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Histopathology Aug 2023Poroma is a benign adnexal neoplasm with differentiation towards the upper portion of the sweat gland apparatus. In 2019, Sekine et al. demonstrated recurrent...
AIMS
Poroma is a benign adnexal neoplasm with differentiation towards the upper portion of the sweat gland apparatus. In 2019, Sekine et al. demonstrated recurrent YAP1::MAML2 and YAP1::NUTM1 fusion in poroma and porocarcinoma. Follicular, sebaceous and/or apocrine differentiation has been reported in rare cases of poroma and whether these tumours constitute a variant of poroma or represent a distinctive tumour is a matter to debate. Herein we describe the clinical, immunophenotypic, and molecular features of 13 cases of poroma with folliculo-sebaceous differentiation.
METHODS AND RESULTS
Most of the tumours were located on the head and neck region (n = 7), and on the thigh (n = 3). All presented were adults with a slight male predilection. The median tumour size was 10 mm (range: 4-25). Microscopically, lesions displayed features of poroma with nodules of monotonous basophilic cells associated with a second population of larger eosinophilic cells. In all cases, ducts and scattered sebocytes were identified. Infundibular cysts were present in 10 cases. In two cases high mitotic activity was noted, and in three cases cytologic atypia and areas of necrosis were identified. Whole transcriptome RNA sequencing demonstrated in-frame fusion transcripts involving RNF13::PAK2 (n = 4), EPHB3::PAK2 (n = 2), DLG1::PAK2 (n = 2), LRIG1::PAK2 (n = 1), ATP1B3::PAK2 (n = 1), TM9SF4::PAK2 (n = 1), and CTNNA1::PAK2 (n = 1). Moreover, fluorescence in situ hybridisation (FISH) analysis revealed PAK2 rearrangement in an additional case. No YAP1::MAML2 or YAP1::NUTM1 fusion was detected.
CONCLUSION
Recurrent fusions involving the PAK2 gene in all analysed poroma with folliculo-sebaceous differentiation in this study confirms that this neoplasm represents a separate tumour entity distinct from YAP1::MAML2 or YAP1::NUTM1 rearranged poromas.
Topics: Male; Humans; Poroma; Transcription Factors; Sweat Gland Neoplasms; Cell Differentiation; p21-Activated Kinases; Sodium-Potassium-Exchanging ATPase; Membrane Proteins
PubMed: 37199682
DOI: 10.1111/his.14940 -
Histopathology Jan 2024Poroma is a benign sweat gland tumour showing morphological features recapitulating the superficial portion of the eccrine sweat coil. A subset of poromas may transform... (Review)
Review
Poroma is a benign sweat gland tumour showing morphological features recapitulating the superficial portion of the eccrine sweat coil. A subset of poromas may transform into porocarcinoma, its malignant counterpart. Poroma and porocarcinoma are characterised by recurrent gene fusions involving YAP1, a transcriptional co-activator, which is controlled by the Hippo signalling pathway. The fusion genes frequently involve MAML2 and NUTM1, which are also rearranged in other cutaneous and extracutaneous neoplasms. We aimed to review the clinical, morphological and molecular features of this category of adnexal neoplasms with a special focus upon emerging differential diagnoses, and discuss how their systematic molecular characterisation may contribute to a standardisation of diagnosis, more accurate classification and, ultimately, refinement of their prognosis and therapeutic modalities.
Topics: Humans; Poroma; Eccrine Porocarcinoma; Skin Neoplasms; Sweat Gland Neoplasms; Skin; Transcription Factors
PubMed: 37609771
DOI: 10.1111/his.15023 -
Diagnostics (Basel, Switzerland) Aug 2023Eccrine poroma (EP) is a relatively rare benign adnexal neoplasm that usually affects elderly patients. Its pathogenesis is still under investigation, but recent gene... (Review)
Review
Eccrine poroma (EP) is a relatively rare benign adnexal neoplasm that usually affects elderly patients. Its pathogenesis is still under investigation, but recent gene studies have revealed gene fusions as key incidences resulting in oncogenetic pathways. It often presents as a solitary, firm papule, mostly asymptomatic, located on the soles or palms. Due to its clinical and dermoscopic variability, it is characterized as the great imitator. We performed a literature review, aiming to summarize current data on the pathogenetic mechanisms, new dermoscopic features, and novel diagnostic tools that may aid in early diagnosis and proper management of this rare adnexal tumor. Furthermore, we reviewed the possible pathogenetic associations between EP and its malignant counterpart, namely eccrine porocarcinoma. This systematic approach may aid in understanding the pathogenetic mechanisms and how to use novel histopathologic markers and imaging methods to overcome the diagnostic dilemma of this rare tumor.
PubMed: 37627947
DOI: 10.3390/diagnostics13162689 -
Histopathology May 2024Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign...
AIMS
Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2-fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions.
METHODS AND RESULTS
Five patients were male and the median age was 79 years (ranges: 59-95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases.
CONCLUSION
Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.
PubMed: 38785043
DOI: 10.1111/his.15214 -
Journal of Drugs in Dermatology : JDD Jul 2023This case detailing a poroma in Fitzpatrick Type V skin presents gross, dermatoscopic, and histopathologic images that have not been adequately represented in the...
This case detailing a poroma in Fitzpatrick Type V skin presents gross, dermatoscopic, and histopathologic images that have not been adequately represented in the literature. Diagnosing poroma can be challenging and misdiagnoses can have tragic consequences. The scarcity of published poroma images in darker skin types can further complicate this problem. Mineroff J, Jagdeo J, Heilman E, et al. Poroma in a patient with Fitzpatrick type V skin. J Drugs Dermatol. 2023;22(7):690-691. doi:10.36849/JDD.7371.
Topics: Humans; Poroma; Skin; Skin Pigmentation; Sweat Gland Neoplasms
PubMed: 37410036
DOI: 10.36849/JDD.7371 -
Journal of Cutaneous Pathology Nov 2023Transcriptional repressor GATA binding 1 (TRPS1) is a transcription factor recently shown to play a role in the development of breast and liver cancer. Here, we evaluate...
BACKGROUND
Transcriptional repressor GATA binding 1 (TRPS1) is a transcription factor recently shown to play a role in the development of breast and liver cancer. Here, we evaluate TRPS1 immunoexpression in normal skin tissues and various cutaneous tumors.
METHODS
TRPS1 immunohistochemistry was performed in 109 cases of primary cutaneous tumors and 19 cases of metastatic carcinomas. TRPS1 expression was also evaluated in the normal skin tissues.
RESULTS
The normal epidermis was TRPS1-. In contrast, the eccrine apparatus, epithelial compartment of the hair follicles, hair papilla, sebaceous glands, and anogenital mammary-like glands were TRPS1+. In primary cutaneous tumors, TRPS1 positivity varied in poroma (2/3), nodular hidradenoma (4/5), spiradenoma (4/4), cutaneous mixed tumor (5/5), trichilemmal cyst (7/8), proliferating trichilemmal tumor (1/3), pilomatricoma (9/9), sebaceoma (2/5), extramammary Paget disease (13/13), sebaceous carcinoma (2/2), actinic keratosis (3/10), Bowen disease (7/12), and squamous cell carcinoma (1/5) cases. All cases of seborrheic keratosis, basal cell carcinoma, Merkel cell carcinoma, and malignant melanoma were TRPS1-. All metastatic breast carcinoma cases (8/8) were highly positive for TRPS1, while all but one of the other metastatic tumor cases were TRPS1-.
CONCLUSIONS
TRPS1 immunoexpression was observed in several skin appendages and cutaneous tumors.
PubMed: 37649299
DOI: 10.1111/cup.14523 -
The American Journal of Case Reports Dec 2023BACKGROUND Eyelid tumors belong to a diverse group of neoplasms ranging from benign lesions to malignant tumors. Poromas are common, benign, mostly unpigmented tumors of... (Review)
Review
BACKGROUND Eyelid tumors belong to a diverse group of neoplasms ranging from benign lesions to malignant tumors. Poromas are common, benign, mostly unpigmented tumors of the epidermal sweat duct unit, that usually grow slowly and occur in elderly people on the palms and soles. In most poroma cases some gene fusions were detected, which were caused by chromosomal aberrations. CASE REPORT We report the atypical case of a 30-year-old female patient suffering for more than 15 years from a solitary, polypoid, pigmented formation with a focal tuberous surface on the left lower eyelid. The lesion was not growing during the first years, but in the last 6 months before diagnosis its size more than doubled, finally reaching 12×14 mm. It was removed and histopathological analysis confirmed the diagnosis of a rare tumor - a poroma. There were no complications during healing and no recurrence was reported. CONCLUSIONS There have so far been only 9 reports of eyelid poromas, and the presented case significantly differed from the previous ones, as it appeared at an early age and showed rapid growth during a short time due to the war-related acute psychological stress. Moreover, it had unusual pigmentation and unpleasant smell. Reporting such untypical cases is clinically important because it is crucial to be aware of the diversity of eccrine poroma manifestation to distinguish it from malignant lesions.
Topics: Adult; Female; Humans; Diagnosis, Differential; Eyelids; Pigmentation Disorders; Poroma; Sweat Gland Neoplasms
PubMed: 38115572
DOI: 10.12659/AJCR.941975 -
Histopathology Nov 2023Metaplastic thymoma is a rare thymic tumour characterized by Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) gene fusions...
AIMS
Metaplastic thymoma is a rare thymic tumour characterized by Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) gene fusions resulting from an intrachromosomal inversion of chromosome 11. Immunohistochemistry with an antibody directed against the C-terminus of YAP1 has shown loss of expression in YAP1-rearranged vascular neoplasms, poromas, and porocarcinomas. This study aimed to validate an anti-YAP1 C-terminal antibody as an ancillary immunohistochemical marker for the diagnosis of metaplastic thymoma.
MATERIALS AND METHODS
Ten metaplastic thymomas were selected for the current study. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed to detect YAP1::MAML2 fusions. We then performed immunohistochemistry to detect YAP1 C-terminus expression in 10 metaplastic thymomas, 50 conventional thymomas (10 each of type A thymoma, type AB thymoma, type B1 thymoma, type B2 thymoma, and type B3 thymoma) and seven thymic carcinomas.
RESULTS
All 10 cases showed narrow split signals with a distance of nearly two signal diameters and sometimes had false-negative results in YAP1 and MAML2 break-apart FISH (BA-FISH). Abnormal colocalized signals of the YAP1::MAML2 fusion were observed in all 10 cases using fusion FISH (F-FISH) assays. Eight of 10 cases with adequate nucleic acids were successfully sequenced and all showed YAP1::MAML2 fusions; in two cases the fusions were detected by both DNA and RNA sequencing and in six cases by RNA sequencing only. YAP1::MAML2 fusion transcripts were identified in four cases by RT-PCR. Metaplastic thymoma showed loss of YAP1 C-terminus expression in all 10 (100%) cases. All other thymic neoplasms showed retained YAP1 C-terminus expression.
CONCLUSION
YAP1 C-terminus immunohistochemistry is a highly sensitive and specific ancillary marker that distinguishes metaplastic thymoma from its mimics. BA-FISH assays could not effectively detect YAP1::MAML2 fusions due to the proximity of the two genes. Loss of YAP1 C-terminus expression is a reliable surrogate for the detection of YAP1::MAML2 fusions in metaplastic thymoma.
Topics: Humans; Thymoma; In Situ Hybridization, Fluorescence; Transcription Factors; Thymus Neoplasms; Adaptor Proteins, Signal Transducing; Gene Rearrangement; Trans-Activators
PubMed: 37565303
DOI: 10.1111/his.15024