Identifying erroneously used terms for vascular anomalies: A review of the English literature.

Background: The classification of vascular anomalies includes terms of nomenclature that are not based on histogenesis resulting in confusion among health professionals of different specialties. Ongoing efforts to classify them properly have taken place. This literature review aimed to identify erroneous nomenclature of vascular anomalies and to investigate their continued use over the past four years after the last International Society for the Study of Vascular Anomalies (ISSVA) update. Methods: Literature research was based on pertinent classifications (ISSVA, WHO) and books related to vascular anomalies and soft tissue pathology. After identifying twelve entities with confusing terminology, new research in the Pubmed database was conducted to verify their continued use in the last four years. Results: The literature review highlighted terms referring to vascular malformations as neoplasms. In addition, terms used as equivalents represent entirely different entities. On the other hand, different terms to characterize the same entity were also recorded. Furthermore, regardless of the last ISSVA update in 2018, terms that are only descriptive or do not correspond to vascular anomaly histogenesis are consistently used. Conclusion: Despite intensive efforts in the last decades for correct terminology and classification of vascular anomalies, modifications are still required. A common and broadly accepted scientific terminology should be applied, accurately representing histogenesis or pathogenesis, to obtain a common language among medical specialists, given that a multidisciplinary approach is crucial for managing vascular anomalies. HIPPOKRATIA 2022, 26 (4):126-130.

Giant malignant phyllodes tumor with distant metastases: a case report and review of the literature.

BACKGROUND: Phyllodes tumors (PTs) represent a rare type of breast tumor and are classified into benign, borderline, and malignant. Giant PTs, meaning those sized more than ten cm, are even rarer, most commonly malignant, and usually have a dismal prognosis due to the high metastatic potential. CASE REPORT: We report the case of a 55-year-old woman who underwent modified radical mastectomy and left axillary lymphadenectomy for a rapidly growing, giant, ulcerated mass of the left breast. Histopathologic examination revealed a malignant phyllodes tumor (MPT). Over one year after the initial surgery, the patient was found to have extensive thoracic and retroperitoneal metastases. CONCLUSION: Although giant PTs are uncommon, clinical suspicion should be high in rapidly growing breast mass patients. A comprehensive review of all metastatic giant MPT cases reported in the English literature emphasizes the lack of consensus regarding appropriate treatment. In the case of metastatic foci, pathologists need to be aware of the previous history to make a definitive diagnosis. Also, a comparative histopathologic study of the primary and metastatic tumors is sometimes necessary. HIPPOKRATIA 2022, 26 (1):41-45.

Monotherapy and combination therapy with acitretin for mycosis fungoides: results of a retrospective, multicentre study.

BACKGROUND: Retinoids have long been used in the treatment of cutaneous T-cell lymphomas. However, data on acitretin use for mycosis fungoides (MF) are very limited. OBJECTIVES: To evaluate treatment outcomes of acitretin in patients with MF attending three academic referral centres in different regions of Greece. METHODS: Data on effectiveness, safety and drug survival of acitretin as monotherapy or as adjuvant regimen were collected in a multicentre, register-based, retrospective study. RESULTS: Overall, 128 patients (64.8% male; mean age at MF diagnosis 59.7 years) were included. Folliculotropic MF was present in 24 (18.8%) cases. Most patients (n = 118; 92.2%) had early-stage disease (≤IIA) at acitretin initiation. In all, 28 (21.9%) patients received acitretin monotherapy, while 100 (78.1%) subjects on acitretin concomitantly received phototherapy (n = 65; 50.8%) or topical steroids (n = 27; 21.1%). Acitretin was given as a first-line agent in 73 (57%) cases. A 77.3% overall response rate was noted: 44.5% and 32.8% for complete and partial responses, respectively. Acitretin was more effective as first-line than as a subsequent agent (P = 0.008). A trend towards better response was observed in the combination arm compared to patients receiving acitretin alone (P = 0.056). Median time to best response was 6.9 months (IQR 4.4-9.4); median duration of response was 23.7 months (IQR 11.9-35.4). Overall, the mean length of all treatment patterns was 569 days (SD 718.8). Therapy was discontinued in 5 (3.9%) cases due to drug intolerance. Adverse effects were recorded in 62 (48.4%) cases with dyslipidaemia (n = 31; 24.2%), xerosis (n = 24; 18.6%) and hair loss (n = 10; 7.8%) being the most commonly recorded. CONCLUSIONS: Acitretin, either alone or as adjuvant, showed a stable long-term effectiveness in this cohort, especially when used in the first-line setting. This RAR-selective agonist may serve as an attractive option for treatment of MF and should be further evaluated.

The PROCLIPI international registry of early-stage mycosis fungoides identifies substantial diagnostic delay in most patients.

BACKGROUND: Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging. OBJECTIVES: To develop a prognostic index for MF. METHODS: Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. RESULTS: In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 12-90)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. CONCLUSIONS: This confirmed early-stage MF cohort is being followed-up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.

Management of peritoneal hydatid cysts: A fourty-year experience.

BACKGROUND: Hydatid disease is a global problem. We report our experience with such cases where the dominant cysts were located outside the liver and lungs. In particular, these cysts were found in the peritoneum which is an uncommon location. METHODS: Between 1967 and 2007 a total of 34 patients were operated for primary or secondary peritoneal cysts. Most of the patients were asymptomatic or had atypical symptoms. The diagnosis was based on the preoperative history, rupture of the cysts, serology, ultrasound (USS) and computer tomography (CT). Open surgery was the procedure of choice with conservative (18 cysts) and radical (25 cysts) methods. RESULTS: The outcome of surgery was good without postoperative mortality or severe morbidity and the recurrence rate was 23.5%. CONCLUSIONS: Conservative surgery can provide good results in symptomatic peritoneal cysts. Radical therapy is also ideal but only in properly selected cases. The management of this situation is difficult requiring sound operative experience preferably with a one-stage procedure after an appropriate preoperative preparation.

Vitamin D receptor and progesterone receptor protein and gene expression in papillary thyroid carcinomas: associations with histological features.

PURPOSE: Vitamin D receptor (VDR) and progesterone receptor (PR) expression has been described in papillary thyroid carcinoma (PTC) but data regarding association with tumor histological characteristics and localization of the protein expression are scarce. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded specimens from 45 patients with PTC (cases) were retrieved and tumor histological data were recorded. We analyzed gene and protein expression of VDR and PR and gene expression of vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzymes in follicular cancer cells and the adjacent non-neoplastic thyroid tissue (NNTT). RESULTS: VDR mRNA and protein expression was higher in PTC compared with NNTT (p < 0.05). The protein was globally localized in the cytoplasm and cell membranes of the neoplastic cells in all cases, with differences in intensity. Cytoplasmic positivity was stronger in the majority of cases. Membranous positivity was also evident in cases, whereas in NNTT was generally weak and in a low percentage of the cells. Expression of CYP 24A1, but not CYP27B1, was increased in approximately all PTC specimens and was associated with lymph node metastasis and extrathyroidal extension. PR mRNA was increased in 34% and protein expression was present in 57% of cases, and none of NNTT. PR, but not VDR, mRNA expression was significantly associated with the tumor size (r = 0.645, p = 0.007). CONCLUSIONS: We provide evidence for the expression pattern of VDR, PR and CYP24A1 in the progression of PTC. Rapid anti-tumor responses of vitamin D in PTC may be blocked due to inactivation of local vitamin D metabolism.

Thyroid transcription factor-1 expression in invasive and non-invasive urothelial carcinomas.

BACKGROUND: Thyroid transcription factor-1 (TTF-1) has been considered a sensitive marker for thyroid and lung tumors. Recent data have shown that a wide range of neoplasms may express TTF-1. CASE SERIES: We performed an immunohistochemical study in a case series of 42 urothelial carcinomas (UCs) on tissue microarrays sections, in order to investigate how often UCs express the TTF-1 protein and the diagnostic utility of this marker. In addition, we sought to determine by immunohistochemistry if there is an association between TTF-1 expression and the expression of specific basal-like or luminal markers. Five out of the 42 cases (11.9 %) were positive for TTF-1. Three positive tumors concerned non-invasive papillary UCs. There was no association between TTF-1 expression and tumor grade (χ2, p =0.419), stage (χ2, p =0.550) or cytokeratin 5/6 (χ2, p =0.330), cytokeratin 20 (χ2, p =0.995) and estrogen receptors expression (χ2, p =0.268). CONCLUSIONS: UCs may show TTF-1 expression and pathologists should be aware of this phenomenon in order to avoid misdiagnosis, notably in metastatic disease. HIPPOKRATIA 2017, 21(3): 154-157.

Prognostic indicators for mycosis fungoides in a Greek population.

BACKGROUND: Mycosis fungoides (MF) is an indolent cutaneous lymphoma with excellent prognosis at early stages and much poorer outcome during disease progression. Old age, male sex and folliculotropism have been proposed as relevant prognostic factors; however, their exact effect remains debatable. OBJECTIVES: To evaluate MF prognostic indicators and survival rates in a Greek population. METHODS: Prognostic variables affecting survival rates were studied in 473 patients with MF diagnosed and treated by two academic referral centres in Greece. Kaplan-Meier estimates were used to determine survival rates and progression. The Cox proportional hazards regression model was used to assess prognostic factors. RESULTS: The mean age of diagnosis was 61·7 years (SD 16·33). Five-year disease-specific survival was 96% in patients with stage IA disease and 52% in patients with stage IIB disease. Univariate analysis certified that large-cell transformation, clonal rearrangements of the TCR gene, severe pruritus and presence of plaques were the most important prognostic factors. Folliculotropism altered disease progression only in patients with early-stage disease. The application of the Cutaneous Lymphoma International Prognostic Index (CLIPI) on our late-stage group failed to provide reliable evidence. The current Cutaneous Lymphoma International Consortium (CLIC) prognostic index can efficiently distinguish a low-risk from a high-risk group of patients. Tumour-Node-Metastasis-Blood (TNMB) staging was the most important prognostic factor for survival rates in multivariate analysis. CONCLUSIONS: In our study we validated the current prognostic indicators for MF in a Greek population and identified new potential prognostic factors for survival outcome. Our findings contribute to the ongoing investigation of prognostic indicators of MF, further validation of which is highly needed through prospective studies and among different populations.

Neuroendocrine carcinoma in adenoma of the sigmoid.

BACKGROUND: Neuroendocrine cell tumor in adenoma of the sigmoid is a rare neoplasm coexistence and it is considered as a mixed glandular-neuroendocrine neoplasm. DESCRIPTION OF CASE: An 84-year-old woman underwent surgical removal of a tumor located in the sigmoid, diagnosed as adenocarcinoma on a previous biopsy. On gross examination, apart from the ulcerated tumor, a polyp measuring 2 cm was observed, which histologically corresponded to a villotubular adenoma. In two sites of the adenoma, solid nests of smaller cells were observed, having small amount of cytoplasm, round nuclei with finely stippled chromatin. Mitoses were abundant. These cells were located in the lamina propria and muscularis mucosa, without disturbing the polyp architecture, and showed immunophenotypic characteristics of neuroendocrine carcinoma (NEC). The histologic findings set the diagnosis of mixed adenoma and NEC. The patient remains free of recurrence or metastasis by NEC, after two years of follow up. CONCLUSION: The recognition of NEC in an adenoma will help to avoid potential diagnostic pitfalls. Mixed adenoma and NEC is rare, with uncertain biological behavior. This case reinforces the view that NECs without infiltration of submucosa may have a better prognosis.

Primary prostatic lymphoma with components of both diffuse large B-cell lymphoma (DLBCL) and MALT lymphoma.

Although lymphomas involving the prostate gland are rare, they should always be considered in the differential diagnosis. We report a case of primary prostatic NHL in a 70-year-old man presented with hematuria and urinary obstructive symptoms. Routine laboratory tests were within normal limits and prostate-specific antigen (PSA) was 0,01 ng/ml. The patient underwent radical prostatectomy. Histologically, two different coexisting patterns of non-Hodgkin lymphoma, infiltrating the prostatic tissue, were identified. The diagnosis of diffuse large B-cell lymphoma (DLBCL) presenting with an associated low-grade lymphoma of MALT-type was confirmed by immunohistochemistry. The patient received chemotherapy without any complication and has been followed-up for 2 years since surgical resection with no recurrence. The clinicopathologic characteristics of prostatic lymphomas are discussed, while reviewing the current English-language literature.

EGFR expression and activation are common in HER2 positive and triple-negative breast tumours.

EGFR has been associated with unfavourable prognosis in patients with triple-negative breast carcinomas, although little is known about EGFR activation in these tumours. In a series of breast carcinomas (archived formalin fixed tumours, n=100), we investigated EGFR phosphorylation status at Tyr992 (pEGFR-Y992) and Tyr1068 (pEGFR-Y1068) by immunohistochemistry, along with EGFR protein expression (extracellular domain), gene amplification status (fluorescent in situ hybridization) and conventional clinicopathologic parameters. EGFR protein was present in 21.9%, while phosphorylation at Y1068 and Y992 was observed in 27.8% and 50.5% of tumours, respectively. None of the tumours showed EGFR gene amplification, whereas 21.1% exhibited chromosome 7 polysomy. The above EGFR parameters were usually not simultaneously detected and were not associated with each other. High grade (p=0.003), lymph node positive (p=0.045), estrogen receptor (ER) negative (p<0.001) tumours often expressed EGFR protein. EGFR-Y992 and Y1068 phosphorylation was inversely associated with ER presence (p=0.023 and p=0.029, respectively) but positively with HER2 expression status (p<0.001 and p=0.002, respectively). The global positivity for any EGFR parameter did not significantly differ between triple-negative and HER2 positive tumours. In conclusion, EGFR phosphorylation is commonly encountered in breast carcinomas, although unrelated to EGFR protein presence and gene amplification. EGFR may appear activated even in cases where the extracellular domain of this protein is not observed with immunohistochemistry. These findings may be useful for further studies aiming at the assessment of EGFR parameters on this type of material.

Smooth muscle cell differentiation in the processus vaginalis of children with hernia or hydrocele.

PURPOSE: Incomplete obliteration of the processus vaginalis (PV) in children with inguinal hernia or hydrocele has recently been proposed to relate to smooth muscle cell (SMC) persistence. The aim of this study was to evaluate the diversity and differentiation of smooth muscle phenotypes in sacs associated with inguinal hernia and hydrocele through the expression of alpha-smooth muscle actin (SMA), h-caldesmon, desmin, and vimentin. METHODS: Sacs associated with male hernia (n = 22), female hernia (n = 8), and hydrocele (n = 10) were immunohistochemically evaluated using monoclonal antibodies against SMA, h-caldesmon, desmin, and vimentin. Peritoneal samples (male, 4; female, 3) and obliterated PV (male, 3) obtained from age-matched patients served as controls. Expressions according to the groups were compared through chi-squared test, and P values less than 0.05 were considered to be statistically significant. RESULTS: Immunohistochemistry did not shown the presence of SMCs in control samples. The expression of SMA, desmin, and h-caldesmon did not differ among sacs obtained from patients with inguinal hernia and hydrocele. However, strong expression of vimentin in SMCs within sacs obtained from patients with hydrocele in comparison with sacs from male patients with inguinal hernia were observed. CONCLUSIONS: Our results indicate that sacs from patients with inguinal hernias and especially from male inguinal hernias have fully differentiated SMCs. On the other hand SMCs in sacs obtained from boys with hydrocele are in an intermediate state of differentiation-dedifferentiation. This phenotypic modulation may represent attempted apoptosis of SMCs, since sacs more sensitive to apoptosis appeared to have more dedifferentiated SMCs. It also probably depicts the differing influence of sympathetic and parasympathetic tonuses during the descent of the testis and the obliteration of PV.