IL-36α and IL-36γ expressions in the differential diagnosis of palmoplantar psoriasis and palmoplantar eczema: A retrospective histopathologic and immunohistochemical study.

BACKGROUND: Diagnosing hyperkeratotic lesions on the palms and soles is often challenging for both clinicians and pathologists. Interleukin (IL)-36 cytokines play an important role in the pathogenesis of psoriasis. METHODS: We retrospectively re-evaluated hematoxylin-eosin-stained biopsy specimens of 30 patients with clinically diagnosed palmoplantar psoriasis (PP) and 30 patients with palmoplantar eczema (PE), and then performed IL-36α and IL-36γ immunohistochemistry. RESULTS: Among the histopathologic features, thinning of the rete ridges and vertical alternation of parakeratosis and orthokeratosis had the highest positive predictive value (PPV) in diagnosing PP (72.7% and 69.3%, respectively). Immunohistochemically, patients with PP predominantly showed diffuse or focal strong expression with IL-36α and IL-36γ staining in the upper layers of the epidermis (86.7% and 83.3%, respectively). The comparison of the mean IL-36α and IL-36γ expression scores significantly differed between PP and PE (P < .001). Among all histopathologic and immunohistochemical features, diffuse strong expression of IL-36α and IL-36γ staining had the highest PPVs in favor of a diagnosis of PP (75% and 76.7%, respectively). CONCLUSIONS: Our data suggest that IL-36α and IL-36γ immunohistochemistry can be used in the differential diagnosis of PP and PE.

Solitary Subungual Orf.

Orf-ecthyma contagiosum-is an endemic cutaneous disease caused by parapoxvirus that is transmitted via direct contact with contagious animals. The lesions are located frequently on the hands and fingers. Subungual presentation of orf is very rare. We report a case of solitary subungual orf. Suspicious subungual nodular lesions may be cases of orf, especially in endemic areas. Orf disease should be considered in the differential diagnosis of subungual nodular lesions to avoid unnecessary surgical interventions.

Tissue eosinophil levels as a marker of disease severity in bullous pemphigoid.

BACKGROUND: Eosinophils play an important role in bullous pemphigoid (BP) pathogenesis. Although tissue infiltration with eosinophils has been known for a long time, there is a lack of knowledge about the relationship between tissue eosinophil levels and disease severity and clinical characteristics of the patients. METHODS: Fifty-nine patients diagnosed with BP between January 2008 and December 2018 were reviewed. Haematoxylin-Eosin (H&E)-stained preparations were re-evaluated in terms of tissue eosinophil levels. For disease severity, Bullous Pemphigoid Disease Area Index (BPDAI) was used. The relationship between tissue eosinophil levels and disease severity and clinical features were evaluated. RESULTS: Erosion/blister and urticaria/erythema BPDAI scores were higher in the group with high tissue eosinophil level than the group with low tissue eosinophil level. Tissue and peripheral blood eosinophil count were correlated with total urticaria/erythema BPDAI scores. There was no correlation between blood and tissue eosinophil count. The mortality rate was 64.7% vs 44.0% in the high vs low tissue eosinophil groups. Tissue eosinophil levels were high in patients with BP accompanying neurological disease. CONCLUSIONS: Tissue eosinophil count and peripheral blood eosinophil count were correlated with disease severity in BP. Tissue eosinophil levels were also high in patients with BP accompanying neurological disease.

Evaluation of clinicopathological and treatment characteristics of 80 patients with acquired perforating dermatosis.

Acquired perforating dermatosis (APD) is a group of a rare dermatological disorder characterized by elimination of dermal connective tissue through epidermis. We aimed to evaluate the characteristics of patients diagnosed with APD and to determine the differences in comorbidities according to subtypes of APD. A retrospective, observational, cross-sectional study was designed. Patients diagnosed with APD between January 2008 and January 2019 were reviewed. Eighty patients were included in the study. 61.2% (n = 49) of the patients were female and 38.8% (n = 31) were male with a mean age of 58.4 ± 12.5 years. 82.5% (n = 66) of the patients were diagnosed with reactive perforating collagenosis (RPC) and 17.5% (n = 14) of perforating folliculitis (PF). The most common concomitant disease was diabetes mellitus (82.5%). 5.0% of the patients had malignancy. The comorbidity rate in RPC group was higher than PF (P < .05). Topical steroid was the most frequently (90.0%) used treatment. Complete response was obtained 55.0% of patients. Exitus was observed in 23.8% (n = 19) of patients in a mean 17.6 ± 25.7 months follow-up period. APD may be associated with many diseases. Comorbidities are more frequent in RPC group. This situation warns us to evaluate patients with RPC in more detail for underlying diseases. High mortality rate related to the underlying systemic diseases suggests being careful in terms of mortality in patients diagnosed with APD.

Adalimumab-induced scalp psoriasis with severe alopecia.

In recent years, with the increase usage of tumor necrosis factor (TNF) inhibitors, more side effects have revealed. The incidence of paradoxical psoriasis (psoriasis vulgaris, palmoplantar pustulosis, scalp psoriasis, or their combinations) ranges from 1 to 5%; however alopecia due to anti-TNF-α-induced scalp psoriasis, rarely reported in the literature. We report a 37-year-old woman who developed palmoplantar pustulosis and scalp psoriasis with severe alopecia after 2 months of treatment with adalimumab for chronic plaque psoriasis. Biopsies from the palmar and scalp lesions showed psoriasiform changes. Adalimumab treatment was discontinued, and methotrexate was started (15 mg/weekly, subcutaneously) with topical adjuvant agents. A dramatic improvement was seen in both the skin and scalp with complete hair regrowth in 1 month. We conclude that, in anti-TNF-α-induced scalp psoriasis, suspension of anti-TNF-α agent and systemic and topical treatments should be considered to avoid scarring alopecia.

A new immunohistochemical marker, insulinoma-associated protein 1 (INSM1), for Merkel cell carcinoma: Evaluation of 24 cases.

Merkel cell carcinoma (MCC) is an uncommon primary neuroendocrine carcinoma of the skin. Nowadays, pathologists are required to perform immunohistochemistry to demonstrate neuroendocrine and epithelial differentiation for diagnosis of MCC. Insulinoma-associated protein 1 (INSM1) is a zinc-finger transcription factor expressed in tissues undergoing terminal neuroendocrine differentiation, and INSM1 immunohistochemistry is a well-validated nuclear marker of neuroendocrine differentiation. We evaluated 24 cases of MCC for the expression of INSM1 and compared it with frequently used neuroendocrine markers, Chromogranin A, Synaptophysin, and CD56. INSM1 was positive in all cases, and its expression was stronger, more extensive, clean and homogeneous compared to other markers. As a consequence, INSM1 can be used to serve as a solitary marker for neuroendocrine differentiation due to high sensitivity and specificity in MCC cases.

Solitary noninfiltrating angiolipoma on the finger, an unusual localization.

Angiolipoma, a subtype of lipoma, is a benign adypocytic soft tissue tumor composed of mature adipose tissue and small vascular proliferations. This entity makes up 5-17% of all lipomas. The diagnosis is made by clinical and pathological examination, ultrasonography, and/or magnetic resonance imaging (MRI). It is generally an encapsulated tumor (noninfiltrative), but rarely has an infiltrative form. Angiolipoma mostly occurs on the trunk and extremities with male predominance. The forearm is the most frequent location for angiolipomas. It is very rarely seen on the fingers. Herein, we report a patient with solitary noninfiltrating angiolipoma on a finger. The patient was treated with surgical excision and no recurrence has been noted over one year of observation.

Superficial acral fibromyxoma in the heel with new vascular features on dermoscopy.

Superficial acral fibromyxoma (SAFM) is an uncommon mesenchymal soft tissue tumor with a predilection for the acral extremites and nail bed involvement. SAFM is diagnosed with clinicopathological and immunohistochemical examination. Awareness of this rare tumor is important because of amounts of benign and malignant neoplasms. We report a case of SAFM in a rare localization in the heel with a new finding on dermoscopy.

Primary breast carcinomas with neuroendocrine features: Clinicopathological features and analysis of tumor growth patterns in 36 cases.

Primary breast carcinoma with neuroendocrine features (NEBC) is an uncommon tumor. In the classification of WHO 2012, these tumors were categorized as: 1- neuroendocrine tumor, well-differentiated; 2- neuroendocrine carcinoma, poorly differentiated/small cell carcinoma; and 3- invasive breast carcinoma with neuroendocrine differentiation. In this study, we reviewed NEBC except poorly differentiated/small cell carcinoma variant in order to define the morphological growth patterns and cytonuclear details of these tumors. All breast surgical excision materials between 2007 and 2016 were re-evaluated in terms of neuroendocrine differentiation. Thirty-six cases showing positive staining for synaptophysin and/or chromogranin A in ≥50% of tumor cells were included in the study. All cases were female with a mean age of 67.4. Mean tumor diameter was 26 mm. Multifocality was noted in 5 cases. Grossly, they were mostly infiltrative mass lesions. T stages, identified in 34 cases, were as follows: 13 cases with pT1; 19 pT2 and 2 pT3. We described schematically 4 types of patterns depending on predominant growth pattern, except one case: 1) Large-sized solid cohesive groups (6 cases), 2) Small- to medium-sized solid cohesive groups with trabeculae/ribbons and glandular structures (6 cases), 3) Mixed growth patterns (20 cases), 4) Invasive tumor with prominent extracellular and/or intracellular mucin (3 cases). The tumor cells were mostly polygonal-oval with eosinophilic/eosinophilic-granular cytoplasm. The nuclei of tumor cells were mostly round to oval with evenly distributed chromatin. Only 5 cases showed high grade nuclear and histological features. Molecular subtypes of the cases were as follows: 33 luminal A, 2 luminal B, and 1 triple negative. NEBC should come to mind when a tumor display one of the morphological patterns described above, composed of monotonous cells with mild to moderate nuclear pleomorphism and abundant eosinophilic/eosinophilic granular or clear cytoplasm, especially in elderly patients.

Intravascular Papillary Endothelial Hyperplasia of the Foot.

A case of intravascular papillary endothelial hyperplasia is presented. This proliferation usually forms inside thrombotic processes. It is critical to be able distinguish these lesions from low-grade angiosarcomas because they can have similar pathologic findings.

Intralymphatic nevus cells in benign nevi.

The histogenesis of nevus cell aggregates in lymph nodes lesion is controversial, and various hypotheses have been used to explain their origin. One of them is the transport of cells from cutaneous nevi or lesions to lymph nodes, called mechanical transport theory. We investigated in our cases of benign nevi to obtain evidence to substantiate this theory. A total of 369 benign cutaneous nevi were prospectively evaluated in excisional biopsy samples. Immunohistochemical stainings for CD31 and podoplanin (D2-40) were performed in the cases with intralymphatic nevus cell aggregate (ILNA), suspected for ILNA, and/or intralymphatic nevus cell protrusion. A total of 13 ILNAs were found in 10 patients. Six ILNA were verified with their histology as well as immunohistochemically with D2-40 and CD31. Protrusions of nevus cells inside the lymphatics (intralymphatic nevus cell protrusion) were seen in all cases of ILNA and also in 27 nevi where an ILNA was not observed. In most nevi, the perilymphatic orientation of nevus cells and their affinity to the lymphatics were observed. We suggested that ILNAs can be dislodged with local minor trauma and be carried inside the lymphatic vessel to the draining lymph node. Besides, whether ILNA or not, nevus cells could also move toward lymphatic spaces with mechanical effects due to their affinity to lymphatics and their localizations that are very close to the endothelium. Our findings might support the mechanical transport theory.

The relationship between diverticula and low-grade mucinous neoplasm of the appendix. Does the diverticulum play a role in the development of periappendicular mucin deposition or pseudomyxoma peritonei?

Prevalences of diverticulum and low-grade mucinous neoplasm (LGMN) were reported as 0.04-2% and less than 1% in the appendix. In this study, the frequency of diverticulum in LGMN cases, the relationship between diverticula and periappendicular mucin, and the possible role of diverticula in pseudomyxoma peritonei pathogenesis were researched. Through systematic review and targeted search, 38 LGMN and 96 diverticula were identified, frequencies and relationship between diverticulum and LGMN were analysed. Diverticulum and LGMN were determined in 4.8% and 1.04%, respectively, of 1922 appendectomy materials specifically grossed by the same pathologist. The prevalence of diverticulum was higher in our study than literature. The difference may be due to detailed macroscopic examination. Diverticulum was detected in 60% of LGMN cases. The rate of diverticulum was found to be significantly higher in LGMNs than non-neoplastic diverticulum (p < 0.001). Periappendicular mucin deposition was significantly more frequent in LGMN cases with diverticulum than in other groups (p < 0.05). Follow-ups were available in 18 patients; none of them had mucin deposition in the peritoneal cavity. We detected that periappendicular mucin was highly associated with diverticula in LGMN cases. Periappendicular acellular mucin deposition may not give rise to pseudomyxoma peritonei. We may think that mucin could move out of the appendix through the diverticulum rather than neoplastic spread in some of these cases.

Vestibular papillomatosis: An important differential diagnosis of vulvar papillomas.

Most authors believe that vestibular papillomatosis (VP) is an anatomical variant of the vestibular mucosa. But VP is sometimes misdiagnosed as genital warts and this can lead to aggressive investigations, therapy, and anxiety in patients. We present a patient with VP. Dermoscopy and reflectance confocal microscopy (RCM) were performed to differentiate VP from other papilomatous diseases of the vulva.

Zosteriform pemphigoid after zoster: Wolf's isotopic response.

The Wolf isotopic response describes the occurrence of a new, unrelated disease that appears at the same location as a previously healed disease. The most common primary skin disorder of this phenomenon is herpes zoster and less frequently, herpes simplex. We report a case of 79-year-old woman who have bullous pemphigoid (BP) with dermatomal distribution that developed at the site of previously healed herpes zoster. Based on clinical, histological and immunofluorescence findings, the patient was diagnosed with localized BP in a site of prior herpes zoster. BP developing at the site of healed herpes zoster is the first reported case. Recognition of this phenomenon is important for correct clinicopathologic diagnosis and may improve our understanding of the underlying pathophysiologic processes.

Intravascular/Intralymphatic Histiocytosis: A Report of 3 Cases.

Intravascular/intralymphatic histiocytosis (IV/ILH) is a rare, reactive cutaneous condition, with uncertain pathogenesis. It may be associated with various inflammatory and neoplastic diseases. Although the clinical presentation is various, the biopsies reveal dilated vessels, mostly lymphatics, containing aggregates of histiocytes within their lumina. We described 3 cases of IV/ILH with different clinical presentations. In the first case, the patient presented with lymphedema in the genital region without any underlying disease. However, the second and third cases had reticular erythematous skin lesions. The second case had common variable immunodeficiency disease, rheumatoid arthritis, inflammatory bowel disease, and a history of a lymphoproliferative lesion. The third case had metal prostheses at both his right and left knees. In all these 3 cases, histopathologic and immunohistochemical findings were similar to each other and to those cases reported in the literature. In addition, the third case was admixed with reactive angioendotheliomatosis. In the second case, the endothelium of the ectatic vessels expressed CD31 and CD34, but not D2-40/podoplanin, pointing out that these vessels were blood vessels rather than lymphatics, differing from the other 2 cases. In conclusion, we believe, the most convincing statement about IV/ILH is that it is not a distinct clinicopathologic entity, but a histopathologic feature found as a part of a constellation of inflammatory changes or many other conditions.

Total knee arthroplasty for the management of joint destruction in tuberculous arthritis.

PURPOSE: The purpose of this study was to evaluate our experience to clarify the suggestion that there should be a significant disease-free interval before total knee arthroplasty (TKA) and to determine the correct timing of surgery for reconstruction of the joint destruction in patients suffering from tuberculous arthritis. METHODS: Twelve patients with advanced joint destruction and tuberculous arthritis of the knee with recent onset were reviewed in this study. The time interval from our diagnosis of active infection to arthroplasty averaged 4 ± 1.5 months. Histopathology of the biopsy specimens revealing granulomatous lesions, including epithelioid histiocytes surrounded by lymphocytes, confirmed the diagnosis of each patient. A primary knee prosthesis was performed in seven knees. In five knees, there was severe bone loss after the extensive debridement of the entire joint, and thereafter, revision prosthesis was preferred to preserve the joint line. Patients were given post-operative antituberculous treatment for a total of 1 year, whereas for three patients, whose erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values remained above normal by the sixth month, the chemotherapy was continued for up to 18 months. The Knee Society TKA roentgenographic evaluation and scoring system was used for radiological evaluation of the knees. Clinical evaluation of the knees was done preoperatively and at the time of the most recent follow-up using the American Knee Society Scoring System. RESULTS: Within the average follow-up period of 6.1 ± 1.8 years, no reactivation of tuberculous infection was found in any of the patients. ESR was normal, less than 20 mm/h, after a mean time of 5.5 ± 2.0 months. The CRP was normal, less than 0.8 mg/dl, after a mean time of 4.6 ± 1.3 months. At the most recent follow-up, the average knee score improved from 32.4 ± 19.4 to 83.4 ± 14.0 points (p < 0.05), and the average function score improved from 33.3 ± 11.9 to 86.6 ± 7.7 points (p < 0.05). Ten knees showed good integrity, and no radiolucent lines were found in the bone-prosthesis interface in relation to any component. Radiolucent lines were apparent on the tibial side in two knees. They were less than 1 mm thick and non-progressive, and clinically, there was no evidence of loosening of the component. Culture specimens were positive for five patients. CONCLUSIONS: TKA is a safe procedure for tuberculous arthritis with recent onset providing symptomatic relief, functional improvement and early return to activity when performed in correct time. A long disease-free interval should not be a prerequisite for arthroplasty. Wide surgical debridement is the mainstay to eradicate the disease, and post-operative antituberculous chemotherapy controls the residual foci. LEVEL OF EVIDENCE: IV.

Perineural differentiation in neurotized nevi.

BACKGROUND: Perineuriomatous melanocytic nevi are rare and this may indicate the similar embryological source of melanocytes and peripheral nerves in the neural crest. Neurotized melanocytic nevi may resemble nerve sheath tumors histologically, and show schwannian differentiation. However, literature on whether neurotized nevi differentiate into perineural cells is controversial. We examined our cases of neurotized nevi for evidence of perineural differentiation. MATERIALS AND METHODS: A total of 100 benign nevi with large neurotized component (microscopically involved a low power field 4.2 mm in diameter) were prospectively evaluated in excisional biopsy samples. Immunohistochemical stainings for EMA, Claudin1, Glut1 and neurofilament were performed. RESULTS: Perineural differentiation was immunohistochemically detected in the neurotized component of the nevi in 61% of the cases with EMA and in all the cases with Glut1 and Claudin1. Axonal differentiation was not detected with neurofilament. The expression pattern, especially with Glut1, was usually in form of partial or complete staining surrounding the Meissner's corpuscle-like structure (MCLS). Also, a linear/curvilinear staining pattern was observed particularly with Claudin1. A diffuse staining pattern with EMA, Glut1 and Claudin1 was detected in a case with a microscopically distinct whorl structure, and in which spindle cells are separated from the superficial epithelioid melanocytes with an abrupt transition histologically. These findings of the case are compatible with previous reports of perineuromatous nevus. CONCLUSION: Perineural differentiation is not uncommon and immunohistochemically observed in all nevi with a relatively large component of neurotization. To prevent misdiagnosing desmoplastic melanoma and overtreating patients, it is crucial to be aware of perineuromatous nevi.

Could serum ß-hCG levels and gestational age be the indicative factors for the prediction of the degree of trophoblastic invasion into tubal wall in unruptured ampullary pregnancies?

OBJECTIVE: To evaluate the predictive value of gestational age and maternal serum ß-hCG concentration for the determination of the depth of trophoblastic invasion into the tubal wall. METHODS: This is a retrospective trial conducted on women with a diagnosis of ampullary pregnancy (71) who were submitted to salpingectomy. Serum ß-hCG measurements were obtained at the initial admission of hospital. Histological investigation was performed by a single well-experienced pathologist who was blind to the clinical and laboratory characteristics of the patients. Ampullary pregnancy was classified histologically according to the depth of trophoblastic infiltration into tubal wall: trophoblast limited to the tubal mucosa (stage I), extended to muscularis layer (stage II) and complete tubal wall infiltration up to serosal layer (stage III). RESULTS: There was a significant difference in maternal serum ß-hCG concentrations regarding the histological stages of trophoblastic invasion. The serum ß-hCG concentrations that the best predicted for stage III trophoblastic invasion was 6,475 mIU/ml, with a sensitivity of 100 %, a specificity of 92 %. CONCLUSION: The depth of trophoblastic tissue infiltration into tubal wall is correlated with serum ß-hCG levels, but not with gestational age. These findings may explain the reason for conservative management failure of EP in women with high ß-hCG concentrations.