Sean K Lau’s research while affiliated with Kaiser Permanente and other places

The 2022-2023 mpox outbreak is a global worldwide concern, especially since the virus was previously mainly localized regionally in Central and West Africa. The infection is typically self-limiting and transmitted by close contact/exposure with infected material. Recent cases have been known to present atypically without prodromal symptoms and initially with skin lesions. The histopathology of mpox lesions is rarely reported. Here, we present two middle-aged males presenting initially with painless skin lesions confirmed for mpox by nucleic acid amplification assay. Skin biopsies of the lesion were available for clinicopathologic correlation. Histopathology demonstrated ulceration with viral cytopathologic changes.

Background: Distinction of superficial spreading melanoma (SSM) from compound nevi (CN) sometimes poses difficult diagnostic challenges. Herein, we studied cyclin D1 protein expression by immunohistochemistry in SSM and CN and evaluated the results by digital image analysis. Design: A total of 13 CN and 12 SSM cases were retrospectively reviewed and cyclin D1 immunohistochemistry was performed. Immunohistochemical stained slides were evaluated by digital imaging analysis that included quantification and staining intensity of the cyclin D1 expressing dermal cells. Results: Cyclin D1 expression was observed in all CN and SSM. CN-positive staining was present in 30% to 93% of the dermal nevocytes, more positive in the upper (mean 85%), than lower half (mean 57%). SSM-positive staining was present in 44% to 96% of the dermal lesion, more positive in the upper (mean 88%) than lower half (mean 49%). When analyzed based on 3+ strong staining intensity, similar regional differences in cyclin D1 expression were observed. Conclusions: Digital image analysis of Cyclin D1 expression showed no differences between CN and SSM. Quantity and regional distribution of cyclin D1 positivity were found to be similar in both lesions. Our findings argue against the routine use of cyclin D1 immunohistochemistry as a diagnostic tool for differentiating CN from SSM.

Background: Spitzoid melanocytic neoplasms are well known to be diagnostically challenging. Immunohistochemistry and molecular approaches have been used as ancillary diagnostic tests. Herein we investigate the use of PRAME immunohistochemistry (IHC) for the assessment of spitzoid melanocytic neoplasms. Methods: 10 Spitz nevi, 14 atypical Spitz tumors, and 11 spitzoid melanomas were retrieved and PRAME IHC was scored on a scale of 1-4 (in % quartiles). Intensity of staining was categorized as weak or strong. Cases with no staining received a score of 0. Positive lymph nodes from three spitzoid melanomas were also analyzed. Results: Spitz nevi, atypical Spitz tumors, and spitzoid melanomas had mean PRAME IHC scores of 1.20, 0.93, and 3.36 respectively. The percentage of cases with a score 3 or higher for each category of spitzoid neoplasms are as follows: Spitz nevus (20%), atypical Spitz tumor (0%), and spitzoid melanoma (82%). Among the spitzoid melanomas, 3 cases had positive sentinel lymph nodes which demonstrated PRAME score of 2, 4, and 4 in the metastatic deposits. Conclusions: Previous reports revealed PRAME IHC as useful to distinguish benign from malignant melanocytic lesions. The results presented here are concordant with the prior studies, but expand the application of this marker to Spitz nevi/tumors and spitzoid melanomas. The present findings suggest the potential diagnostic utility of PRAME IHC in the assessment of spitzoid melanocytic lesions, particularly in distinguishing spitzoid melanomas from Spitz nevi and atypical Spitz tumors. This article is protected by copyright. All rights reserved.

Cellular neurothekeoma is a cutaneous tumor with a distinctive histopathologic appearance characterized by a dermal based multinodular proliferation of epithelioid to spindled cells. Although the tumor may show varying amounts of myxoid stroma, extensive myxoid change is uncommon. The tumor typically presents as a solitary nodule with a predilection for the head and neck and upper limbs; examples of multiple cellular neurothekeomas are decidedly rare. The present report describes a unique case of multiple myxoid cellular neurothekeomas arising in a 60 year old female with systemic lupus erythematosus. Two papular lesions were identified involving the skin inferior to the umbilicus and the left inguinal crease. Both lesions were histopathologically similar, forming a nodular mass composed of epithelioid cells in a prominent myxoid stroma. By immunohistochemistry the lesional cells expressed NKI/C3, microphthalmia transcription factor (MiTF), and CD68, with focal staining for PGP9.5, factor XIIIa, and CD10 also observed. The tumors were negative for S‐100, SOX‐10, epithelial membrane antigen (EMA), desmin, smooth muscle actin (SMA), glial fibrillary acid protein (GFAP), and CD34. The present case confirms that cellular neurothekeoma can present clinically as multiple lesions and can have a predominantly myxoid appearance, potentially mimicking other cutaneous myxoid lesions. This article is protected by copyright. All rights reserved.

Ossifying plexiform tumor is an exceedingly rare cutaneous neoplasm with distinctive histologic features. The typical microscopic appearance is that of a well-circumscribed dermal lesion composed of spindled and epithelioid cells in a myxoid appearing matrix with a plexiform architecture associated with areas of ossification. The present report details the clinicopathologic features of an ossifying plexiform tumor involving the lower extremity of a 69-year-old man. The cutaneous lesion exhibited characteristic morphologic features of this entity. By immunohistochemistry, the tumor was negative for most markers assessed, but notably exhibited diffuse positivity for SATB2. No lesional recurrence was observed. The present case serves to expand on the limited existing knowledge regarding the clinicopathologic features of this uncommon tumor. The histogenesis of ossifying plexiform tumor remains unclear; however, the demonstration of SATB2 expression in this case suggests osteoblastic differentiation.

Schwannomas commonly occur in the head and neck but infrequently involve the oral cavity and rarely affect the tongue. The clinical and pathologic features of 19 cases of schwannoma arising in the tongue were analyzed. There were 13 males and 6 females ranging in age from 12 to 82 years (mean 34 years; median 29 years). The majority of tumors presented as an asymptomatic mass localized to the anterior two-thirds of the tongue. Histologically, 18 schwannomas exhibited characteristic Antoni A and B areas with the former pattern predominating. One tumor was composed exclusively of cellular Antoni A tissue and was classified as a cellular schwannoma. Tumor encapsulation was variable with nearly half of the lesions lacking a well-defined fibrous capsule. All were strongly and diffusely positive for S-100 protein. No recurrences were observed on clinical follow-up. Schwannoma of the tongue, although rare, should be separated from other types of lingual nerve sheath proliferations and tumors.

Neurofibromas rarely occur within the oral cavity and infrequently involve the tongue. The majority of lingual neurofibromas arise in patients affected by neurofibromatosis type 1 (NF1). Neurofibromas of the tongue unassociated with this disorder are exceedingly uncommon. The clinical and pathologic features of 10 cases of sporadic lingual neurofibromas, unassociated with NF1, were evaluated. The patients included six females and four males ranging in age from 30 to 69 years (mean 59 years; median 63 years). An asymptomatic or slowly enlarging lingual mass was the most common clinical presentation. None of the patients were documented to have NF1. Histologically, the tumors were unencapsulated and situated beneath an intact squamous mucosa. The tumors are comprised of spindle cells with wavy nuclei within a collagenous to myxoid stroma. One tumor was characterized by a plexiform growth pattern. The lesional cells were positive for S-100 protein. Clinical follow up, available for all patients, showed no recurrences and no subsequent development of additional clinical manifestations of NF1. Lingual neurofibromas should be distinguished from other peripheral nerve sheath tumors that can affect this anatomic site. This series of cases confirms that sporadic neurofibromas of the tongue may be rarely encountered in patients having no other features of NF1.

Solitary fibrous tumors of the thyroid gland are exceptionally rare. In order to further characterize the clinical and pathologic features of solitary fibrous tumor arising at this anatomic site, three cases of thyroid gland solitary fibrous tumor were analyzed in conjunction with 35 cases compiled from the English literature. Thyroid gland solitary fibrous tumors showed an equal sex distribution with a mean age at presentation of 54.4 years (range, 28–88 years). The patients typically presented with an asymptomatic, slow growing neck mass. Microscopically, the tumors were characterized by cytologically bland spindle cells with patternless growth, hypocellular and hypercellular areas, variable amounts of collagen, and ectatic, branching blood vessels. Two previous reported tumors were considered to be histologically malignant on the basis of increased mitotic activity, profound pleomorphism and tumor necrosis. Immunohistochemically, the tumor cells are variably positive with CD34, bcl-2, and CD99. STAT6 immunohistochemistry, performed on the current cases, demonstrated a strong, diffuse nuclear expression in all tumors. Among 26 patients with available follow up data (mean 47.3 months), one developed local recurrence and distant metastasis. Solitary fibrous tumors occurring in the thyroid gland are uncommon, but can be reliably diagnosed based on the presence of characteristic morphologic features as well as immunohistochemical expression of STAT6 and CD34. The majority of thyroid gland solitary fibrous tumors have exhibited an indolent clinical course, however experience is limited. The rare potential for aggressive clinical behavior requires clinical surveillance.

Solitary fibrous tumors (SFTs) are well recognized in the head and neck region, but rarely arise in the sinonasal tract (SNT). Six primary SNT SFTs were identified in the files of Southern California Permanente Medical Group between 2006 and 2017. The patients included five males and one female ranging in age from 33 to 72 years (mean 52 years), most of whom presented clinically with nasal obstruction. Three tumors involved the nasal cavity alone, one involved the paranasal sinuses, and two involved both the nasal cavity and paranasal sinuses. Histologically, the tumors were characterized by a variably cellular proliferation of cytologically bland spindle cells within a collagenous stroma with prominent interspersed branching vessels. Mitotic activity was low (range 0–2 per 10 high power fields) and there was no evidence of pleomorphism or tumor necrosis. Surface ulceration was noted. By immunohistochemistry, the lesional cells were positive for CD34, STAT6 and bcl-2. Clinical follow up information was available for all patients (range 32–102 months; mean 72 months). There were no recurrences or metastases and all were alive with no evidence of disease at last follow-up. SFTs rarely affect the SNT, but should be considered in the differential diagnosis of SNT mesenchymal lesions. Immunohistochemical expression of STAT6 can aid in diagnosis and separation of SFT from other spindle cell lesions occurring at this anatomic site. In combination with cases reported in the literature, primary SNT SFT behave in an indolent manner with conservative treatment.