Immunohistochemical detection of EGFRvIII in glioblastoma - Anti-EGFRvIII antibody validation for diagnostic and CAR-T purposes.

The emergence of therapies such as CAR-T has created a need for reliable, validated methods for detecting EGFRvIII in patient tumor cells. Particularly so since previous studies have already suggested that some anti-EGFRvIII antibodies may be non-specific. The present paper evaluates the use of the L8A4 antibody in the immunohistochemical (IHC) and immunocytochemical (ICC) detection of EGFRvIII in 30 glioblastoma specimens, and compares it with other methods such as RT-PCR, MLPA, and FISH. The results indicate that Real-time PCR appears to be a very specific and sensitive method of EGFRvIII detection. ICC analysis with L8A4 also appears specific but requires cell culture. IHC analyses of EGFRvIII returned a number of false positives when using L8A4. Due to the growing need for an effective diagnostic tool before starting immunotherapy methods, such as the CAR-T anti-EGFRvIII or SynNotch CAR-T recognizing EGFRvIII, it is necessary to identify a more reliable and simple method of EGFRvIII detection or improve the specificity of the anti-EGFRvIII antibody, until then, immunocytochemistry may temporarily replace immunohistochemistry.

Primary pulmonary Hodgkin's lymphoma mimicking granulomatosis with polyangiitis - a case report of diagnostic and therapeutic dilemmas.

Primary pulmonary Hodgkin's lymphoma (PPHL) is a rare subtype of lymphoma that comprises a small percentage of primary pulmonary lymphomas. Due to its rarity and nonspecific symptoms, PPHL often presents diagnostic challenges. This case report presents a unique case of PPHL mimicking granulomatosis with polyangiitis, emphasizing the difficulties encountered during the diagnostic process. A 53-year-old female presented with vague symptoms including weakness, oedema, dry cough, and nasal cavity ulceration. Laboratory investigations revealed elevated C-reactive protein levels, a white blood cell count with neutrophilia, and lymphopaenia. Initial treatment with oral corticosteroids for suspected polyangiitis yielded no response. The patient subsequently developed a low-grade fever and pruritic erythematous rash. Diagnostic procedures, including bronchial brush biopsy, bronchial washing, mediastinal lymph node biopsy, nasal cavity ulceration biopsy, and initial lung biopsy, were inconclusive and resulted in exclusion of granulomatosis with polyangiitis. A subsequent computed tomography scan indicated disease progression in the left lung. A lung biopsy revealed fibrotic tissue with nodules containing Hodgkin- Reed-Sternberg cells, leading to the final diagnosis of classic Hodgkin lymphoma, nodular sclerosis subtype. Positron emission tomography scan findings confirmed PPHL. The patient received multiple chemotherapeutic regimens, with brentuximab vedotin demonstrating efficacy as the sole effective treatment. This exceptional case of PPHL underscores the extensive diagnostic and therapeutic workup involving a multidisciplinary team of clinicians, radiologists, and pathologists. Increased awareness of PPHL and its distinctive features will aid in the diagnosis of similar cases in the future, benefitting both clinicians and pathologists.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in Poland: analysis of patient series and practical guidelines for breast surgeons.

Introduction: Although breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is infrequent, with less than 1000 noted cases worldwide, patients consenting for breast implant surgery should be aware of its risk. We describe the first Polish multicenter case-series data on BIA-ALCL patients and present diagnostic and treatment recommendation for breast surgeons. Material and methods: In cooperation with the Polish Society of Surgical Oncology and Polish Lymphoma Research Group, we collected BIA-ALCL cases in Poland. Results: We retrospectively reviewed clinical data of seven BIA-ALCL patients, diagnosed between July 2013 and November 2019. The median time from implant placement to the first BIA-ALCL symptoms was 65 months (range: 33-96 months). All the patients were exposed to textured implants at presentation. Capsulectomy with implant removal was performed in all the patients with immediate reimplantation in 2 cases. In a median follow-up of 19 months (range 5-81 months), there was no recurrence and all the patients stayed alive. Between 2013 and 2019, the incidence of BIA-ALCL in Polish female population age 30 and above ranged from 0 to 0.021/100 000/year. Conclusions: BIA-ALCL is scarce in the Polish population. In a short-term follow-up, patients' prognosis remains excellent. Due to the withdrawal of roughly textured implants from the market and the exclusion of likely the most potent etiologic factor, it might be expected that the incidence of BIA-ALCL will become even rarer.

Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients.

BACKGROUND: Primary glioblastoma is characterized by an extremely poor prognosis. The promoter methylation of GATA4 leads to the loss of its expression in many cancer types. The formation of high-grade astrocytomas can be promoted by the concurrent loss of TP53 and GATA4 in normal human astrocytes. Nevertheless, the impact of GATA4 alterations with linkage to TP53 changes in gliomagenesis is poorly understood. This study aimed to evaluate GATA4 protein expression, GATA4 promoter methylation, p53 expression, TP53 promoter methylation, and mutation status in patients with primary glioblastoma and to assess the possible prognostic impact of these alterations on overall survival. MATERIALS AND METHODS: Thirty-one patients with primary glioblastoma were included. GATA4 and p53 expressions were determined immunohistochemically, and GATA4 and TP53 promoter methylations were analyzed via methylation-specific PCR. TP53 mutations were investigated via Sanger sequencing. RESULTS: The prognostic value of GATA4 depends on p53 expression. Patients without GATA4 protein expression were more frequently negative for TP53 mutations and had better prognoses than the GATA4 positive patients. In patients positive for GATA4 protein expression, p53 expression was associated with the worst outcome. However, in patients positive for p53 expression, the loss of GATA4 protein expression seemed to be associated with improved prognosis. GATA4 promoter methylation was not associated with a lack of GATA4 protein expression. CONCLUSIONS: Our data indicate that there is a possibility that GATA4 could function as a prognostic factor in glioblastoma patients, but in connection with p53 expression. A lack of GATA4 expression is not dependent on GATA4 promoter methylation. GATA4 alone has no influence on survival time in glioblastoma patients.

Prognostic value of XIAP and survivin expression in locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.

Introduction: Neoadjuvant treatment in locally advanced breast cancer (LABC) is intended to decrease the cancer mass, increase the likelihood of radical resection and improve survival. Resistance to chemotherapy may depend on cellular expression of anti-apoptotic proteins. XIAP and survivin are the most potent inhibitors of apoptosis (IAP), but their role in drug-induced cancer cell apoptosis remains unclear. This study was designed to evaluate the impact of pre-treatment expression of XIAP and survivin on pathological complete response and survival in LABC patients. Material and methods: The study included 60 LABC patients treated with anthracycline-based chemotherapy. XIAP and survivin expression was assessed immunohistochemically in pre-treatment core biopsy specimens. Results: Pathological complete response was achieved in 33% of the LABC patients. Low/intermediate expression of both XIAP and survivin was significantly associated with pathological complete response (p ≤ 0.04 and p < 0.001, respectively) and positively correlated with disease-free survival (p = 0.017 and p < 0.001) and overall survival (p = 0.052 and p < 0.001). The area under receiver operating characteristics curves (AUC) revealed predictive value of survivin expression for relapse and death in breast cancer patients (AUC = 0.63, p = 0.001 and AUC = 0.8, p < 0.001, respectively). Conclusions: Our findings suggest that downregulation of XIAP and survivin in LABC patients might predict better treatment outcomes after anthracycline-based chemotherapy. This, in turn, may indicate XIAP and survivin proteins as potential targets for innovative anticancer therapies.

An unusual non­metastatic, mismatch repair­deficient primary gastric squamous cell carcinoma presenting as a large, exophytic, bleeding tumor: A case report.

Primary gastric squamous cell carcinoma (GSCC) is an extremely rare malignancy with a poor prognosis. Despite the improved knowledge regarding its pathogenesis and biology, the treatment options remain limited. The present study reported on the unique case of a mismatch repair-deficient (dMMR) primary GSCC in a 79-year-old woman reporting fatigue and symptoms of upper gastrointestinal tract bleeding. Physical examination revealed abdominal pain at palpation. Gastroscopy revealed a large, exophytic, bleeding tumor. Medical imaging confirmed a mushroom-like polyp in the lumen of the stomach, with no signs of disease spread. Total gastrectomy and D2 lymphadenectomy were performed. Pathological examination of the post-operational material confirmed a well-differentiated SCC invading the mucosa, submucosa and muscle layer. There were no signs of dissemination observed in any of the 32 excised lymph nodes. Notably, according to the last follow-up, the patient remains well, supporting the 5-year GSCC survival rate statistics. To the best of our knowledge, this is the first such GSCC case reported in the Surgical Oncology Outpatient Clinic (Copernicus Memorial Hospital, Lodz, Poland) and these findings add to the limited data on GSCC. Although this is a very rare condition, it should always be considered during the process of diagnosis of gastric tumors.

Cardiac Involvement in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Cardiac involvement of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is recognized extremely rarely. In addition, most CLL/SLL patients with heart infiltration are asymptomatic. In this review, we present the results of a literature search for English language articles concerning CLL/SLL or Richter transformation with symptomatic cardiac involvement. In total, 18 well-described cases with CLL/SLL and heart infiltration were identified. Only three patients were not diagnosed with CLL/SLL before the cardiac manifestation. In other patients, cardiac CLL/SLL was diagnosed between 5 months and 20 years from CLL/SLL diagnosis. All patients in these series had a diagnosis of secondary cardiac CLL/SLL. In addition, we identified four reported cases with Richter transformation in the heart. The treatment of patients with CLL/SLL and cardiac infiltration is variable and depends on the previous history and clinical characteristics of heart infiltration. In addition, no recommendations exist on how to treat patients with CLL/SLL and cardiac involvement.

Urothelial carcinoma of the prostate with raised ß-hCG levels: a case report.

BACKGROUND: Trophoblastic differentiation in primary urothelial carcinoma of the prostate is extremely rare. An increased level of ß-subunit human chorionic gonadotropin in serum in urothelial carcinoma is detected in approximately 30% of cases. To our knowledge, increased concentration of ß-subunit human chorionic gonadotropin in serum in prostatic urothelial carcinoma has never been reported and its clinical significance is not evaluated yet. CASE REPORT: Here we present the case of a 67-year-old European patient who was admitted to the hospital with hematuria, dysuria, and enlarged painful testis. Ultrasonographic examination of the testis did not reveal any focal lesion. Magnetic resonance imaging of the pelvis showed a tumor of 62 mm diameter mainly located in the posterior part of the prostatic gland. A pathological examination from cystoscopy biopsy allowed us to set the diagnosis of high-grade invasive urothelial carcinoma with trophoblastic differentiation. The patient received neoadjuvant treatment. Nonetheless, after a short period of disease stabilization, he developed progression and brain metastasis. He died 9 months after diagnosis. During the disease course, his ß-human chorionic gonadotropin level was measured repeatedly and analyzed in relation to disease progression. The level of serum ß-human chorionic gonadotropin corresponded with the therapy response; it was at its lowest during stabilization and the highest in the metastatic stage. CONCLUSION: Our case study provides the first report of urothelial cancer of the prostate, with a concomitant increase of ß-subunit human chorionic gonadotropin level with testis enlargement. Besides its rarity, it constitutes an interesting observation of increasing ß-subunit human chorionic gonadotropin concentration with concomitant disease progression.

Clinical significance of CD34, podoplanin and Ki-67 expression in patients with locally advanced squamous cell cervical carcinoma.

The aim of the study was to assess immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of patients with cervical squamous cell carcinoma (SCC) staged IIB and IIIB, a relationship with selected clinical and histological parameters and its prognostic significance. This prospective study included 52 patients. Microvessel density (MVD) by CD34, lymphatic vessel density (LVD) by podoplanin and the Ki-67 index in specimens from paraffin blocks with cervical SCC tissues were examined. The relationship between these data and selected clinical and histological parameters was analysed. Positive correlation of MVD and the Ki-67 index was observed. No correlation was observed for MVD, LVD and the Ki-67 index in the tumour with staging, grading, length of treatment and squamous cell carcinoma antigen (SCC-Ag) concentration before and after treatment. The expression of MVD, LVD and the Ki-67 index in cervical SCC did not contribute to the risk of relapse and cancer-related death. No relationship was found for MVD, LVD and the Ki-67 index in cervical tumour of patients with locally advanced cervical SCC with staging, grading and serum SCC-Ag level. MVD, LVD and the Ki-67 index in the tumour did not contribute to the risk of relapse or cervical SCC-related death.Impact StatementWhat is already known on this subject? In many patients, invasive cervical squamous cell carcinoma (SCC) is diagnosed in a locally advanced stage, when the prognosis depends on many well-known factors connected with tumour biology, staging and general condition of the patient. Despite numerous studies, the value of immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of these patients is still not well defined.What do the results of this study add? In our prospective study, no relationship for microvessel density (MVD), lymphatic vessel density (LVD) and the Ki-67 index in cervical tumour of patients with locally advanced cervical SCC with staging, grading and serum squamous cell carcinoma antigen (SCC-Ag) level was found. Additionally, MVD, LVD and the Ki-67 index in the tumour did not contribute to the risk of relapse or cervical SCC-related death.What are the implications of these findings for clinical practice and/or further research? Our study underlines the limited value of immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of patients with locally advanced cervical SCC. Further research should be focussed on identifying and validating novel prognostic and predictive factors.

Liver metastasis or a pseudocyst? A rare presentation of leiomyosarcoma's metastasis in the liver.

Gastrointestinal neoplasms most commonly metastasize to the liver, where they are typically found as solid and hypervascular lesions. Here, we describe a case of a 44-year-old man with a leiomyosarcoma of the rectum, who at the time of diagnosis presented with a small (5 mm in diameter) cyst-like lesion in the liver. Positron emission tomography demonstrated no increased metabolism in the area of the cyst, suggesting a benign character of the lesion. However, after 3 years, CT scans revealed enlargement of the cyst, and local surgical excision was performed. The results of histopathological examination of the resected material were consistent with metastatic leiomyosarcoma. Subsequently, the patient developed lung metastases and died within 2 years. Our case describes a very rare presentation of leiomyosarcoma's metastasis that led to an ill-fated misdiagnosis and dismal disease outcome.

Skin changes in hairy cell leukemia.

Skin lesions have been reported in about 10-12% of hairy cell leukemia (HCL) patients. Most are etiologically related to autoimmune or infectious processes, although secondary cutaneous neoplasms and drug-induced lesions are also reported. However, leukemia cutis with the direct infiltration of the skin by leukemic cells is extremely rare in HCL patients. This paper reviews the epidemiology, pathogenesis, clinical symptoms, diagnosis, and approach to treating skin lesions in HCL. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skin lesions, leukemia cutis, adverse events, infectious, cutaneous, drug reactions, neutrophilic dermatoses, secondary neoplasms, and vasculitis was conducted via PubMed. Publications from January 1980 to September 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.

Broad phenotypic spectrum of germ line 7p12.1 microdeletions encompassing the IKZF1 gene includes predisposition to acute lymphoblastic leukemia.

Microdeletions of 7p12.1 encompassing the IKZF1 gene locus are rare, with few cases reported. The common phenotype includes intellectual disability, overgrowth, and facial dysmorphism accompanied, albeit rarely, by congenital anomalies. Haploinsufficiency of IKZF1 predisposes individuals to childhood acute lymphoblastic leukemia (ALL). In this study, we comprehensively analyzed the frequency of 7p12.1 deletions among 4581 Polish individuals who underwent chromosomal microarray testing for unexplained developmental delay, intellectual disability, and/or congenital anomalies. Two unrelated individuals (0.04%) with a de novo interstitial 7p12.1 microdeletion encompassing IKZF1 were identified. One developed ALL. Analysis of the incidence and the phenotype of constitutional 7p12.1 microdeletion, which based on the previously annotated patients data in public databases and literature reports, revealed 21 cases including five patients diagnosed with ALL.

Serous borderline tumor with distant mediastinal metastasis? An Exceptional presentation of ovarian tumor.

Borderline ovarian tumor is a non-invasive lesion with an excellent prognosis. Here we report a case of 48-year-old woman with distinctive clinical presentation of metastasis of ovarian adenocarcinoma, which was an microinvasive component of a serous borderline tumor. On initial diagnosis patient did not present any clinical manifestation of ovarian tumor. Histological examination of resected ovary showed typical features of the serous borderline tumor with one very diminutive focus of invasive serous adenocarcinoma 4mm in diameter. This exceptional case shows that borderline tumors of ovary with any features of invasion could present an aggressive course with distant metastases.

Publisher Correction: Classification of aggressive and classic mantle cell lymphomas using synchrotron Fourier Transform Infrared microspectroscopy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Bone lesions in hairy cell leukemia: Diagnosis and treatment.

Skeletal involvement is a rare complication of hairy cell leukemia (HCL) with an incidence of approximately 3%. Bone lesions are commonly lytic, and the most common sites of involvement are the femoral head and neck. Skeletal involvement is typically associated with high tumor burden and bone marrow infiltration. However, isolated cases of skeletal disease without splenomegaly or bone marrow involvement are occasionally reported. This review focuses on skeletal lesions in HCL, particularly the pathogenesis, clinical symptoms, diagnostic methods, and treatment approach. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skeletal symptoms, bone involvement was conducted via PubMed. Publications from January 1970 to May 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.

Adenoid cystic carcinoma of the breast - an uncommon malignancy with unpredictable clinical behaviour. A case series of three patients.

Adenoid cystic carcinoma (AdCC) is a common tumour of the minor salivary gland, rarely seen in other anatomical locations. In particular, AdCC of the breast accounts for < 0.1% of patients diagnosed with breast cancer. Here we report our institutional experience with three cases of breast AdCC diagnosed between 2009 and 2017. Mean age of women included in the report was 53 (range from 41 to 62). One case was of no special subtype, two were solid variants and one presented with a component of invasive ductal carcinoma. At diagnosis in all cases neither lymph node involvement nor distal metastases were detected. All patients underwent surgical resection of the tumour - mastectomy or lumpectomy, followed by either adjuvant radiotherapy and chemotherapy (one case), chemotherapy without radiotherapy (one case) or no treatment (one case). Two patients were reported to develop metastatic disease. No deaths were recorded. In contrast to other anatomical locations AdCC of the breast is regarded as a rare tumour with low malignant potential. However, as shown in our case series, it can present as an aggressive disease with distal metastases, which calls for deep awareness among both pathologists and clinicians involved in the process of diagnosis and therapy.