chemotherapy and Pembrolizumab in Postpartum High-Risk Basal-Type Breast Cancer.

Neoadjuvant chemoimmunotherapy with pembrolizumab now defines the standard of care for early high-risk triple-negative breast cancer (TNBC). However, the role of pembrolizumab in neoadjuvant therapy (NAT) for estrogen receptor-positive (ER+) breast cancer remains uncertain. A 39-year-old G2P2 female discovered a palpable mass in the right breast while breastfeeding her 7-month-old child, leading to the diagnosis of a high-grade ER+ (80% moderate staining), human epidermal growth factor receptor 2-negative (ErbB2-) invasive ductal carcinoma with axillary nodal involvement. Gene expression profiling with the MammaPrint 70-gene signature and BluePrint 80-gene signature revealed a tumor with high-risk, basal-type biology. The multidisciplinary breast cancer team recommended NAT with pembrolizumab, carboplatin, paclitaxel, doxorubicin, and cyclophosphamide. Within six weeks, the patient exhibited a remarkable response, with no palpable mass or lymph node, and post-treatment examinations confirmed a complete clinical and radiologic response. The patient underwent lumpectomy and sentinel lymph node biopsy, revealing a pathological complete response with minimal ductal carcinoma in situ and negative axillary nodes. Adjuvant radiation therapy was administered, and the patient completed adjuvant pembrolizumab, currently showing no evidence of recurrence. This case underscores the potential benefits of neoadjuvant chemoimmunotherapy for patients with ER+ErbB2- high-risk, basal-type breast cancer. The use of immunotherapy in patients with pregnancy-associated breast cancer remains to be further investigated.

Mucin-producing urothelial-type adenocarcinoma of the prostate with sarcomatoid features and novel molecular phenotype.

Introduction: Mucin-producing urothelial-type adenocarcinoma of the prostate is a rare tumor that may not elevate serum prostate-specific antigen, creating significant diagnostic and monitoring challenges. We evaluate our case in detail and review prior studies to demonstrate that the pathologic and molecular features of this tumor are distinct from conventional prostate adenocarcinoma. Case presentation: Our patient had a remote history of radiation-treated conventional prostate adenocarcinoma and presented many years later with an abscess-like prostate mass leading to urinary obstruction and hematuria. Biopsy revealed mucin-producing urothelial-type adenocarcinoma of the prostate with concurrent sarcomatoid features. Molecular studies showed a unique phenotype involving alterations in the KRAS, PTEN, RAD21, and TP53 genes. Conclusions: To our knowledge, this is the first report that describes sarcomatoid features and molecular mutations in mucin-producing urothelial-type adenocarcinoma of the prostate.

Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer: pathological implications in diagnosis.

PURPOSE: Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. MATERIAL AND METHODS: Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. RESULTS: MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p≤0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). CONCLUSION: The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma.

Upper urinary tract carcinoma in Lynch syndrome cases.

PURPOSE: Patients with Lynch syndrome are much more likely to have generally rare upper urinary tract urothelial carcinoma but not bladder urothelial carcinoma. While the risk has been quantified, to our knowledge there is no description of how this population of patients with Lynch syndrome and upper urinary tract cancer differs from the general population with upper urinary tract cancer. MATERIALS AND METHODS: We obtained retrospective data on a cohort of patients with Lynch syndrome from the Hereditary Cancer Center in Omaha, Nebraska and compared the data to those on a control general population from western Sweden. These data were supplemented by a new survey about exposure to known risk factors. RESULTS: Of the patients with Lynch syndrome 91% had mutations in MSH2 rather than in MSH1 and 79% showed upper tract urothelial carcinoma a mean of 15.85 years after prior Lynch syndrome-type cancer. Median age at diagnosis was 62 years vs 70 in the general population (p <0.0001). Only half of our patients had a significant smoking history and the male-to-female ratio was 0.95. Of patients with Lynch syndrome 51% had urothelial carcinoma in the ureter while it occurred in the renal pelvis in 65% of the general population (p = 0.0013). Similar numbers of high grade tumors were found in the Lynch syndrome and general populations (88% and 74%, respectively, p = 0.1108). CONCLUSIONS: Upper urinary tract tumors develop at a younger age and are more likely to be in the ureter with an almost equal gender ratio in patients with Lynch syndrome. It has high grade potential similar to that in the general population.

Cellient™ automated cell block versus traditional cell block preparation: a comparison of morphologic features and immunohistochemical staining.

Traditional cell block (TCB) sections serve as an important diagnostic adjunct to cytologic smears but are also used today as a reliable preparation for immunohistochemical (IHC) studies. There are many ways to prepare a cell block and the methods continue to be revised. In this study, we compare the TCB with the Cellient™ automated cell block system. Thirty-five cell blocks were obtained from 16 benign and 19 malignant nongynecologic cytology specimens at a large university teaching hospital and prepared according to TCB and Cellient protocols. Cell block sections from both methods were compared for possible differences in various morphologic features and immunohistochemical staining patterns. In the 16 benign cases, no significant morphologic differences were found between the TCB and Cellient cell block sections. For the 19 malignant cases, some noticeable differences in the nuclear chromatin and cellularity were identified, although statistical significance was not attained. Immunohistochemical or special stains were performed on 89% of the malignant cases (17/19). Inadequate cellularity precluded full evaluation in 23% of Cellient cell block IHC preparations (4/17). Of the malignant cases with adequate cellularity (13/17), the immunohistochemical staining patterns from the different methods were identical in 53% of cases. The traditional and Cellient cell block sections showed similar morphologic and immunohistochemical staining patterns. The only significant difference between the two methods concerned the lower overall cell block cellularity identified during immunohistochemical staining in the Cellient cell block sections.

Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a patient with lynch syndrome.

Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.

ThinPrep Pap test of endocervical adenocarcinoma with lymph node metastasis: report of a case in a 17-year-old woman.

Endocervical adenocarcinoma is an uncommon malignancy that is composed of multiple subtypes and accounts for approximately 15% of all cervical cancers. In this article, we describe the cytomorphology and differential diagnosis of an AJCC clinical stage IIIb, FIGO IB2 endocervical adenocarcinoma in a 17-year-old woman in a ThinPrep Pap test.The patient was a 17-year-old G0P0 white woman with no significant past medical history and no prior history of cervical dysplasia. She presented to her physician with a putrid vaginal discharge. A sample was sent to cytology that was interpreted as atypical endocervical cells, favor neoplasia. A subsequent cervical biopsy was diagnosed as endocervical adenocarcinoma with villoglandular features and ultimately, a hysterectomy with lymph node dissection was performed. The final diagnosis was endocervical adenocarcinoma with metastasis to three pelvic lymph nodes.The cytomorphology of endocervical adenocarcinoma on ThinPrep Pap test is similar to that described for conventionally-processed Pap smears. This difficult diagnosis should be considered on a ThinPrep Pap test, regardless of age when the characteristic cytomorphology is observed. On a cytology sample, it is advisable to state atypical endocervical cells, adenocarcinoma in situ, or endocervical adenocarcinoma without providing a specific subtype even if there is a predominance of features for a particular subtype.

Soft tissue tumors of the prostate: a review.

Prostate cancer is a leading cause of cancer-related death in adult men. Some prostates that are suspected to be involved by prostatic adenocarcinoma or nodular prostatic hyperplasia through clinical examination and imaging studies proves on histologic examination to be a soft tissue tumor. This paper outlines the most common soft tissue tumors of the prostate and categorizes them into benign, malignant or miscellaneous. Pathologists must be aware that most, if not all, soft tissue tumors of the body may also be found in the prostate. Diagnostic immunohistochemistry is an important adjunct to histopathology for proper diagnosis and tumor subclassification.

Seat belt use by police: should they click it?

BACKGROUND: Motor vehicle crashes are a leading cause of mortality in the United States, although seat belts significantly reduce the risk of death. Police officers do not always wear a seat belt. A retrospective study was conducted on all crashes that involved marked police vehicles in the United States and included a death in any of the involved vehicles. METHODS: For the years 1997 through 2001, crash data were collected and analyzed from the Fatality Analysis Reporting System that included an isolated or multiple vehicle crash with a marked police vehicle and a resulting death in any of the involved vehicles. Motorcycle, aircraft, and undercover police crashes were excluded from this study. Only the occupants of the police vehicle involved in the crash were included in the study. In addition, crashes involving police vehicles where the status of seat belt use by the occupants of the police vehicle was unknown were also excluded. RESULTS: When the crashes occurred, 59.9% of the officers were responding to nonemergency calls, 79.8% of the occupants were wearing their seat belts, and 79.5% survived. Of the 104 occupants that were not belted, 42 (40.4%) died in the crash, compared with 64 (15.5%) of the 412 belted occupants (risk ratio, 2.6; odds ratio, 3.7). CONCLUSION: The risk of death was 2.6 times higher for unbelted occupants of police vehicles than for belted occupants in our study population. In addition, seat belt use was not statistically related to emergency versus nonemergency calls.