Diagnostic Pathology最新文献

Background: Brain metastasis from prostate adenocarcinoma (PCa) is rare, often leading to death within a year. Its infrequent occurrence and atypical histopathologic features contribute to lower consideration in the differential diagnosis of tumor brain metastasis. This study aims to assess the clinical characteristics and distinctive histopathologic features of metastatic PCa in the brain for timely and enhanced diagnostic accuracy.

Design: A retrospective search spanning 20 years (2003-2022) was conducted on our archives and identified 21 cases diagnosed as "metastatic prostate adenocarcinoma (mPCa)" in brain biopsies and resections. All existing slides were thoroughly reviewed to evaluate the histopathology of the mPCa.

Result: The mean age at presentation for brain metastasis was 70 years. Of 21 cases, 5 were dural-based lesions, 16 were true intraparenchymal metastases, including 2 sellar/suprasellar masses, 3 frontal, 3 temporal, 3 occipital, 1 cerebellum, and 4 involving multiple brain lobes. The average interval between initial diagnosis and brain metastasis was 90.75 months. Notably, brain metastasis was the initial presentation for one patient, while another patient, initially diagnosed with prognostic grade group (GG) 2 PCa in 1/12 cores, presented with isolated brain metastasis two years later. Architecturally, tumor cells were arranged in sheets or nests in most cases; however, four cases showed histologic cribriform patterns, and five displayed papillary architecture. Cytohistology varied from uniform monomorphic to highly pleomorphic cells with prominent nucleoli (8/19) and high mitotic activity. Interestingly, 1 case showed small round blue cell morphology, another had focal areas of rhabdoid and spindle cell differentiation, and 6 had cytoplasmic clearing. Almost half of the cases (47%) showed necrosis.

Conclusion: mPCa to the brain can present with variable histomorphology. Therefore, consideration of mPCa in the differential diagnosis of metastatic brain lesions, even with non-suggestive imaging, is imperative in male patients with or without a history of primary disease. Accurate and prompt diagnosis is crucial, given the recent advancements in treatment that have improved survival rates.

Background: This study aims to analyze potential differences in clinicopathology, efficacy of neoadjuvant therapy (NAT), and clinical outcome among HER2-null, HER2-ultralow and HER2-low breast cancers.

Methods: Consecutive cases of HER2-negative breast cancer that received NAT were included. They were classified as HER2-null (no staining), HER2-ultralow (incomplete faint staining in ≤ 10% of tumour cells) and HER2-low (HER2-1 + or HER2-2+, in situ hybridisation negative). Subgroup analysis was performed based on the HER2 expression level.

Results: Out of 302 patients, 215 (71.19%) were HER2-low, 59 (19.54%) were HER2-ultralow, and 28 (9.27%) were HER2-null. In comparison to the HER2-ultralow group, the HER2-low group exhibited higher expression frequencies of ER (p < 0.001), PR (p < 0.001), and AR (p = 0.004), along with a greater prevalence of the luminal subtype (p < 0.001). The HER2-ultralow group also demonstrated a higher prevalence of lymph node metastasis compared to the HER2-null group (p = 0.026). Varied rates of pathologic complete response (pCR) were observed among the three subgroups: HER2-null, HER2-ultralow, and HER2-low, with rates of 35.71%, 22.03%, and 12.56%, respectively. Only the HER2-low subgroup exhibited a significant difference compared to HER2-null (p = 0.001). Despite variations in pCR rates, the three subgroups exhibited comparable disease-free survival (DFS) (p = 0.571). Importantly, we found HER2-low patients with better treatment response (RCB-0/I) exhibited significantly better DFS than those with significant residual disease (RCB-II/III) (P = 0.036). The overall rate of HER2 immunohistochemical score discordance was 45.24%, mostly driven by the conversion between HER2-0 and HER2-low phenotype. Notably, 32.19% of cases initially classified as HER2-0 phenotype on baseline biopsy were later reclassified as HER2-low after neoadjuvant therapy, and it is noteworthy that 22 out of these cases (78.57%) originally had an HER2-ultralow status in the pretreatment biopsy sample.

Conclusions: Our results demonstrate the distinct clinicopathological features of HER2-low and HER2-ultralow breast tumors and confirm that RCB is an effective predictor of prognosis in HER2-low populations for the first time. Notably, our findings demonstrate high instability in both HER2-low and HER2-ultralow expression from the primary baseline biopsy to residual disease after NAT. Furthermore, this study is the first to investigate the clinicopathological feature and the effectiveness of NAT for HER2-ultralow breast cancer.

Background: With the advent of targeted therapies, the survival prognosis for metastatic tumors has extended, and it has become necessary to diagnose and consider treatment that takes into account Quality of Life for metastatic tumors of the eye. The reports of checking tumor marker in the aqueous humor for diagnosis of metastatic intraocular tumors are few. Here, we report a case of masquerade syndrome with secondary glaucoma in which a high carcinoembryonic antigen (CEA) level in the aqueous humor could assist diagnosis, and continuing targeted therapy and trabeculectomy were effective.

Case presentation: A 73-year-old man was referred to us for iritis and high intraocular pressure (IOP) with severe eye pain in the left eye. He had Stage IVB lung adenocarcinoma treated with a molecularly targeted drug, Osimertinib. His best corrected visual acuity was 0.15, and IOP was 52 mmHg in the left eye. Anterior chamber cells (+), numerous small nodules in the iris, and small masses in the inferior angle were observed. In the aqueous humor, the CEA level was higher than in the blood. Napsin A and Thyroid Transcription Factor-1 (TTF-1) positive cells showed in the resected tissue at iridectomy performed during trabeculectomy. The pathological diagnosis of metastatic iris tumor of the lung adenocarcinoma was made, and we injected bevacizumab intravitreally once and continued Osimertinib. His IOP lowered to 8-10 mmHg, and the iris masses disappeared. He lost vision by metastasis to the left optic nerve after termination of Osimertinib one and a half years later. The metastasis shrank after restarting the drug. He passed away from an exacerbation of his primary lung cancer two years and nine months after the first visit. Although he lost vision in his left eye, the metastatic tumor in his left eye and optic nerve had disappeared, and his quality of life was maintained without any pain in his eye.

Conclusions: Checking tumor markers in the aqueous humor can aid in diagnosis, and aggressive treatment of metastatic iris tumors must help maintain patients' Quality of Life.

Backrgound: Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma, frequently associated with clonal Merkel cell polyomavirus integration. MCC can pose significant diagnostic challenges due to its diverse clinical presentation and its broad histological differential diagnosis. Histologically, MCC presents as a small-round-blue cell neoplasm, where the differential diagnosis includes basal cell carcinoma, melanoma, hematologic malignancies, round cell sarcoma and metastatic small cell carcinoma of any site. We here report strong aberrant immunoreactivity for BCOR in MCC, a marker commonly used to identify round cell sarcomas and other neoplasms with BCOR alterations.

Methods: Based on strong BCOR expression in three index cases of MCC, clinically mistaken as sarcoma, a retrospective analysis of three patient cohorts, comprising 31 MCC, 19 small cell lung carcinoma (SCLC) and 5 cases of neoplasms with molecularly confirmed BCOR alteration was conducted. Immunohistochemical staining intensity and localization for BCOR was semi-quantitatively analyzed.

Results: Three cases, clinically and radiologically mimicking a sarcoma were analyzed in our soft tissue and bone pathology service. Histologically, the cases showed sheets of a small round blue cell neoplasm. A broad panel of immunohistochemistry was used for lineage classification. Positivity for synaptophysin, CK20 and Merkel cell polyoma virus large T-antigen lead to the diagnosis of a MCC. Interestingly, all cases showed strong positive nuclear staining for BCOR, which was included for the initial work-up with the clinical differential of a round cell sarcoma. We analyzed a larger retrospective MCC cohort and found aberrant weak to strong BCOR positivity (nuclear and/or cytoplasmic) in up to 90% of the cases. As a positive control, we compared the expression to a small group of BCOR-altered neoplasms. Furthermore, we investigated a cohort of SCLC as another neuroendocrine neoplasm and found in all cases a diffuse moderate to strong BCOR positivity.

Conclusions: This study demonstrates that neuroendocrine neoplasms, such as MCC and SCLC can express strong aberrant BCOR. This might represent a diagnostic challenge or pitfall, in particular when MCC is clinically mistaken as a soft tissue or a bone sarcoma.

Background: Distinguishing reactive atypia from dysplasia in cholecystectomy specimens can be histologically challenging. The aim of this study was to evaluate the utility of IMP3, p53, and S100P immunostains in differentiating reactive atypia from dysplasia in cholecystectomies.

Methods: Fifty-four cholecystectomies were reviewed and characterized into 5 groups: 2 normal, 29 reactive atypia, 16 low-grade dysplasia, 2 high-grade dysplasia, and 5 adenocarcinoma. IMP3, p53, and S100P immunostains were performed and evaluated. IMP3 (nuclear) and S100P (nuclear or nuclear/cytoplasmic) were categorized into negative or positive expression, and p53 was categorized into wild-type and aberrant/mutant expression. Chi-square test was used for statistical analysis.

Results: The patients were mostly middle-aged women (mean 44, range 19-87 years, 81% female), with predominantly Hispanic White ethnicity (80%). The majority of the normal and reactive atypia cases showed negative IMP3 (100% and 75.9%, respectively) and wild-type p53 (100% and 89.7%, respectively) staining. Over half (56.3%) of the low-grade dysplasia and all the high-grade dysplasia cases showed IMP3 positivity. Aberrant p53 staining pattern was seen in half of both low and high-grade dysplasia cases. Adenocarcinoma showed IMP3 positivity in 80% and p53 aberrancy in all cases. S100P showed no statistical significance among the diagnostic categories. Significant differences in staining patterns were found between reactive atypia vs. low-grade dysplasia, and reactive atypia vs. low-grade + high-grade dysplasia using a combination of IMP3 and p53 stains (all p < 0.05).

Conclusions: In challenging cholecystectomies, IMP3 positivity or aberrant p53 expression may serve as a useful adjunct to support a diagnosis of dysplasia over reactive atypia.