Disseminated and penile mpox with histopathologic correlation: Two separate case reports.

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.

PRAME immunohistochemistry of spitzoid neoplasms.

BACKGROUND: Spitzoid melanocytic neoplasms are well known to be diagnostically challenging. Immunohistochemistry (IHC) and molecular approaches have been used as ancillary diagnostic tests. Herein, we investigate the use of PRAME IHC for the assessment of spitzoid melanocytic neoplasms. METHODS: Ten 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, three cases had positive sentinel lymph nodes, which showed PRAME score of 2, 4, and 4 in the metastatic deposits. CONCLUSIONS: Previous reports revealed PRAME IHC as useful tool 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.

Multiple myxoid cellular neurothekeomas in a patient with systemic lupus erythematosus.

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, desmin, smooth muscle actin, glial fibrillary acid protein, 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.

Ossifying Plexiform Tumor: A Case Report.

ABSTRACT: 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.

Cutaneous Smooth Muscle Tumors: A Review.

Smooth muscle tumors occur infrequently in the skin. They consist of a diverse group of lesions representing hamartomas as well as benign and malignant neoplasms. They may arise from arrector pili muscle, specialized smooth muscle of the genitalia, or vascular smooth muscle. Although rare, accurate diagnosis and classification of cutaneous smooth muscle proliferations is important as they can exhibit a range of clinical behavior and may be associated with underlying syndromes. This review summarizes the clinicopathologic spectrum of smooth muscle tumors involving the skin.

Association of reactive oxygen species levels and radioresistance in cancer stem cells.

The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.

Absence of Differential Cyclin D1 Immunohistochemical Protein Expression in Nevi and Melanoma Evaluated by Digital Image Analysis.

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.

Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology.

Patients with locally advanced/inflammatory breast cancer (LABC/IBC) face a high likelyhood of recurrence and prognosis for relapsed, or de novo stage IV metastatic breast cancer (MBC) remains poor. Estrogen (ER) and HER2 receptor expression on primary or MBC allow targeted therapies, but an estimated 10-18% of tumors do not exhibit these biomarkers and survival in these cases is even poorer. Variations in discordance rates for the expression of ER and HER2 receptors have been observed between primary and metastatic tumors and such discordances may lead to suboptimal treatment. Circulating tumor cells (CTCs) are considered the seeds of residual disease and distant metastases and their characterization could help guide treatment selection. To explore this possibility, we used multiple biomarker assessment of CTCs in comparison to primary and metastatic tumor sites. Thirty-six patients with LABC/IBC, or stage IV MBC were evaluated. Blood samples were procured prior to initiating or changing therapy. CTCs were identified based on presence of cytokeratin and nucleus staining, and the absence of CD45. A multimarker assay was developed to simultaneously quantify expression of HER2, ER, and ERCC1, a DNA excision repair protein. Novel fiber-optic array scanning technology (FAST) was used for sensitive location of CTCs. CTCs were detected in 82% of MBC and 62% LABC/IBC cases. Multiplex marker expression was successfully carried out in samples from18 patients with MBC and in 8 patients with LABC/IBC that contained CTCs. In MBC, we detected actionable discordance rates of 40 and 23%, respectively for ER and HER2 where a biomarker was negative in the primary or metastatic tumor and positive in the CTCs. In LABC/IBC, actionable discordances were 60 and 20% for ER and HER2, respectively. Pilot trials evaluating the effectiveness of treatment selections based on actionable discordances between biomarker expression patterns on CTCs and primary or metastatic tumor sites may allow for a prospective assessment of CTC-based individualized targeted therapies.

Mixed cortical adenoma and composite pheochromocytoma-ganglioneuroma: an unusual corticomedullary tumor of the adrenal gland.

Adrenal neoplasms composed of more than one cell type and demonstrating a mixed histologic appearance are exceedingly rare. We report the clinical and pathologic features of a morphologically distinctive tumor of the adrenal gland composed of cortical, chromaffin, and neural cells. Histologically, the tumor consisted of intermixed areas of proliferating cortical cells resembling adrenal cortical adenoma, neoplastic chromaffin cells consistent with pheochromocytoma, and a ganglioneuromatous stroma. The presence of the cortical, medullary, and neural components within the tumor was confirmed by immunohistochemical studies. The present case serves to broaden the morphologic spectrum of mixed tumors that may be encountered in the adrenal gland.

Oncocytoma of the kidney with prominent intracytoplasmic lumina.

Oncocytoma is a histologically distinctive neoplasm of the kidney, with a well-recognized cytoarchitectural appearance. On occasion, however, renal oncocytomas are known to exhibit unusual morphologic features that may pose diagnostic difficulties. We present the clinical and pathologic details of an oncocytoma of the kidney with an unusual histologic appearance imparted by the presence of large numbers of prominent intracytoplasmic lumens. Morphologically, the neoplasm was composed of uniform polygonal cells with copious amounts of granular, eosinophilic cytoplasm, round nuclei, and prominent nucleoli, exhibiting an organoid pattern of growth. Intracytoplasmic lumina of varying size were present throughout the tumor. There were no mitotic figures or areas of necrosis present. The diagnosis of oncocytoma was supported by immunohistochemical and ultrastructural studies. By electron microscopy, the intracytoplasmic lumens appeared as membrane bound spaces with associated microvilli. The presence of intracytoplasmic lumina in a significant proportion of cells is an uncommon feature of renal oncocytoma which can generate problems in diagnosis. Awareness of this phenomenon should allow for improved recognition of oncocytomas exhibiting this type of unusual morphology.

Papillary carcinoma of the breast: an overview.

Papillary carcinoma of the breast represents approximately 0.5% of all newly diagnosed cases of breast cancer. The prevalence of both invasive and in situ papillary carcinoma seems to be greater in older postmenopausal women and, in relative terms, in males. Histologic features of the tumor include cellular proliferations surrounding fibrovascular cores, with or without invasion. In this review, characteristics of both in situ and invasive disease are outlined. Immunohistochemical analyses of papillary carcinoma suggest the utility of markers such as smooth muscle myosin heavy chain, calponin, p63, and high molecular weight keratins, which can characterize the myoepithelial cell layer. With respect to radiographic evaluation of papillary carcinoma, ultrasonography is the most extensively studied imaging modality, though magnetic resonance mammography has potential utility. Available data suggest improved outcome for papillary carcinoma as compared to invasive ductal carcinoma. Treatment-related information for patients with papillary carcinoma is limited, and patterns noted in available series suggest a variable approach to this disease. The scarcity of information underscores the need for further treatment- and outcome-related studies in papillary carcinoma of the breast.

Sporadic Neurofibroma of the Tongue Unassociated with Neurofibromatosis Type I: A Clinicopathologic Study of Ten Cases.

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.

Tongue Schwannoma: A Clinicopathologic Study of 19 Cases.

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.

Assessment of low prostate weight as a determinant of a higher positive margin rate after laparoscopic radical prostatectomy: a prospective pathologic study of 1,500 cases.

BACKGROUND: The assessment of prostate weight as a determinant of a high prostate margin rate after laparoscopic radical prostatectomy has not been studied. METHODS: Prospective pathologic findings of 1,500 patients who underwent laparoscopic radical prostatectomy (LRP, 399 cases) and da Vinci prostatectomy (DVP, 1,101 cases) between December 2000 to June 2006 at City of Hope National Medical Center were evaluated. Gleason score, pathologic stage, the presence or absence of positive margins, extraprostatic tumor extension, and seminal vesicle involvement by tumor were recorded in all patients. Preoperational serum prostate specific antigen (PSA) levels were recorded in all but 13 cases. These parameters were then correlated with prostate weight. RESULTS: Of 1,500 patients, 345 had one or more positive margins (23%). Patients with low median prostate weight (49 g) had a significantly higher positive margin rate (p < 0.0001) and incidence of extraprostatic extension by tumor (p = 0.04), and were 1.523 times more likely to have positive margins [95% confidence interval (CI) 1.167-1.985]. CONCLUSION: We conclude that low prostate weight may be a determinant of a higher recurrence rate and more aggressive disease.

Keratin expression in endocrine organs and their neoplasms.

Keratins are intermediate filaments that provide mechanical support and fulfill a variety of additional functions in epithelial cells. Keratins show outstanding degree of molecular diversity. In humans, 54 functional keratin genes exist. Twenty common types of keratins are expressed in highly specific patterns related to epithelial type and stage of cellular differentiation. In general, keratins are classified as high-molecular-weight keratins (expressed in normal stratified epithelium and tumors derived from it) and low-molecular-weight keratins (expressed in normal simple epithelium and tumors derived from it). Histologically, endocrine organs belong to simple epithelium; thus, endocrine tissues usually express low-molecular-weight keratins. When an endocrine organ undergoes malignant transformation, its keratin profile usually remains constant. However, keratin expression in endocrine organs and endocrine tumors is much more complicated because of their diversified histogenesis. In this review article, we will first briefly review the molecular biology and protein chemistry of the keratins. We will then review the expression patterns of keratins in normal endocrine tissue and endocrine neoplasms.

Infection due to Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) presenting as ischemic colitis.

Infections due to Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) are often mild and self-limiting, but more severe cases can develop into hemolytic uremic syndrome (HUS) and hemorrhagic colitis. This case report documents a sporadic case of ischemic colitis likely triggered by EHEC but without manifestations of hemolytic uremic syndrome. From our literature review, we identified only one other case of an EHEC infection presenting as ischemic colitis in the absence of HUS. To our knowledge, this is the first case presentation of EHEC-induced ischemic colitis which did not lead to significant morbidity.

Thyroid Gland Solitary Fibrous Tumor: Report of 3 Cases and a Comprehensive Review of the Literature.

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.

Immunohistochemical expression of Langerin in Langerhans cell histiocytosis and non-Langerhans cell histiocytic disorders.

Langerin is a type II transmembrane C-type lectin associated with the formation of Birbeck granules in Langerhans cells. Langerin is a highly selective marker for Langerhans cells and the lesional cells of Langerhans cell histiocytosis. Although Langerin protein expression in Langerhans cell histiocytosis has been previously documented, the specificity of Langerin expression as determined by immunohistochemistry in the context of other histiocytic disorders has not been well established. In the present study, Langerin immunoreactivity was examined in a series of histiocytic disorders of monocyte/macrophage and dendritic cell derivation to assess the specificity and utility of Langerin as a diagnostic marker for Langerhans cell histiocytosis. Immunohistochemical expression of CD1a was also evaluated for comparison. Seventeen cases of Langerhans cell histiocytosis and 64 cases of non-Langerhans cell histiocytic disorders were examined. Langerin and CD1a were uniformly expressed in all cases of Langerhans cell histiocytosis, with the exception of one case that was positive for Langerin and negative for CD1a. Among the non-Langerhans cell histiocytic disorders evaluated, focal Langerin immunoreactivity was observed only in 2 of 10 cases of histiocytic sarcoma. All non-Langerhans cell histiocytic disorders showed no expression of CD1a. Langerin expression seems to be a highly sensitive and relatively specific marker of Langerhans cell histiocytosis. Immunohistochemical evaluation of Langerin expression may have utility in substantiating a diagnosis of Langerhans cell histiocytosis and separating this disorder from other non-Langerhans cell histiocytic proliferations.

Distinction of hepatocellular carcinoma from benign hepatic mimickers using Glypican-3 and CD34 immunohistochemistry.

Distinguishing a well-differentiated hepatocellular carcinoma (HCC) from normal and cirrhotic liver tissue or benign liver nodules, such as hepatic adenoma (HA) and focal nodular hyperplasia (FNH), may be very difficult in some cases, particularly in small needle core biopsies. We studied the expression of Glypican-3 (GPC3) and CD34 in 107 cases of HCC, 19 cases of HA, and 16 cases of focal nodular hyperplasia (FNH). In addition, we studied GPC3 expression in 225 cases of nonhepatic human tumors with epithelial differentiation. Ninety-four of 107 cases (88%) of HCC showed focal or diffuse cytoplasmic GPC3 staining, whereas all HA and FNH cases were GPC3-negative, and only 7 of 225 cases (3%) of nonhepatic tumors with epithelial differentiation expressed GPC3. The sensitivity and specificity of GPC3 for HCC was 88% and 97%, respectively. There were three CD34 staining patterns observed in hepatic tissue: negative, incomplete positive, and complete positive. In negative staining pattern, only blood vessels in portal triads or rare sinusoidal spaces immediately adjacent to portal tracts were positive. The negative staining pattern was seen in normal or cirrhotic liver tissue only. The complete CD34 staining pattern showed virtually all sinusoidal spaces with CD34-positive staining throughout the lesion. The complete CD34 staining pattern was seen in virtually all cases of HCC and in only some cases of HA and FNH. The incomplete CD34 staining pattern was characterized by either CD34 positivity in virtually all sinusoidal spaces in some but not all nodules or CD34 positivity in the peripheral sinusoidal spaces adjacent to portal triads. The incomplete CD34 staining pattern was seen in rare cases of HCC and in most cases of HA and FNH. We conclude that GPC3 is a very specific marker not only for differentiating HCC from nonhepatic tumors with epithelial differentiation, but also for differentiating HCC from HA and FNH. GPC3 immunoreactivity, in combination with a complete CD34 immunostaining pattern, greatly facilitates the accuracy of distinguishing between malignant hepatic lesions and benign mimickers.

Sinonasal Tract Solitary Fibrous Tumor: A Clinicopathologic Study of Six Cases with a Comprehensive Review of the Literature.

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.