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Biomedical subjects

S Regauer

Publications and source records attributed to S Regauer.

At least 37 records · Page 2Linked to original sources

Evidence of fetal microchimerism in Hashimoto's thyroiditis.

Fetal microchimerism, the engraftment of fetal progenitor cells into maternal tissues, has been implicated in the etiology of autoimmune diseases. We used PCR analysis to determine whether microchimerism occurred in the thyroid glands of female patients suffering from Hashimoto's disease and thus may be involved in its etiology. PCR amplification was performed from thyroid gland specimens using primers unique to a Y-chromosomal sequence (SRY gene) and primers for a sequence that is Y/X-chromosomal homologous except for a 6-bp deletion in the X-chromosomal sequence (amelogenin). Microchimerism was detected in 8 of 17 Hashimoto patients, but in only 1 of 25 controls (nodular goiters). Both groups were of similar age and had comparable numbers of pregnancies and numbers of sons. All individuals with microchimerism had given birth to at least 1 son. Our results show that microchimerism is significantly more common in Hashimoto patients than in patients suffering from nodular goiter. We therefore suggest that microchimerism might play a role in the development of Hashimoto's disease, although we cannot completely eliminate the hypothesis that microchimerism is just an "innocent bystander" in a process triggered by other mechanisms.

Adult↗

Trichoblastic carcinoma ("malignant trichoblastoma") with lymphatic and hematogenous metastases.

We report an aggressively behaving malignant trichogenic tumor arising in a trichoblastoma (TB) with widespread lymphatic and hematogenous metastases in a 55-year-old man with a concomitant B-cell chronic lymphocytic leukemia. The primary tumor had been present and unchanged for as long as 40 years before excision. Typical trichogenic TB with dystrophic calcification and even ossification was still present peripheral to the malignant transformation. The malignant neoplasm consisted of basaloid cells, spindle cells arranged in fascicles and densely packed rounded nests or "cell balls." The metastases consisted of immature basaloid cells and cell balls, and the recurrences became successively more undifferentiated. The residual TB reacted with antibodies to cytokeratin (CK) 6, 8, 14, and 17 and focally to S-100; the malignant primary tumor reacted uniformly with antibodies to vimentin and only focally with antibodies to CK and S-100. The metastatic tumor had lost epidermal CK expression but maintained expression of S-100 in paraffin-embedded tissues. Trichoblastic differentiation was confirmed in frozen tissues with antibodies to hair keratins. No expression of p53 or bcl-2 was identified, but p-glycoprotein (MDR-1 gene related) was expressed by primary and metastatic tumor cells. We believe that this neoplasm is best classified as a trichoblastic carcinoma arising in a TB in association with a B-cell chronic lymphocytic leukemia. This case illustrates that TBs have the potential for malignant transformation and aggressive behavior.

Biomarkers↗

CK7 expression in carcinomas of the Waldeyer's ring area.

Primary carcinomas of the Waldeyer's ring area are typically nonkeratinizing squamous cell carcinomas (SCC). Their cervical lymph node metastases are not uncommonly cystic and filled with necrotic tumor cells. Some cysts, however, contain clear fluid. During the investigation of SCC producing "fluid-filled" cystic metastases, we evaluated hematoxylin and eosin (H&E) sections of 90 primary SCC for their site of origin. We analyzed the cytokeratin (CK) profile of primary and metastatic carcinoma with special focus on the expression of CK7, a putative marker for ductal differentiation. CK7 was expressed in submucosal minor salivary gland acini and ducts, but not in the squamous surface epithelium of the Waldeyer's ring. CK7 was expressed in 11 primary SCC (8 base of tongue/3 palatine tonsil). The CK7-positive SCC were deep-seated, arose from large excretory ducts of submucosal minor salivary glands, and showed only insignificant surface involvement. They were characterized by a solid infiltrative growth pattern of basaloid cells with focal ductal differentiation. Salivary ducts adjacent to the carcinoma showed extensive intraductal hyperplasia and metaplasia. All CK7-positive carcinomas produced CK7-positive cystic nodal metastases, most of which contained paucicellular fluid. No solid CK7-positive nodal metastases were identified. In summary, a subset of carcinomas occurring in the Waldeyer's ring area appear to arise from large excretory ducts of submucosal minor salivary glands with only limited surface involvement, express CK7, and produce CK7-positive cystic "fluid-filled" nodal metastases. The histomorphology and immunophenotype suggest that these carcinomas represent basaloid SCC arising from excretory ducts of the submucosal minor salivary glands.

Biomarkers, Tumor↗

Expression of oestrogen and progesterone receptors in low-grade endometrial stromal sarcomas.

We analysed oestrogen receptor (ER) and progesterone receptor (PR) expression in a retrospective series of 21 low-grade endometrial stromal sarcomas (LGSSs). Archival formalin-fixed and paraffin-embedded material was analysed by immunohistochemistry. ER and PR were measured with monoclonal antibodies and the peroxidase-antiperoxidase method and a score was calculated as for breast carcinoma based on both the percentage of positive tumour cell nuclei and the staining intensity. ER were seen in 15 (71%) and PR in 20 (95%) of tumours respectively. ER expression was scored as high in three (14%), moderate in four (19%), and low in eight (38%) tumours. Six (29%) tumours did not stain for ER and all of these were positive for PR. PR expression was scored as high in eight (38%), moderate in ten (47%) and weak in two (10%) LGSSs. Only one (5%) LGSS did not stain for PR (this tumour was positive for ER). ER and PR expression in LGSS is heterogeneous. This may have implications for hormone therapy in the management of these tumours. These results suggest that ER and PR should be routinely quantified in LGSSs by immunohistochemical methods.

Adult↗

Healing process after alveolar ridge distraction in sheep.

OBJECTIVE: Mandibular augmentation by distraction of the alveolar ridge has been in use for several years. Since 1996, a distraction device that remains in the alveolar ridge after distraction has been used by the Department of Oral and Maxillofacial Surgery of Graz University. The distraction device is transformed into a dental implant after the end of the distraction process and can later be used for prosthetic purposes. We aimed to show the application of the device in this animal experiment and to follow the osseous healing process. STUDY DESIGN: Two distraction implants were inserted into the mandibles of 8 sheep. Distraction of 0.5 mm per day was carried out for 8 days. Two sheep were killed 1, 2, 3, and 6 months after distraction, and the dissected mandibles were examined clinically, radiologically, and histologically. RESULTS: After the first month of distraction, only slight radiopacity of the distraction gap was found. This increased steadily up to the third month after distraction. The boundary between the distraction fragments and the gap disappeared gradually. Six months after distraction, a homogeneous fine-meshed spongiosa structure was found in the area of distraction. Histologic examination showed desmoid ossification in the distraction gap and a continued increase in osteoid. After 6 months, mature bone was found. Only in the center was the rebuilding process not complete. Six months after distraction, osseointegration of the implants was shown in the region of the screw thread and distraction cylinder. CONCLUSIONS: The healing process corresponded to that found in long bones, but showed only desmal ossification. Osseous integration of the distraction implants was found 6 months after distraction, although the implants were stable 3 months after distraction.

Alveolar Ridge Augmentation↗

Nasopharyngeal angiofibroma: true neoplasm or vascular malformation?

Nasopharyngeal angiofibromas (NA) are rare tumor-like lesions characterized by architecturally irregular vessels set in a fibrous stroma. The unique morphology, the strong predilection for male adolescents, and the uncertainty about its etiology contributes to significant confusion regarding the classification of NA, which still has not been solved today. Based on immunohistochemical and electron microscopic examinations, we demonstrate in detail the various unusual vascular architectural features of NA. They represent discontinuous vascular basal laminae, focal lack of pericytes, and pronounced irregularity of the smooth muscle layers. In thick smooth muscle layers and pads, the orientation of muscle cells is frequently disturbed, and the individual cells differ in size and shape. Occasionally, the muscle layers disperse peripherally into individual cells, creating the impression of vessel-independent smooth muscle cells within the stroma. The summation of all morphological irregularities demonstrated in this paper allows the conclusion that NA represent vascular malformations.

Actins↗

CD44 expression in sinonasal melanomas: is loss of isoform expression associated with advanced tumour stage?

The expression of the adhesion molecule CD44 was examined in 14 primary sinonasal melanomas (SMs), aggressive neoplasms with short survival times, as CD44 overexpression has been linked to poor survival in human cancers. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections with CD44 isoform-specific monoclonal antibodies to the CD44 standard (s) and variant isoforms (v) v5 and v6. CD44s, v5, and v6 were strongly expressed in a membranous pattern in SM in situ, early invasive SM, and in uninvolved respiratory/squamous epithelium. In invasive SM, membranous CD44s expression was identified in a large proportion of melanoma cells. Membranous staining of CD44v5 and v6 was lost in invasive SM, independently of the histological subtype. Diffuse cytoplasmic staining was observed focally in invasive SM and loss of cytoplasmic expression of CD44v6 and v5 was associated with advanced tumour stage in the linear-by-linear association test (p = 0.042 and 0.066, respectively). CD44s may not be important for malignant transformation, as it is expressed in both benign and malignant melanocytes. Loss of membranous CD44 isoform expression in widely invasive SM suggests that loss of cellular adhesion facilitates matrix and vascular infiltration and dissemination of sinonasal melanoma cells.

Adult↗

Cystic lymph node metastases of squamous cell carcinoma of Waldeyer's ring origin.

We analysed in a retrospective study the frequency of cystic lymph node (LN) metastases in neck dissection specimens of 123 patients with primary squamous cell carcinoma (SCC) arising in the palatine tonsils (62 M/14 F), the base of the tongue (38 M/5 F) and the nasopharynx (2 M/2 F). Eighty-two per cent of patients had metastases (64 tonsillar SCC, 33 base of tongue SCC and all four nasopharynx SCC) in 368 LN of a total 2298 sampled LN. Thirty-nine per cent of patients had exclusively solid metastases and 37% of patients had exclusively cystic metastases. A total of 62 patients had some signs of cyst formation in one or more metastatically affected LN (27 with only histological evidence of cyst formation with luminal diameters < 5 mm, 35 with clinically detectable cyst with luminal diameter > 5 mm). Cystic metastases were more common in patients with SCC of the base of the tongue (P = 0.005), while solitary clinically evident cystic metastasis with lumina > 5 mm were found exclusively in tonsillar carcinoma (P = 0.024). In comparison with solid metastases, cyst formation was associated with N-categories (N2b and N3, P = 0.005) in SCC of the base of the tongue origin. No such association was observed for tonsillar SCC (P = 0.65). The primary mechanism of cyst formation was cystic degeneration.

Branchioma↗

Giant liposarcoma of the esophagus: radiological findings.

This case of an esophageal liposarcoma illustrates a polypoid lesion within the esophagus that extended from the left pyriform sinus to the distal esophagus above the gastric cardia. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) showed an inhomogenously-enhancing intraluminal mass, while video-fluoroscopy revealed that the mass was adherent to the esophageal wall and was associated with esophageal dilatation and diminished peristalsis. This ninth reported case of esophageal liposarcoma is the first described where preoperative radiologic studies and endoscopy showed broad fixation of the tumor to the esophageal wall.

Aged↗

Expression of CD34-antigen in nasopharyngeal angiofibromas.

Formalin-fixed, paraffin-embedded and frozen tissues of 24 patients with primary nasopharyngeal angiofibroma, of whom seven had recurrences, were studied immunohistochemically for the expression of CD34 antigen using two different antibodies (HPCA-1 and QBEND 10). In all cases, there was an exclusive staining of endothelial cells, while pericytes, smooth muscle cells and stromal fibroblasts were not reactive. The staining intensity, however, was more pronounced in small tumor vessels of capillary- and sinusoidal-type than in larger vessels, which were usually characterized by an irregular smooth muscle coat. This differential staining indicates an increased proliferative potential of the endothelium of the small vessel component of nasopharyngeal angiofibroma (neoangiogenesis) and an inhibitory influence of vascular smooth muscle cells on endothelial cell growth. Moreover, the positive immunoreaction of all endothelial cells for CD34 is indicative of the absence of lymphatic vessels, which confirms previous ultrastructural observations. No differences in the staining pattern were observed between primary versus recurrent tumors, formalin fixed, paraffin embedded versus snap-frozen acetone fixed material, or between both CD34 antibodies. Our findings indicate that nasopharyngeal angiofibroma is a vasoproliferative malformation.

Adolescent↗

Cultured human sole-derived keratinocyte grafts re-express site-specific differentiation after transplantation.

Cultured epithelial autografts (CEA) derived from sole skin were transplanted to full-thickness wounds excised to muscle fascia over a variety of diverse body sites in 12 pediatric patients treated for acute burns or giant congenital nevi. The skin regenerated from the grafts was biopsied from 7 days to 6 years after grafting. The resultant epidermal phenotype was analyzed histologically and by immunohistochemical localization of keratin 9 (K9) as objective evidence of sole-type site-specific differentiation. Expression of K9 was also verified by one-dimensional gel electrophoresis of epidermal cytoskeletal extracts and K9 immunoblot analysis. Grafts prepared from epidermis of axilla; groin or foreskin and transplanted to wounds of comparable depth in an identical manner in the same patients served as controls of postgrafting differentiation. Biopsies of sole skin from amputation specimens from patients of comparable age served as normal positive controls, and biopsies of nonsole skin from patients of comparable age served as normal negative controls. As early as 2 weeks postgrafting, the histologic appearance of sole-derived CEA differed substantively from that of axilla- or groin-derived CEA controls and displayed a phenotype characteristic of sole skin with a thick compact stratum corneum, a thick stratum granulosum, and a distinct stratum lucidum. In sole-derived grafts rete ridges regenerated within 2 months postgrafting, whereas nonsole-derived grafts required 4-6 months for rete ridge regeneration. Once acquired, the sole skin phenotype was maintained long-term by all sole-derived CEA. In vitro, sole-derived keratinocytes synthesized little, if any, K9. However, within 7 days after grafting, K9 synthesis by multiple suprabasal keratinocytes was seen within the epidermis regenerated from sole-derived CEA. Protein of K9 appeared progressively more diffuse throughout the suprabasal layers, attaining a confluent pattern of expression comparable to normal controls of sole skin by 6 to 12 months postgrafting, and the confluent pattern of suprabasal K9 synthesis was maintained long-term. The results demonstrate that site-specific differentiation is an intrinsic property of postnatal human keratinocytes and can be expressed and maintained in a permissive environment in the absence of dermal tissue.

Adolescent↗

Primary mucosal melanomas of the nasal cavity and paranasal sinuses. A clinicopathological analysis of 14 cases.

We present 14 patients with primary sinonasal melanomas (SM) identified from 1984-1997 in our archives (11/14 lateral nose, 1/14 nasal septum, 2/14 paranasal sinuses; 8M/6F, mean age 67.7 years, range 39-88 years). Survival was poor (median 9 months) with death related to extensive local disease and/or widespread hematogenous metastases. The following histological subtypes were identified in descending order: amelanotic small blue cell, pleomorphic, epithelioid, spindle cell and myxoid. High mitotic rate and vascular invasion, absence of tumor-infiltrating lymphocytes and regression were features shared by all SM. Negative staining of B- and T-cell markers, LCA, neuroendocrine markers such as NSE, chromogranin and synaptophysin, and CK-negativity excluded olfactory neuroblastoma, small cell undifferentiated carcinoma, and lymphoma. S-100 protein was expressed in all SM, but demonstrated variable staining intensity with areas of complete negativity. HMB45 was strongly and uniformly (>80%) expressed in all undifferentiated small blue cell SM. The pigmented SM were predominantly HMB45-negative. The strong HMB45 staining in amelanotic small blue cell SM is explained by the reaction of HMB45 antibody with an oncofetal antigen found in immature melanosomes. In these poorly differentiated amelanotic malignant melanomas, antibody to HMB45 proved to be a superb diagnostic marker. We therefore strongly advocate the inclusion of HMB45 antibody in the panel of antibodies for initial work-up of undifferentiated mucosal neoplasms, since a negative S-100 stain in small biopsy material may result in incorrect classification of these neoplasms.

Adult↗

Keratoacanthoma: a clinically distinct variant of well differentiated squamous cell carcinoma.

Keratoacanthomas are distinct skin lesions that occur most often as solitary tumors in sun-exposed areas in elderly, fair-skinned patients. Clinically, these tumors are characterized by a rapid onset and regression within months. Keratoacanthomas display distinct histological features including a keratin-filled crater lined by a proliferating squamous epithelium. Cytologically, there may be overlap with classical well differentiated squamous cell carcinoma. Rarely, otherwise typical keratoacanthomas show intravascular and perineural invasion and lymph node metastases. Keratoacanthomas should, therefore, be considered to be a clinically distinct variant of well differentiated squamous cell carcinoma capable of spontaneous regression. This view is supported by their common etiology, occasional concurrent occurrence, and a multitude of studies revealing no substantial differences between these two lesions. Regression is immunologically mediated and activated by a variety of molecular mechanisms. Considering the common nature of keratoacanthomas and well differentiated squamous cell carcinomas, and the lack of any features predicting prognosis, surgical excision of keratoacanthoma is advisable.

Adult↗

Mixed connective tissue disease. A clinical, histologic, and immunofluorescence study of eight cases.

A study of the cutaneous eruptions of eight patients with mixed connective tissue disease (MCTD) was performed to better characterize its dermatopathology and to explore a role for the membrane attack complex of complement C5b-9 in lesional pathogenesis. Nine lesional skin biopsies were obtained from eight patients with MCTD and analyzed by conventional light microscopy. Direct immunofluorescence (IF) and indirect IF using a monoclonal antibody to C5b-9 were applied in six and five cases respectively. The biopsied cutaneous eruptions were characterized clinically as photo-distributed erythematosus annular and/or papulosquamous lesions mimnicking subacute cutaneous lupus erythematosus (SCLE) in five of eight patients as an ill-defined, telangiectatic, scaly patch on the face in one patient, palpable purpura in one patient, and dorsal hand blisters resembling porphyria cutanea tarda (PCT) in another. With the exception of the latter two patients, the histology appeared similar, comprising a cell poor and/or lichenoid interface dermatitis with suprabasilar exocytosis around necrotic keratinocytes in the absence of deep periadnexal or perivascular extension or conspicuous follicular plugging, a pattern similar to that of SCLE. However, the lesions differed from SCLE by virtue of vasculopathic alterations comprising vascular ectasia, hypovascularity, and/or luminal thrombosis confined to the superficial vascular plexus and a sclerodermoid tissue reaction, the latter seen in two cases. One biopsy showed a pustular leukocytoclastic vasculitis (LCV). In another case, a biopsied hand blister demonstrated a PCT-like appearance histologically, namely, pauci-inflammatory subepithelial blister formation with hyalinization of dermal papillae capillaries accompanied by an LCV. There was nuclear keratinocyte decoration with IgG and C5b-9 in all cases studied, accompanied by a positive lupus band test in two cases and homogenous deposition of immunoreactants along the dermoepidermal junction and within vessels in the PCT-like eruption. Granular vascular decoration with immunoreactants including C5b-9 was seen in two LCV cases and in two biopsies from rashes clinically mimicking SCLE. Although the epidermal pathology of MCTD mimicks that of SCLE, a concomitant vasculopathy paralleling that seen in skin lesions of dermatomyositis distinquishes the dermatopathology of MCTD from that of SCLE. Corroborating the role of microangiopathy in the pathogenesis of the skin lesions of MCTD was the demonstration of C5b-9 in blood vessels. The deposition of C5b-9 in keratinocytes may explain the pattern Of IgG decoration of keratinocytes; the formation of plasmalemmal pores may permit binding of immunoglobulin to antigens in the nucleus and/or cytosol. The C 5b-9 complex may be the effector mechanism of epithelial and/or endothelial cell injury in MCTD or may serve to augment the effects of antibody-dependent cellular cytotoxicity.

Adult↗

Value of exfoliative cytology in differential diagnosis of epithelial hyperplastic lesions of the larynx.

In a comparative random study we examined material from suspicious laryngeal lesions from 85 patients. Material was obtained simultaneously by exfoliative cytology and biopsy. The diagnoses included keratosis, papilloma/papillomatosis, dysplasia/carcinoma in situ and invasive carcinoma. In each case we were able to demonstrate the cytological diagnostic criteria in the respective histological specimens. We illustrate this in the paper with some examples. Due to the excellent correlation between cytology and histology we are convinced that exfoliative laryngeal cytology is very significant in differential diagnosis of epithelial hyperplastic lesions.

Biopsy↗

Lateral neck cysts--the branchial theory revisited. A critical review and clinicopathological study of 97 cases with special emphasis on cytokeratin expression.

Theories regarding the origin of lateral neck cysts (LNC) range from congenital branchial pouch abnormalities to acquired salivary gland inclusions within lymph nodes. We analyzed 97 LNC histologically and evaluated their cytokeratin (CK) profile in a search for their derivation. 77/97 LNC were located in soft tissues, 20/97 within lymph nodes. LNC of young patients and of recent symptomatic presentation in older patients were lined by respiratory epithelium with scant lymphoid tissue, with expression of "simple epithelial" CK in ciliated cells and bimodal expression of "simple" and "stratified-epithelial-type" CK in basal cells. In longer standing symptomatic LNC, respiratory epithelium alternated with transitional-type pseudostratified epithelium with intraepithelial Langerhans cells and lymphoid hyperplasia, or consisted exclusively of squamous epithelium. We propose that respiratory epithelium is the "native" epithelium of LNC and squamous metaplasia results from inflammation induced stem cell hyperplasia in respiratory epithelium, evidenced by co-expression of "simple" and "stratified-epithelial-type" CK in all cells of transitional-type pseudostratified epithelium, the early stage in metaplastic transformation. Respiratory epithelium predominates in early LNC, lines pharyngeal tonsils and the recessus tonsillo-tubalis, and is a minor constituent of palatine tonsil but is not present in salivary glands. None of the LNC contained dysplasia, atypia, or carcinoma, or were associated with a primary carcinoma of tonsils or head and neck. We demonstrate that LNC arise from developmental remnants (congenital) of the 2nd branchial pouch, which may lie dormant for many years. Symptomatic enlargement, squamous metaplasia and lymphoid hyperplasia ensue as a consequence of immunologic stimulation a development reflected in hyperplastic palatine tonsils.

Adolescent↗

Granuloma annulare and necrobiosis lipoidica tissue reactions as a manifestation of systemic disease.

Granuloma annulare (GA) and necrobiosis lipoidica (NL) are generally considered to be idiopathic cutaneous palisading granulomatous dermatitides. There are sporadic reports of such lesions occurring in patients with coexistent systemic diseases other than diabetes mellitus. Having encountered 49 patients whose skin biopsies showed GA or NL lesions in the setting of extracutaneous disease, the authors set out to assess their clinical and histopathological findings to determine if any parameters were predictive of underlying systemic disease. Fifty-two skin biopsies from 49 patients having either GA or NL in whom there was a clinical history of an associated systemic disease were analyzed by light microscopy. The main systemic disease associations were rheumatologic, endocrine, hematologic, infectious, and inflammatory bowel diseases, ANCA positive vasculitic syndromes, and sarcoidosis. The clinical and histomorphological features were compared with those of a control group of patients whose skin biopsies showed GA or NL and in whom there was no history of extracutaneous disease. For the systemic disease group, patients were selected either retrospectively or prospectively from 160,000 cases accessioned in a 24-month period in the dermatopathology databases of Pathology Services, Inc (Cambridge, MA) and Central Medical Laboratories (Winnipeg, Canada). All systemic disease cases from the former service were analyzed blindly by the second author and from the latter service were analyzed blindly by the first author. Patients in the control group were obtained retrospectively from the Pathology Services Inc. database by the authors. The location of the lesions was atypical in 30 of 34 biopsies from systemic disease patients with a GA tissue reaction versus 10 of 22 biopsies of GA in the control group (P = .001). Six of 18 biopsies from patients with NL tissue reactions in the systemic disease group showed an atypical location, versus only 1 of 9 biopsies of NL from the control group (P = .19). The clinical diagnostic considerations were much broader in the systemic disease group versus the control group and included vasculitis, panniculitis, and connective tissue diseases including morphea in the former. In 22 of 34 GA biopsies and 16 of 18 NL biopsies from the systemic disease group, an active vasculopathy of leukocytoclastic, granulomatous, or thrombogenic subtypes was demonstrable. None of the GA or NL biopsies from the control group showed a similar active vasculopathy. An active vasculopathy was predictive of systemic disease in patients having either a GA-like or an NL-like tissue reaction (P < .001). Fifteen of 34 GA and 7 of 18 NL biopsies in the systemic diseases group showed extravascular neutrophilia in contrast to 3 of 22 GA (P = .02) biopsies and 2 of 9 NL (P = .33) biopsies in the control group. The finding of an active vasculopathy in a skin biopsy specimen showing a GA- or NL-like tissue reaction, particularly in the setting of an atypical clinical presentation both with respect to the location and appearance of lesions, should prompt consideration of an underlying systemic disease, as should extravascular neutrophilia in a skin biopsy showing a GA-like tissue reaction.

Adult↗