Proposal of Novel Binary Grading Systems for Cervical Squamous Cell Carcinoma.

We compared grading systems and examined associations with tumor stroma and survival in patients with cervical squamous cell carcinoma. Available tumor slides were collected from 10 international institutions. Broders tumor grade, Jesinghaus grade (informed by the pattern of tumor invasion), Silva pattern, and tumor stroma were retrospectively analyzed; associations with overall survival (OS), progression-free survival (PFS), and presence of lymph node metastases were examined. Binary grading systems incorporating tumor stromal changes into Broders and Jesinghaus grading systems were developed. Of 670 cases, 586 were reviewed for original Broders tumor grade, 587 for consensus Broders grade, 587 for Jesinghaus grade, 584 for Silva pattern, and 556 for tumor stroma. Reproducibility among grading systems was poor (κ = 0.365, original Broders/consensus Broders; κ = 0.215, consensus Broders/Jesinghaus). Median follow-up was 5.7 years (range, 0-27.8). PFS rates were 93%, 79%, and 71%, and OS rates were 98%, 86%, and 79% at 1, 5, and 10 years, respectively. On univariable analysis, original Broders ( P < 0.001), consensus Broders ( P < 0.034), and Jesinghaus ( P < 0.013) grades were significant for OS; original Broders grade was significant for PFS ( P = 0.038). Predictive accuracy for OS and PFS were 0.559 and 0.542 (original Broders), 0.542 and 0.525 (consensus Broders), 0.554 and 0.541 (Jesinghaus grade), and 0.512 and 0.515 (Silva pattern), respectively. Broders and Jesinghaus binary tumor grades were significant on univariable analysis for OS and PFS, and predictive value was improved. Jesinghaus tumor grade ( P < 0.001) and both binary systems (Broders, P = 0.007; Jesinghaus, P < 0.001) were associated with the presence of lymph node metastases. Histologic grade has poor reproducibility and limited predictive accuracy for squamous cell carcinoma. The proposed binary grading system offers improved predictive accuracy for survival and the presence of lymph none metastases.

Extensive versus focal lymphovascular invasion in squamous cell carcinoma of the cervix: A comprehensive international, multicenter, retrospective clinicopathologic study.

OBJECTIVE: We evaluated clinicopathologic parameters of patients with cervical squamous cell carcinoma (SCC) who were treated with initial surgical management and assessed their relation to survival outcomes. Specifically, we evaluated the relation between extent of lymphovascular invasion (LVI) and survival outcomes. METHODS: All available tumor slides from patients with initially surgically treated cervical SCC were collected from 10 institutions and retrospectively analyzed. Standard clinicopathological parameters, tumor stroma, and extent of LVI were assessed (focal: <5 spaces, extensive: ≥5 spaces). PFS and OS were evaluated using Kaplan-Meier methodology. Univariable and multivariable Cox proportional hazards models were created to determine prognostic survival-related risk factors. RESULTS: A total of 670 tumor samples were included in the analysis. Median age at diagnosis was 47 years (IQR: 38-60), 457 patients (72%) had a 2018 International Federation of Gynecology and Obstetrics (FIGO) stage I tumor, and 155 tumors (28%) were flat and/or ulcerated. There were 303 nonkeratinizing tumors (51%), 237 keratinizing tumors (40%), and 356 histologic grade 2 tumors (61%). Quantifiable LVI was present in 321 cases (51%; 23% focal and 33% extensive). On multivariable analysis for PFS, extensive and focal LVI had worse outcomes compared to negative LVI (HR: 2.38 [95% CI: 1.26-4.47] and HR: 1.54 [95% CI: 0.76-3.11], respectively; P = 0.02). The difference did not reach statistical significance for OS. CONCLUSION: Presence of LVI is a prognostic marker for patients with cervical SCC. Quantification (extensive vs. focal vs. negative) of LVI may be an important biomarker for oncologic outcome.

Cervical Adenosquamous Carcinoma: Detailed Analysis of Morphology, Immunohistochemical Profile, and Outcome in 59 Cases.

Although both the 2014 and 2020 World Health Organization (WHO) criteria require unequivocal glandular and squamous differentiation for a diagnosis of cervical adenosquamous carcinoma (ASC), in practice, ASC diagnoses are often made in tumors that lack unequivocal squamous and/or glandular differentiation. Considering the ambiguous etiologic, morphologic, and clinical features and outcomes associated with ASCs, we sought to redefine these tumors. We reviewed slides from 59 initially diagnosed ASCs (including glassy cell carcinoma and related lesions) to confirm an ASC diagnosis only in the presence of unequivocal malignant glandular and squamous differentiation. Select cases underwent immunohistochemical profiling as well as human papillomavirus (HPV) testing by in situ hybridization. Of the 59 cases originally classified as ASCs, 34 retained their ASC diagnosis, 9 were reclassified as pure invasive stratified mucin-producing carcinomas, 10 as invasive stratified mucin-producing carcinomas with other components (such as HPV-associated mucinous, usual-type, or ASCs), and 4 as HPV-associated usual or mucinous adenocarcinomas with benign-appearing squamous metaplasia. Two glassy adenocarcinomas were reclassified as poorly differentiated HPV-associated carcinomas based on morphology and immunophenotype. There were no significant immunophenotypic differences between ASCs and pure invasive stratified mucin-producing carcinomas with regard to HPV and other markers including p16 expression. Although limited by a small sample size, survival outcomes seemed to be similar between all groups. ASCs should be diagnosed only in the presence of unequivocal malignant glandular and squamous differentiation. The 2 putative glassy cell carcinomas studied did not meet our criteria for ASC and categorizing them as such should be reconsidered.

Trefoil Factor 2 (TFF2) as a Surrogate Marker for Endocervical Gastric-type Carcinoma.

Gastric-type carcinoma (GAS) is the most common human papilloma virus-independent endocervical adenocarcinoma (ECA), characterized by an aggressive behavior. Trefoil factor 2 (TFF2) is a mucin-associated peptide expressed in normal gastric but not endocervical glands. This study was carried out to investigate whether TFF2 could be a surrogate marker to separate GAS from other types of ECA. ECAs from 9 international institutions were reviewed for consensus histotype. Of them, expression of TFF2 was immunohistochemically examined compared with that of HIK1083, using whole sections of 50 ECAs (10 GASs and 40 non-GASs) and 179 ECAs (24 GASs and 155 non-GASs) with tissue microarrays (TMAs). TMAs were assessed to simulate assessment of immunohistochemical stains in small biopsies. Both markers were similarly scored, and any cytoplasmic/membranous staining of >5% of tumor cells was considered positive. Of 50 ECAs with whole sections, TFF2 was significantly more frequently expressed in GASs (8/10) compared with non-GASs (5/40) (P<0.01). In 179 ECAs with TMAs, TFF2 was also significantly more frequently expressed in GASs (7/24) compared with non-GASs (4/155) (P<0.01). There was no significant difference in specificity among the 2 markers. Double positivity for TFF2 and HIK1083 in ECAs was highly specific in separating GASs from non-GAS (P<0.01). A significantly smaller percentage of GASs were TFF2 positive in TMAs than in whole sections (P<0.01). Our results suggest that TFF2 is a promising marker, along with HIK1083, to confirm a diagnosis of GAS. This marker may be negative in small biopsies, indicating the necessity of using other exclusionary markers in combination with rigorous morphologic review and extensive sampling in resection specimens.

Clinicopathologic Association and Prognostic Value of MELF Pattern in Invasive Endocervical Adenocarcinoma (ECA) as Classified by IECC.

Microcystic, elongated, and fragmented (MELF) pattern of myometrial invasion is correlated with lymphovascular invasion (LVI) and lymph node metastases in uterine endometrioid carcinoma but has not been described in endocervical adenocarcinoma (ECA). A total of 457 ECAs were collected, and clinical/morphologic parameters correlated with follow-up data. Potential associations between MELF pattern and age, human papillomavirus status, tumor size/grade, LVI, lymph node metastases, Silva pattern were analyzed. Statistical analyses of overall survival (OS), disease-free survival, progression-free survival (PFS) were conducted using Kaplan-Meier analysis, and compared using the Log-rank test. Of 292 ECAs analyzed, 94 (32.19%) showed MELF invasion pattern (MELF-positive). Significant statistical correlation was found between MELF-positive and tumor size (P=0.0017), LVI (P=0.007), Silva pattern (P=0.0005); age, human papillomavirus status, tumor grade, lymph node metastases did not correlate. Fifty-five of 292 patients recurred (18.83%): 18/94 (19.14%) MELF-positive, 37/198 (18.68%) MELF-negative. PFS in MELF-positive: 77.2% and 64.5% at 5 and 10 yr, respectively; PFS in MELF-negative: 82% and 68.5% at 5 and 10 yr, respectively. On multivariate analysis for PFS and other prognostic parameters, only LVI was statistically significant (P=0.001). OS in MELF-positive was 86% and 74.1% at 5 and 10 yr, respectively; OS in MELF-negative, was 89.7% and 86% at 5 and 10 yr, respectively. Median survival was worse in MELF-positive (199.8 mo) versus MELF-negative (226.1 mo); this was not statistically significant. On multivariate analysis for OS and other prognostic parameters, only tumor stage was statistically significant (P=0.002). In ECAs, MELF is not independently associated with survival. Pathologic characteristics of MELF-positive (size, LVI, Silva pattern) versus MELF-negative tumors differ significantly.

Presence of tumor cells in the vagina during surgical treatment could be the source of vaginal recurrence in patients with endometrial carcinoma - A pilot prospective study.

BACKGROUND: The commonest site of recurrence in endometrial cancer (EC) is the vagina, with a rate of 16%. The aim of this study was to determine if vaginal recurrences in EC patients could develop due to contamination of the vagina with glandular tumor cells dropping off on polypoid, large size EC or tumors involving the endocervix, through manipulation of the uterus during surgery. METHODS: This pilot prospective study included 10 consecutive patients with EC, surgically treated with hysterectomy and additional lymphadenectomy according to stage. In every case, 2 proximal vaginal smears were collected before and during the hysterectomy procedure. All smears underwent Papanicolaou staining and the presence of atypical glandular cells in the smears was correlated with clinico-pathological parameters. RESULTS: Residual tumor was identified on the surgical specimen in the 10 cases; the tumor characteristics were large size (median 6 cm), polypoid type (80%), infiltrating the cervix (70%), and infiltrating more than half of the myometrium (60%). The smears obtained from the vagina showed that five cases (50%) presented tumor cells of glandular type in all smears (before and during the surgery), while in 3 cases (30%) the smears were negative for tumor cells preoperatively, but positive in the perioperative smears. CONCLUSIONS: Our results suggest that the vagina is most often contaminated preoperatively due to bleeding; however, the vaginal wound may also be contaminated perioperatively. We propose a change in the surgical procedure, which is easy to perform and inexpensive compared to postsurgical vaginal radiotherapy.

Cervical adenosquamous carcinoma: detailed analysis of morphology, immunohistochemical profile, and clinical outcomes in 59 cases.

Although 2014 World Health Organization criteria require unequivocal glandular and squamous differentiation for a diagnosis of cervical adenosquamous carcinoma, in practice, adenosquamous carcinoma diagnoses are often made in tumors that lack unequivocal squamous and/or glandular differentiation. Considering the ambiguous etiologic, morphological, and clinical features and outcomes associated with adenosquamous carcinomas, we sought to redefine these tumors. We reviewed slides from 59 initially diagnosed adenosquamous carcinomas (including glassy cell carcinoma and related lesions) to confirm an adenosquamous carcinoma diagnosis only in the presence of unequivocal malignant glandular and squamous differentiation. Select cases underwent immunohistochemical profiling as well as human papillomavirus (HPV) testing by in situ hybridization. Of the 59 cases originally classified as adenosquamous carcinomas, 34 retained their adenosquamous carcinoma diagnosis, 9 were reclassified as pure invasive stratified mucin-producing carcinomas, 10 as invasive stratified mucin-producing carcinomas with other components (such as HPV-associated mucinous, usual-type, or adenosquamous carcinomas), and 4 as HPV-associated usual or mucinous adenocarcinomas with benign-appearing squamous metaplasia. Two glassy cell carcinomas were reclassified as poorly differentiated usual-type carcinomas based on morphology and immunophenotype. There were significant immunophenotypic differences between adenosquamous carcinomas and pure invasive stratified mucin-producing carcinomas with regard to HPV (p < 0.0001), PAX8 (p = 0.038; more in adenosquamous carcinoma), p40 (p < 0.0001; more in adenosquamous carcinoma), p63 (p = 0.0018; more in adenosquamous carcinoma) and MUC6 (p < 0.0001; less in adenosquamous carcinoma), HNF-1beta (p = 0.0023), vimentin (p = 0.0003), p53 (p = 0.0004), and CK7 (p = 0.0002) expression. Survival outcomes were similar between all groups. Adenosquamous carcinomas should be diagnosed only in the presence of unequivocal malignant glandular and squamous differentiation. The two putative glassy cell carcinomas studied did not meet our criteria for adenosquamous carcinoma, and categorizing them as such should be reconsidered.

Breast Sarcomas-How Different Are They from Breast Carcinomas? Clinical, Pathological, Imaging and Treatment Insights.

Breast sarcoma (BS) is a very rare and poorly studied condition. This has led to a lack of studies with a high level of evidence and to low efficacy of current clinical management protocols. Here we present our experience in treating this disease in the form of a retrospective case series study including discussion of clinical, imaging, and pathological features and treatment. We also compare the main clinical and biological features of six cases of BS (phyllodes tumors were excluded) with a cohort of 184 patients with unilateral breast carcinoma (BC) from a previous study performed at our institution. Patients with BS were diagnosed at a younger age, presented no evidence of lymph node invasion or distant metastases, had no multiple or bilateral lesions, and underwent a shorter length of hospital stay versus the breast carcinoma group. Where recommended, adjuvant chemotherapy consisted of an anthracycline-containing regimen, and adjuvant external radiotherapy was delivered in doses of 50 Gy. The comparison data obtained from our BS cases and the ones with BC revealed differences in diagnosis and treatment. A correct pathological diagnosis of breast sarcoma is essential for the right therapeutic approach. We still have more to learn about this entity, but our case series could add value to existing knowledge in a meta-analysis study.

Incidence and Clinicopathologic Characteristics of Human Papillomavirus-independent Invasive Squamous Cell Carcinomas of the Cervix: A Morphologic, Immunohistochemical, and Human Papilloma-Virologic Study of 670 Cases.

We aimed to determine the frequency of human papillomavirus-independent (HPVI) cervical squamous cell carcinoma (SCC) and to describe clinicopathologic characteristics. Among 670 patients with surgically treated SCCs in an established multi-institutional cohort, 447 had available tissue. Tissue microarrays were constructed and studied by in situ hybridization (ISH) for high-risk and low-risk human papillomavirus (HPV) mRNA and immunohistochemistry for p16 and p53. Tumors were HPVI if negative by HPV ISH and they failed to show diffuse p16 positivity by immunohistochemistry, and human papillomavirus-associated (HPVA) if positive by HPV ISH. Ten HPVI SCCs and 435 HPVA SCCs were identified; 2 cases were equivocal and excluded from analysis. The overall rate of HPVI SCC was low (2%) but was higher among older patients (7% in patients above 60 y of age and 17% in patients above 70 y of age). Compared with HPVA, patients with HPVI SCC were significantly older (median age, 72 vs. 49, P <0.001) and diagnosed at a higher stage (40% vs. 18% with stage III/IV disease, P =0.055). p53 expression was varied; 2 cases (20%) had null expression and 8 (80%) had wild-type expression. HPVI SCCs were heterogenous, with keratinizing, nonkeratinizing, and warty morphologies observed. Several cases had a precursor lesion reminiscent of differentiated vulvar intraepithelial neoplasia, with prominent basal atypia and hypereosinophilia or a basaloid-like morphology. Two patients (20%) had distant recurrences within 12 months, and 3 (30%) died of disease during follow-up. HPVI SCCs are rare tumors that are more common among older patients with higher stage disease and have important clinical and histologic differences from HPVA SCCs.

Postoperative Quality Assessment Score Can Select Patients with High Risk for Locoregional Recurrence in Colon Cancer.

BACKGROUND: Monitoring surgical quality has been shown to reduce locoregional recurrence (LRR). We previously showed that the arterial stump length (ASL) after complete mesocolic excision (CME) is a reproducible quality instrument and correlates with the lymph-node (LN) yield. We hypothesized that generating an LRR prediction score by integrating the ASL would predict the risk of LRR after suboptimal surgery. METHODS: 502 patients with curative resections for stage I-III colon cancer were divided in two groups (CME vs. non-CME) and compared in terms of surgical data, ASL-derived parameters, pathological parameters, LRR and LRR-free survival. A prediction score was generated to stratify patients at high risk for LRR. RESULTS: The ASL showed significantly higher values (50.77 mm ± 28.5 mm) with LRR vs. (45.59 mm ± 28.1 mm) without LRR (p < 0.001). Kaplan-Meier survival analysis showed a significant increase in LRR-free survival at 5.58 years when CME was performed (Group A: 81%), in contrast to non-CME surgery (Group B: 67.2%). CONCLUSIONS: The prediction score placed 76.6% of patients with LRR in the high-risk category, with a strong predictive value. Patients with long vascular stumps and positive nodes could benefit from second surgery to complete the mesocolic excision.

Uterine Epithelioid Trophoblastic Tumor in a 44-Year-Old Woman: A Diagnostic Dilemma.

BACKGROUND: Epithelioid trophoblastic tumor (ETT) is a rare and newly defined disease, which most commonly occurs in women of reproductive age and can be a sequela of any gestational event. ETT can be present in both intrauterine and extrauterine sites. CASE REPORT: A woman of reproductive age, without specific comorbidities and with a single pregnancy and natural childbirth eight years ago, was diagnosed initially with poorly differentiated pleomorphic leiomyosarcoma on the hemostatic uterine curettage. CONCLUSION: Our case highlights that ETT presents a diagnostic challenge due to its rarity and histologic resemblance to other pathologies. Misdiagnosis delays effective treatment and affects survival. To date, only 8 cases of ETT of the uterus without previous gestational event and normal human chorionic gonadotropin (ß-HCG) levels in a 60-year literature survey have been reported.

Clinical, histopathological and immunohistochemical features of glomus tumor of the nail bed.

PURPOSE: Glomus tumors account for 1-4% of benign hand tumors. In 65% of cases, it is located in the nail bed. Its rarity makes misdiagnosis problems relatively common. Symptomatology is characterized by the hallmark symptomatic triad. Imaging investigations may guide the diagnosis, but the diagnosis is made by pathological examination doubled by immunohistochemical (IHC) markers. PATIENTS, MATERIALS AND METHODS: We studied a group of seven female patients, aged 28 to 56 years. Clinical examination revealed the presence of the characteristic symptomatic triad. Ultrasound imaging tests were performed. RESULTS: Anatomopathological examination made a diagnosis of glomus tumor in all seven cases. IHC staining showed that tumor cells were positive for alpha-smooth muscle actin (α-SMA) and h-caldesmon in all seven cases and negative for cluster of differentiation 34 (CD34) in 72.14%. IHC stainings for p63, S100, cytokeratin (CK) AE1∕AE3 were negative in all cases. The clinical diagnosis completed by ultrasonography was histopathologically confirmed in all cases. CONCLUSIONS: Although the glomus tumor is a rare lesion, we need to be familiar with it because a diagnostic delay also implies a treatment delay which will lead to amplified suffering and even real disability due to the high-intensity pain in these cases.

Nonasthmatic eosinophilic bronchitis in an ulcerative colitis patient - a putative adverse reaction to mesalazine: A case report and review of literature.

BACKGROUND: Lung and airway involvement in inflammatory bowel disease are increasingly frequently reported either as an extraintestinal manifestation or as an adverse effect of therapy. CASE SUMMARY: We report a case of a patient with ulcerative colitis controlled under mesalazine treatment who presented with chronic cough and hemoptysis. Chest computed tomography and bronchoscopy findings supported tracheal involvement in ulcerative colitis; pathology examination demonstrated an unusual eosinophil-rich inflammatory pattern, and together with clinical data, a nonasthmatic eosinophilic bronchitis diagnosis was formulated. Full recovery was observed within days of mesalazine discontinuation. CONCLUSION: Mesalazine-induced eosinophilic respiratory disorders have been previously reported, generally involving the lung parenchyma. To the best of our knowledge, this is the first report of mesalamine-induced eosinophilic involvement in the upper airway.

Calcific uremic arteriolopathy (calciphylaxis) calls into question the validity of guidelines of diagnosis and treatment.

Background: Calciphylaxis is associated with end-stage renal failure or kidney transplant, although, cases of non-uremic calciphylaxis have been reported. It is a rare disorder, with high mortality, characterized by vascular calcification within cutaneous vessels; vascular calcification can occur in other organs, besides skin, like heart, lung, or pancreas, which is named visceral calciphylaxis.Objective: The purpose was to review current knowledge regarding diagnosis and therapeutic approach to cutaneous calciphylaxis.Methods: A literature review has been conducted associated to word "calciphylaxis".Results: The diagnosis is based mainly on clinical features and histologic findings. Therapeutic options are still controversial.Conclusions: Cutaneous calciphylaxis is a puzzling disease, with a challenging diagnosis, and a complex treatment, which requires a multidisciplinary team and expertise.

Idiopathic tenosynovitis with rice bodies.

PURPOSE: Idiopathic tenosynovitis with rice bodies is a rare disease and its non-association with rheumatic diseases, tuberculosis infection or trauma is reported only in few cases in literature. PATIENTS, MATERIALS AND METHODS: Our study presents a series of five patients diagnosed with tenosynovitis with rice bodies at the flexor tendons of the upper limb. Medical history revealed no associated disease or trauma. Disease duration ranged between two months and four years, two patients presenting symptoms of acute carpal tunnel and three patients tumor mass. In one case, the tumor measured 210 mm in length and a tendon rupture was suspected. Laboratory and imaging investigations could not establish a specific associated pathology and a preoperative diagnosis. Surgical treatment consisting of synovectomy was performed in all patients. RESULTS: In all five cases, intraoperative appearance could easily determine the presence of rice bodies. Histopathological examination revealed typical aspect for rice bodies and make the diagnosis possible without the need for other more laborious processing (immunohistochemistry). The amount of rice bodies was directly proportional to disease duration. In all cases, the recovery was complete. After a median 30.4-month follow-up, no recurrence was detected. Subsequently performed laboratory investigations and specific tests did not reveal tuberculosis infection, rheumatic disease, or other diseases. CONCLUSIONS: This is the largest series of patients with idiopathic tenosynovitis with rice bodies and the bigger tumor mass reported to date. Synovectomy with removal of all rice bodies represents the optimal treatment. A longer disease course may be associated with a larger number of rice bodies, which may be associated with tendon rupture. The etiopathogenesis remains unclear, further studies being necessary to establish it.

Invasive Stratified Mucin-producing Carcinoma (ISMC) of the Cervix: A Study on Morphologic Diversity.

Invasive stratified mucin-producing carcinoma (ISMC) is a recently described tumor with similar morphology to the stratified mucin-producing intraepithelial lesion. Stratified mucin-producing intraepithelial lesion and ISMC likely arise from human papillomavirus (HPV)-infected reserve cells in the cervical transformation zone that retain their pluripotential ability to differentiate into various architectural and cytologic patterns. This is important, as small studies have suggested that ISMC may be a morphologic pattern associated with more aggressive behavior than usual HPV-associated adenocarcinoma. We sought to study the morphologic spectrum of this entity and its associations with other, more conventional patterns of HPV-associated carcinomas. Full slide sets from 52 cases of ISMC were reviewed by an international panel of gynecologic pathologists and classified according to the new International Endocervical Criteria and Classification system. Tumors were categorized as ISMC if they demonstrated stromal invasion by solid nests of neoplastic cells with at least focal areas of mucin stratified throughout the entire thickness, as opposed to conventional tall columnar cells with luminal gland formation. Tumors comprising pure ISMC, and those mixed with other morphologic patterns, were included in the analysis. Twenty-nine pure ISMCs (56%) and 23 ISMCs mixed with other components (44%) were identified. Other components included 13 cases of usual-type adenocarcinoma, 6 adenosquamous carcinoma, 3 mucinous-type adenocarcinoma, 1 high-grade neuroendocrine carcinoma. ISMC displayed architectural diversity (insular, lumen-forming, solid, papillary, trabecular, micropapillary, single cells) and variable cytologic appearance (eosinophilic cytoplasm, cytoplasmic clearing, histiocytoid features, glassy cell-like features, signet ring-like features, bizarre nuclei, squamoid differentiation). Awareness of the spectrum of morphologies in ISMC is important for accurate and reproducible diagnosis so that future studies to determine the clinical significance of ISMC can be conducted.

Nail bed solitary neurofibroma: A case report and literature review.

RATIONALE: Nail bed solitary neurofibroma is an extremely rare tumor, with only 9 cases recorded in the literature so far. PATIENT CONCERN: We present the case of a 42-year-old female patient, with a history of a slowly growing tumor in the nail bed of the left index and no clinical features of type I neurofibromatosis. DIAGNOSIS: Nail bed solitary neurofibroma. INTERVENTION: The tumor was surgically removed and the pathology examination established the diagnosis of neurofibroma. OUTCOMES: The postoperative outcome was good, with no recurrence 12 months after surgery. LESSONS: We present the rarity of this type of tumor localized in the nail bed, taking into consideration the only 9 cases recorded in the literature. Nail bed solitary neurofibroma should be also included in the differential diagnosis of a nail bed tumor.

Challenges in management of male breast adenomioepithelioma with malignant behavior: Case report.

RATIONALE: Male adenomyoepithelioma of the breast with malignant features is a rare tumor with only one previous case reported in the literature over 25 years ago. PATIENT CONCERNS: We report the case of a 63-year-old man admitted to our Oncology Institute with a painless tumor mass of 6 cm in the left breast with no additional regional lymph nodes. Ultrasound revealed a complex cystic tumor mass of 60 mm in the left breast, with both anechoic (cystic) and echogenic (solid) components, with ill-defined margin. DIAGNOSES: Extemporaneous assessment showed a solid (invasive) papillary intracystic carcinoma. Definitive pathology examination revealed the presence of a breast malignant adenomyoepithelioma. INTERVENTIONS: Based on the extemporaneous assessment, wide tumor excision was performed. The tumor board decided to continue treatment with adjuvant anthracycline-based chemotherapy. OUTCOMES: After 6 years of follow-up, the patient is cancer-free. No chronic side effects were noted. LESSONS: Because this pathology is extremely rare, no guidelines are available for its therapeutic approach. All decisions regarding patient management should be made by a multi-disciplinary team and can only be based on clinical experience and the few cases reported in female patients.

Multiple versus unifocal breast cancer: clinicopathological and immunohistochemical differences.

Multiple breast cancer (MBC) is a controversial topic due to the lack of a consensus regarding its definition, classification issues and imprecise management recommendations in current reference guidelines. In four years, 756 patients with breast cancer (BC) were surgically treated in our Unit, 91 (12.03%) of them being pathologically diagnosed as MBCs. We present the results of our retrospective case-control study that performed a comparison between the clinicopathological characteristics and immunohistochemical (IHC) profiles of our MBC group versus a control group, represented by a sample of 184 cases randomly chosen from those with unifocal breast cancer (UBC). Starting from the premise of increased biological aggressivity of MBC, showed by several reports, we proposed to research the possible differences between these groups and to highlight their potential predictive and/or prognostic value. We found that MBC patients have a poorer prognosis than UBC ones - younger age at diagnosis [more cases less than 50 years old (p=0.03)], a lower frequency of T1 and a higher rate of T3 tumors [when using aggregate tumor size measuring method (p<0.001)], fewer node-negative (N0) cases (p=0.046) and a higher frequency of mucinous breast carcinoma (p=0.026). It worth mentioning that we obtained lower rates of poorly differentiated (G3) tumors (p=0.022) in the MBC group, this result being opposite to those found by other researchers. Our study also revealed a higher rate of human epidermal growth factor receptor 2 (HER2∕neu)-type cases in MBC group (p=0.022), these patients having the chance to benefit from treatment with monoclonal antibodies, with a better outcome than patients with triple-negative type. We registered significantly lower progesterone receptor (PR) positivity rates in patients with MBC, thus having a negative predictive value by showing a worse response to hormone-based therapies. Besides, we found heterogeneity of IHC features among tumor foci in MBC that may influence the therapeutic decisions. Our results sustain that MBC is biologically a more aggressive type of mammary neoplasia requiring a more particular therapeutic approach.