Alexander Maly

Deep Infection by Trichophyton rubrum in an Immunocompromised Patient

ABSTRACT Dermatophytes are common pathogens of skin but rarely cause invasive disease. We present a case of deep infection by Trichophyton rubrum in an immunocompromised patient. T. rubrum was identified by morphological characteristics and confirmed by PCR. Invasiveness was apparent by histopathology and immunohistochemistry. The patient was treated successfully with itraconazole.

Primitive neuroectodermal tumor of the kidney. Report of a case initially diagnosed by fine needle aspiration cytology.

BACKGROUND Primitive neuroectodermal tumor (PNET) is a malignant small round cell tumor that exhibits neuroepithelial differentiation, most often presenting as a bone or soft tissue mass in the trunk or axial skeleton in adolescents and young adults. Isolated cases of PNET have been observed at visceral sites, such as the ovary, testis, uterus, bladder and pancreas. We present a case of PNET in the kidney initially diagnosed by fine needle aspiration (FNA). CASE A 21-year-old woman presented with microhematuria. Urine cytology was negative for malignant cells. Physical examination was without abnormal findings. Computerized tomography revealed a partially cystic tumor in the left kidney. FNA showed monotonous-appearing small round tumor cells with occasional rosette formation. The differential diagnoses include other primitive small round cell tumors. The tumor cells were immunoreactive for neuron specific enolase and O13 (CD99). A cytologic diagnosis of PNET was suggested and subsequently confirmed on histopathology. CONCLUSION To our knowledge, this is the first description of PNET of the kidney initially diagnosed by FNA. This nerve tumor must be included in the differential diagnosis of small cell malignant tumors of the kidney and adjacent organs.

Fine needle aspiration biopsy of Intraparotid schwannoma: A case report

BACKGROUND Intraparotid schwannoma of the salivary gland is a rare entity. Review of the literature revealed one previous report describing its cytologic features. CASE A 22-year-old man had a slowly growing, painless mass in the left parotid gland. Fine needle aspiration biopsy, performed prior to surgical excision, showed several tissue fragments consisting of uniform, spindle-shaped neoplastic cells with cigar-shaped nuclei and scant, ill-defined cytoplasm. Some of the neoplastic cells were clustered in typical arrangements of Verocay bodies. In addition, lymphocytes and foamy histiocytes were found. A diagnosis of schwannoma was made. Pathologic evaluation of the resected parotid mass supported the diagnosis. CONCLUSION The diagnosis of intraparotid schwannoma can be made by examining cytologic material containing the characteristic Verocay bodies. The correct cytologic diagnosis of this entity helps to rule out morphologically similar primary salivary gland neoplasms and thereby permits the appropriate surgical procedure to ensue.

H syndrome: recently defined genodermatosis with distinct histologic features. A morphological, histochemical, immunohistochemical, and ultrastructural study of 10 cases.

This study analyzes the histopathological findings in H syndrome, a recently recognized autosomal recessive genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin in well-defined anatomical areas accompanied by various systemic manifestations. So far, descriptions of the histopathological skin changes in this disorder, as reported in a few small case series, were inconsistent, leading to diverse clinical interpretations. In an attempt to define standardized, diagnostic, morphological criteria that will distinguish this disorder from other fibrosing conditions, we studied skin biopsies from 10 patients with H syndrome. The characteristic morphology included widespread fibrosis (moderate in dermis and severe in subcutis); striking mononuclear infiltrates consisting mainly of monocyte-derived cells (small CD68+ histiocytes and CD34+ and FXIIIa+ dendrocytes) and plasma cells; and thickened, fragmented, and partially calcified elastic fibers, admixed with well-formed psammoma bodies, a previously unrecognized feature in nonneoplastic skin and subcutaneous conditions. In addition, the ultrastructure of CD68+ small histiocytes exhibited distended endoplasmic reticulum and scarcity of lysosomes, features typical for fibroblasts but unusual for histiocytes. These unusual findings in the histiocytes pose a question as to their possible role in the fibrotic cascade in this disorder. We conclude that the above findings are essential for the diagnosis of H syndrome and that incisional biopsies are mandatory for recognition of the full spectrum of histopathological findings.

Eyelid Pilomatrixoma : A Description of 16 cases and a Review of the Literature

Pilomatrixoma is an uncommon benign neoplasm that originates from the matrix of the hair root. It occurs more frequently in the head and neck region of children and adolescents, often involving the eyelid or eyebrow. Pilomatrixoma is often misdiagnosed clinically and the correct diagnosis can be established only after excision and histological examination. Pathologic diagnosis of pilomatrixoma is based on the finding of large masses of shadow cells, combined with basophilic cells, inflammation, foreign body giant cells, calcification, and ossification. We report 16 cases of eyelid pilomatrixoma that were treated in our department, and review the relevant literature.

Radiation-Induced Loss of Salivary Gland Function Is Driven by Cellular Senescence and Prevented by IL6 Modulation.

Head and neck cancer patients treated by radiation commonly suffer from a devastating side effect known as dry-mouth syndrome, which results from the irreversible loss of salivary gland function via mechanisms that are not completely understood. In this study, we used a mouse model of radiation-induced salivary hypofunction to investigate the outcomes of DNA damage in the head and neck region. We demonstrate that the loss of salivary function was closely accompanied by cellular senescence, as evidenced by a persistent DNA damage response (γH2AX and 53BP1) and the expression of senescence-associated markers (SA-βgal, p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6). Notably, profound apoptosis or necrosis was not observed in irradiated regions. Signs of cellular senescence were also apparent in irradiated salivary glands surgically resected from human patients who underwent radiotherapy. Importantly, using IL6 knockout mice, we found that sustained expression of IL6 in the salivary gland long after initiation of radiation-induced DNA damage was required for both senescence and hypofunction. Additionally, we demonstrate that IL6 pretreatment prevented both senescence and salivary gland hypofunction via a mechanism involving enhanced DNA damage repair. Collectively, these results indicate that cellular senescence is a fundamental mechanism driving radiation-induced damage in the salivary gland and suggest that IL6 pretreatment may represent a promising therapeutic strategy to preserve salivary gland function in head and neck cancer patients undergoing radiotherapy.

The coexistence of Sweet's syndrome and Still's disease--is it merely a coincidence?

Sweets syndrome has a wide range of clinical manifestations. It may appear as a solitary cutaneous disorder but often it is associated with systemic signs and symptoms. This disorder might be idiopathic but it often is paraneoplastic or associated with medications or autoimmune diseases. In its systemic manifestation Sweets disease resembles adult-onset Stills disease in many aspects. We present a case of a young man in whom Sweets syndrome and Stills disease developed. Although the diagnosis of adult-onset Stills disease is made by exclusion, he fulfilled all the criteria of both conditions. Considering the clinical similarities of these diseases, it may be presumed that similar patients may have been overlooked in the past.

Histological criteria for grading of atypia in melanocytic conjunctival lesions

Aims: To develop a standardised protocol for grading atypia in melanocytic conjunctival lesions (MCL), mainly primary acquired melanosis (PAM) and inflamed juvenile conjunctival naevi (IJCN) and to establish prognostic parameters for progression to malignant melanoma (MM). Methods: A retrospective non‐randomised study of 304 patients with MCL was conducted. Histological slides of MCL diagnosed as conjunctival naevus (CN; 222 cases), PAM (42 cases), and IJCN (40 cases) were reviewed. A scoring method of atypia was developed according to the following histological parameters: nest cohesion, melanocytic hyperplasia, nuclear features, and pagetoid spread. Lesions were scored according to the number of criteria as mild (1–2), moderate (3–4) and severe (5–8). Results: Nineteen PAM lesions showed mild (n = 8), moderate (n = 4), and severe (n = 7) atypia. The remaining PAM lesions were without atypia. IJCN cases showed architectural disorder only. Neither architectural disorder nor cytological atypia were found in the CN. There were no recurrences in the IJCN and PAM lesions without and with mild atypia, while two PAM with moderate and two with severe atypia recurred. Three cases (two of which had a history of recurrent PAM with severe atypia) progressed to MM. The criteria for evaluation of atypia were found to be significantly associated with the clinical outcome (p < 0.0001). Conclusion: The standardised histological scoring protocol of MCL is reliable, and may reduce the risk of confusing a benign MCL, such as IJCN, with one that is potentially preneoplastic. It may also prove useful in predicting which PAM lesions will progress to MM.

Noninvasive visualization of intraepidermal and subepidermal blisters in vesiculobullous skin disorders by in vivo reflectance confocal microscopy

IntroductionBullous dermatoses are characterized by skin blisteringresulting from local injury with breakdown of tissue integrityand fluid accumulation within specific layers of the skin.These disorders are traditionally classified into subcorneal,suprabasal, and subepidermal blistering by the specificlocationofthesplitintheepidermis[1, 2]. Of special interestis the group of autoimmune blistering diseases that comprisea wide spectrum of clinical presentations and are mediatedby pathogenic antibodies targeting specific adhesion mole-cules responsible for cutaneous homeostasis and integrity[3]. Diagnosis is based on the clinical picture, histology,direct and indirect immunofluorescence, immunoblotting,immunoprecipitation and immunoelectron microscopy [4, 5].Though crucial for accurate diagnosis and for selection ofspecific therapy, these techniques are cumbersome, time-consuming and unlikely to be widely available, leavingblister level determination by classical histology a keydiagnostic procedure in intraepidermal and subepidermalblistering diseases.Reflectance confocal microscopy (RCM) is a novel,noninvasive imaging technique which permits real timevisualization of cellular components in the skin at aresolution compatible with that of conventional histology[6]. RCM detects single back-scattered photons directlyfrom illuminated living tissue without prior preparation ofthe examined skin. A small pinhole in the front of thedetector allows imaging at high resolution. Contrast inconfocal images is provided by the differences in refractiveindex among the cellular organelles and structures. Melaninacts as a contrast agent in pigmented epithelia [7]. With thecurrent technology, in vivo RCM imaging is limited to adepth of approximately 300 µm which includes the entireepidermis, the papillary dermis and the upper reticulardermis. It is of interest that the depth of RCM imaging canbe increased by using the so-called “optical clearing”approach, and experimental studies utilizing gold nano-particles and osmotically active immersion liquids asoptical clearance agents have indeed increased the imagingdepth of RCM up to three times [8–11]. However, theseexperimental approaches have not yet been incorporatedinto clinically useful RCM technology. Since contrast in theimages is primarily provided by melanin, RCM has mainlybeen useful in the diagnosis of pigmented cutaneous tumorssuch as melanoma and nevi [12], and nonmelanoma skincancers [13, 14]. The use of RCM has also been reported inthe diagnosis of a variety of inflammatory skin disordersincluding psoriasis [15], contact dermatitis [16, 17], vitiligo[18], cutaneous lupus erythematosus [19, 20], folliculitis[21], and photoaging [22]. In a recent paper, Angelova-Fischer et al. [23] demonstrated the use of RCM in thediagnosis of subcorneal blisters in two patients withpemphigus foliaceus in which the dark nonrefractive blistercavity was readily visible against a background of bright,

Nested (Ossifying) Stromal Epithelial Tumor of the Liver: Case Report

Nested stromal-epithelial tumor (NSET) of the liver is an extremely rare primary hepatic tumor with uncertain malignant potential. To date, only 11 cases have been described. We describe the case of a 2 1/2-year-old girl with an incidental liver mass. The mass was discovered on follow-up abdominal imaging for asymptomatic hydronephrosis diagnosed on antenatal ultrasound. Needle biopsy showed a mixed stromal and epithelial process in a nested pattern, with foci of ossification and no significant pleomorphism or necrosis. The nest cells stained with WT-1, cytokeratin 18, and CD56. Ossifying stromal epithelial tumor of the liver was strongly suspected. The findings were confirmed in the subsequent partial hepatectomy specimen. To our knowledge, this is the 12th case of NSET in the English-language literature and the 3rd case of NSET associated with genitourinary system abnormalities. Possible associations with dysregulated WT-1 expression are discussed.