Paraneoplastic Syndromes in Patients with Keratinocyte Skin Cancer

A variety of well-characterized cutaneous paraneoplastic syndromes (PNS) are diagnosed during internal malignancies; however, the spectrum of keratinocyte skin neoplasms (KSC) related to PNS is still obscure. The aim of the present review is to compile and evaluate the literature data on PNS associated with a keratinocyte skin neoplasm (KSC). Employing Pubmed, MEDLINE was searched for KSC-associated PNS reports. Forty relevant entries were assembled, reporting a total of 41 PNS cases associated with a KSC (34 male). No review paper compiling this topic was found. Six distinct PNS entities were identified, and malignancy associated hypercalcemia (MAH; 78%), anemia (10%) and Bazex syndrome (5%) were the most frequently reported among them. 85% of the PNS were reported in association with SCC, 10% with BCC, and the rest with adnexal tumors. The median age of the patients at the time of PNS diagnosis was 58 years (range: five–83 years). In most cases the PNS was diagnosed either concurrently or after the KSC diagnosis. KSC predisposing conditions, as scars (22%) or hidradenitis suppurativa (20%), were reported in >70% of the PNS cases. Most PNS resolved after KSC treatment. In conclusion, PNS of a rather limited spectrum of entities are reported in association with KSC. They also seem to be rare, possibly reflecting a limited capacity of KSC to provoke overt PNS.

NUTM1-Rearranged Neoplasms: A Heterogeneous Group of Primitive Tumors with Expanding Spectrum of Histology and Molecular Alterations: An Updated Review

Nuclear protein of testis (NUT), a protein product of the NUTM1 gene (located on the long arm of chromosome 15) with highly restricted physiologic expression in post-meiotic spermatids, is the oncogenic driver of a group of emerging neoplasms when fused with genes involved in transcription regulation. Although initially identified in a group of lethal midline carcinomas in which NUT forms fusion proteins with bromodomain proteins, NUTM1-rearrangement has since been identified in tumors at non-midline locations, with non-bromodomain partners and with varied morphology. The histologic features of these tumors have also expanded to include sarcoma, skin adnexal tumors, and hematologic malignancies that harbor various fusion partners and are associated with markedly different clinical courses varying from benign to malignant. Most of these tumors have nondescript primitive morphology and therefore should be routinely considered in any undifferentiated neoplasm. The diagnosis is facilitated by the immunohistochemical use of the monoclonal C52 antibody, fluorescence in situ hybridization (FISH), and, recently, RNA-sequencing. The pathogenesis is believed to be altered expression of oncogenes or tumor suppressor genes by NUT-mediated genome-wide histone modification. NUTM1-rearranged neoplasms respond poorly to classical chemotherapy and radiation therapy. Targeted therapies such as bromodomain and extraterminal domain inhibitor (BETi) therapy are being developed. This current review provides an update on NUTM1-rearranged neoplasms, focusing on the correlation between basic sciences and clinical aspects.

The Proliferating and Malignant Proliferating Trichilemmal Cyst: An Anatomo-Clinical Study of Three Cases

<b><i>Background:</i></b> The proliferating and malignant proliferating trichilemmal cysts (MPTC) are rare adnexal tumors. We report 3 cases through which we will detail the anatomo-clinical characteristics of these tumors. <b><i>Cases:</i></b> Two patients, 60 and 56 years old, consulted for multiple scalp nodules, one of which had changed with the appearance of a central ulceration. The removal of the remaining scalp nodules was in favor of PTCs. The third patient presented with an ulcerative lesion occupying the vertex. Skin biopsy found trichilemmal-type keratinization associated with areas of necrosis concluding with a MPTC. <b><i>Discussion:</i></b> The PTC is a transitional form between the trichilemmal cyst (TC) and the MPTC. The increase in the size of a TC and ulceration are sufficient signals to suspect this evolution.

POROCARCINOMA OVER SCALP: A RARE ENTITY

Porocarcinomas are aggressive adnexal tumors with a rare incidence. They are usually seen as a nodular or infiltrating growth over the lower extremities, infrequently over the scalp. They are thought to be arising from a pre-existing lesion and with a long clinical history. Treatment of choice is surgical resection with histopathologically confirmed negative margins. There are chances of local recurrence; hence a regular follow-up is must in these cases. Hereby we present a case of 42 year old male with 2 year history of growth over the right temporo-parietal region of the scalp. Histological confirmation of the diagnosis was done after wide local excision of the tumor. Porocarcinomas are mostly likely to be misdiagnosed clinically; therefore a histopathological correlation is necessary for the confirmation of diagnosis and further management of the patient.

Indirect comparison of the diagnostic performance of 18F-FDG PET/CT and MRI in differentiating benign and malignant ovarian or adnexal tumors: a systematic review and meta-analysis

Objective To compare the value of fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) and magnetic resonance imaging (MRI) in differentiating benign and malignant ovarian or adnexal tumors. Materials and methods English articles reporting on the diagnostic performance of MRI or 18F-FDG PET/CT in identifying benign and malignant ovarian or adnexal tumors published in PubMed and Embase between January 2000 and January 2021 were included in the meta-analysis. Two authors independently extracted the data. If the data presented in the study report could be used to construct a 2 × 2 contingency table comparing 18F-FDG PET/CT and MRI, the studies were selected for the analysis. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of the included studies. Forest plots were generated according to the sensitivity and specificity of 18F-FDG PET/CT and MRI. Results A total of 27 articles, including 1118F-FDG PET/CT studies and 17 MRI studies on the differentiation of benign and malignant ovarian or adnexal tumors, were included in this meta-analysis. The pooled sensitivity and specificity for 18F-FDG PET/CT in differentiating benign and malignant ovarian or adnexal tumors were 0.94 (95% CI, 0.87–0.97) and 0.86 (95% CI, 0.79–0.91), respectively, and the pooled sensitivity and specificity for MRI were 0.92 (95% CI: 0.89–0.95) and 0.85 (95% CI: 0.79–0.89), respectively. Conclusion While MRI and 18F-FDG PET/CT both showed to have high and similar diagnostic performance in the differential diagnosis of benign and malignant ovarian or adnexal tumors, MRI, a promising non-radiation imaging technology, may be a more suitable choice for patients with ovarian or accessory tumors. Nonetheless, prospective studies directly comparing MRI and 18F-FDG PET/CT diagnostic performance in the differentiation of benign and malignant ovarian or adnexal tumors are needed.

Biphasic Sarcomatoid Sweat Gland Carcinoma With Ductal Epithelial And Spindled Myoepithelial Cell Components (Malignant Mixed Tumor Of Skin)

Introduction/Objective Sweat gland carcinomas are a group of malignant skin adnexal tumors that are difficult to diagnose due to their rarity, wide morphologic variation, and limited literature on diagnosis and classification. These tumors may appear bland and morphologically resemble benign skin adnexal tumors, or may appear poorly differentiated and mimic metastatic carcinoma especially from a breast primary. Biphasic sweat gland carcinomas are an even rarer entity, with only few cases reported in literature, and have been described to consist of a well- differentiated ductal epithelial component and a poorly differentiated, sarcomatoid, spindle cell component. Methods/Case Report Our case report describes a 53 year old female referred to our institution for diagnosis of an excised skin lesion of the right upper arm, which had been slowly growing for 8 years. The histology revealed a biphasic malignant neoplasm involving the dermis and subcutis. The tumor consisted of an epithelial cell component with glandular and squamoid morphology and positive for CK5/6, CK7, and CAM5.2, and a spindled myoepithelial cell component with sarcomatoid morphology and positive for S100, vimentin, and p63. Stains for CK20, ER, PR, PAX8, CEA, and TTF1 were negative. The histological and clinical findings favored a primary skin adnexal tumor, rather than a metastatic lesion. The patient underwent wide local excision of the lesion given that margins of the original excision were indeterminate. The histology of this re-excision demonstrated the same biphasic tumor with ductal epithelial and sarcomatoid myoepithelial cell components positive for the same stains. Although margins were negative in this re-excision, 3-4 months later, the patient developed dyspnea with multiple new pulmonary and hilar masses discovered on imaging, and new-onset headache with a frontal lobe mass discovered on brain imaging. These masses were biopsied/resected, and revealed to be metastases of the original cutaneous tumor positive for the same markers. Results (if a Case Study enter NA) NA Conclusion This case report describes a rare, diagnostically challenging case of a biphasic sweat gland carcinoma with ductal epithelial and sarcomatoid myoepithelial cell components, which demonstrated aggressive behavior with distant metastasis. These tumors are a clinicopathological quandary given their rarity and the paucity of literature on their characterization.

NUTM1-Rearranged Neoplasms: A Heterogeneous Group of Primitive Tumors with Expanding Spectrum of Histology and Molecular Alterations: An Updated Review

Nuclear protein of testis (NUT), a protein product of the NUTM1 gene (located on the long arm of chromosome 15) with highly restricted physiologic expression in post-meiotic spermatids, is the oncogenic driver of a group of emerging neoplasms when fused with genes involved in transcription regulation. Although initially identified in a group of lethal midline carcinomas in which NUT forms fusion proteins with bromodomain proteins, NUTM1-rearrangement has since been identified in tumors at non-midline locations, with non-bromodomain partners and with varied morphology. The histologic features of these tumors have also expanded to include sarcoma, skin adnexal tumors, and hematologic malignancies that harbor various fusion partners and are associated with markedly different clinical courses varying from benign to malignant. Most of these tumors have nondescript primitive morphology and therefore should be routinely considered in any undifferentiated neoplasm. The diagnosis is facilitated by the immunohistochemical use of the monoclonal C52 antibody, fluorescence in situ hybridization (FISH), and, recently, RNA-Sequencing. The pathogenesis is believed to be altered expression of oncogenes or tumor suppressor genes by NUT-mediated genome-wide histone modification. NUTM1-rearranged neoplasms respond poorly to classical chemotherapy and radiation therapy. Targeted therapies such as bromodomain and extraterminal domain inhibitor (BETi) therapy are being developed. This current review provides an update of NUTM1-rearranged neoplasms, focusing on the correlation between basic sciences and clinical aspects.