Birt-Hogg-Dubé Syndrome and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome: An Effective Multidisciplinary Approach to Hereditary Renal Cancer Predisposing Syndromes

AimWe aimed to describe and analyse clinical features, characteristics, and adherence to surveillance guidelines in an Australian Birt-Hogg-Dubé syndrome (BHD) and hereditary leiomyomatosis and renal cell cancer (HLRCC) cohort.MethodsAll identified patients with a diagnosis of BHD or HLRCC at RBWH 01/01/2014-01/09/2019 were included (HREC/17/QRBW/276). All patients were initially assessed and counselled by a clinical geneticist and then referred to an adult nephrologist. Baseline and incidental clinical variables were extracted and analysed.ResultsFifty-seven patients were identified (28 BHD, 29 HLRCC) with a median age of 47 years. The median and cumulative follow-up were 1 and 99 years, respectively. Baseline renal MRI occurred in 40/57 patients, and 33/57 had regular MRI as per the national guidelines (eviQ). Of 18/57 without baseline imaging, nine were yet to have imaging, seven were lost follow-up, and two patients had logistic difficulties. RCC was diagnosed in 11/57 patients: two of 28 with BHD were diagnosed with RCC aged 73 and 77, both prior to commencement of surveillance. Nine of 29 patients with HLRCC were diagnosed with RCC (one of 29 during surveillance at 47 years of age) and eight of 29 prior to commencement of surveillance (11–55 years). Amongst BHD patients, cutaneous fibrofolliculomas were noted in 15 patients, lung cysts were detected in seven patients, spontaneous pneumothoraces in five patients, and parotid oncocytoma in two of 28. Amongst those with HLRCC, cutaneous leiomyomas were noted in 19/29, cutaneous leiomyosarcoma diagnosed in one of 29, and uterine fibroids in 13 female patients.ConclusionEvidence-based RCC screening in BHD and HLRCC cohort is feasible and able to identify incidental renal lesions. Multidisciplinary patient management enables expedited genetic counselling, diagnosis, longitudinal screening, and RCC management. The success of this clinical model warrants consideration of undertaking longitudinal screening of BHD and HLRCC patients by nephrologists.

Zosteriform cutaneous leiomyoma: a case report

<p class="abstract">Cutaneous leiomyomas are rare, benign soft tissue tumors arising from smooth muscles of the skin and comprise of three distinct subtypes, namely piloleiomyoma, angioleiomyoma and genital leiomyoma. Piloleiomyomas can present as solitary form, multiple disseminated and zosteriform or segmental forms. Cutaneous leiomyomas are rare, of which zosteriform leiomyoma is not commonly encountered. Here we report an uncommon case of Type I zosteriform cutaneous leiomyoma in a middle-aged individual which was confirmed on histopathology. Patient was further started on nifedipine with significant symptomatic improvement. The patient is planned for surgical excision and long-term follow in view of its association with aggressive renal malignancy.</p>

Familial leiomyoma: a case report

<p class="abstract">Cutaneous leiomyomas are benign tumors that can be exquisitely painful. Comprise three distinct types such as piloleimyoma, angioleiomyoma, and genital leiomyoma. Piloleiomyomas, derived from arrector pili muscle, are solitary or multiple firm papulonodules located mostly on the extremities and trunk; genital leiomyomas, derived from dartoic, vulvar, or mammary smooth muscle, are solitary or papulonodules located on the scrotum, vulva, or nipple; and angioleiomyomas, include solid, cavernous, or venous subtypes, are derived from the tunica media of small arteries and veins and typically present on the extremities. Excisional biopsy is required for diagnosing all cutaneous leiomyomas Histology shows interlacing fibers of spindle cells with moderate amounts of eosinophilic cytoplasm and a blunt-ended, elongated nucleus with perinuclear halos. Surgical excision is curative for cutaneous leiomyomas, with other management options including medical or destructive therapy. A 36-year-old male patient presented with a 13 years history of painful, multiple lesions over the back. Based on the histopathological examination, imaging, and past medical records, a diagnosis of familial leiomyoma was made. His brother had similar disease. The patient was started on tab gabapentin 300mg at night. Patient advised for carbon dioxide laser excision. The present case report has been reported for its interesting clinical presentations and rarity.</p>

Wilms’ Tumor 1 (WT1): A Novel Immunomarker of Dermatofibrosarcoma Protuberans—An Immunohistochemical Study on a Series of 114 Cases of Bland-Looking Mesenchymal Spindle Cell Lesions of the Dermis/Subcutaneous Tissues

Purpose: to investigate the immunohistochemical expression and distribution of Wilms’ tumor 1 (WT1) (transcription factor produced by the tumor suppressor gene of the same name) in a series of 114 cases of bland-looking mesenchymal spindle cell lesions of the dermis/subcutaneous tissues to establish whether this immunomarker is differentially expressed in dermatofibrosarcoma protuberans (DFSP) versus its potential morphological mimickers. Methods: This retrospective multi-centric immunohistochemical study included 57 DFSP cases, 15 dermatofibromas, 5 deep fibrous histiocytomas, 8 neurofibromas, 5 spindle cell lipomas, 8 dermal scars, 6 nodular fasciitis, 5 cutaneous leiomyomas and 5 solitary fibrous tumors. Among the 57 DFSP cases, 11 were recurrent lesions; 2 non-recurrent cases exhibited an additional “fibrosarcomatous” overgrowth and 1 recurrent and 2 primary tumors contained a minority of “giant cell fibroblastoma” components. Results: Most DFSP (95% of cases) exhibited cytoplasmic staining for WT1; 11/11 residual/recurrent tumors showed diffuse and strong WT1 cytoplasmic immunoreactivity; apart from neurofibromas, WT1 expression was lacking in all the other cases studied. Conclusions: The cytoplasmic expression of WT1 may be exploitable as a complementary diagnostic immunomarker to CD34 in confirming the diagnosis of DFSP and to better evaluate the residual/recurrent tumor component.

Cutaneous Leiomyomatosis – Case Report and Literature Review

Cutaneous leiomyomas are uncommon benign smooth muscle tumors that comprise of three distinct types such as piloleiomyoma, angioleiomyoma, and genital leiomyoma. The discovery in 2001 of the association between cutaneous leiomyomas, uterine leiomyomas in women, and an aggressive form of renal cell cancer (RCC) underscores the importance of accurate dermatologic diagnosis of CL so that appropriate cancer screening and counseling of patients and at-risk relatives can be instituted. The present case report will discuss the pathogenesis, clinical manifestations, diagnosis, and management of a piloleiomyoma.