Sparse Lymphocytic Infiltrate Research Articles

Mycosis Fungoides and Granulomatous Slack Skin: A Single Entity With Distinct Clinical Phenotypes.

Granulomatous cutaneous T-cell lymphoma includes mycosis fungoides with significant granulomatous inflammation (GMF) and granulomatous slack skin (GSS), listed in the WHO classification as a subtype of mycosis fungoides (MFs).1 These overlapping entities have shared clinical and histopathologic features which can present a diagnostic challenge. The dominance of the granulomatous infiltrate and the often sparse lymphocytic infiltrate frequently with minimal cytological atypia are features that distract from the correct diagnosis, even when raised by the clinician. We describe the clinical and histopathologic characteristics of 3 cases of granulomatous cutaneous T-cell lymphoma, illustrate the close clinical and pathologic relationship between GMF and GSS and emphasize the diagnostic difficulties that the granulomatous infiltrate can present. Furthermore, we demonstrate, for the first time, considerable elastolysis in a significant proportion of classical (Alibert-Bazin) MF lesions and therefore postulate that the differences observed between GMF and GSS are one of degree and secondary to their anatomic location rather than reflecting meaningful separate entities.

Primary hyperoxaluria: A case report

Renal failure can occasionally be caused by oxalate nephropathy. Glyoxylate metabolism abnormalities and particular hepatic enzyme deficits are the causes of primary hyperoxaluria (PH). Increased intestinal absorption, an excessive diet or an increased intake of oxalate precursors can all result in secondary hyperoxaluria. A 13-month old male child with high blood creatinine, low sodium, low calcium levels, high uric acid and low urine specific gravity is the subject of this research. Medullary papillary calcification was detected using sonography (nephrocalcinosis). Calcium oxalate crystals, sparse lymphocytic infiltration and interstitial fibrosis were seen on a renal biopsy. The patient was put on peritoneal dialysis, progresses to anuria and expired due to renal failure.

Leiomyoma-like Morphology in Metastatic Uterine Inflammatory Myofibroblastic Tumors

Uterine inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms that frequently harbor ALK gene rearrangements and have a low risk of metastasis. We reported 3 of these tumors mimicking the appearance of leiomyoma in their recurrence. These patients were 34, 43, and 45 years old. Two uterine tumors demonstrated classic morphology, with combined myxoid, compact fascicular, and hyalinized patterns and spindled cells with bipolar cytoplasmic processes, moderate atypia, and lymphoplasmacytic inflammatory infiltrates. The third had a “leiomyoma-like” appearance, with fascicles of plump spindled cells and a sparse lymphoplasmacytic infiltrate. ALK immunohistochemistry was positive in all the tumors, and all demonstrated ALK rearrangements using fluorescence in situ hybridization (n = 2) and/or RNA sequencing (n = 2). Two classic IMTs recurred at 3 and 50 months in the lung and abdomen, respectively, and recurrent tumors had a “leiomyoma-like” appearance, with 0 and 1 mitosis per 10 high-power fields, no inflammation in 1, and a sparse lymphocytic infiltrate in the other. ALK was positive in both tumors; 1 with available tissue showed an IGFBP5::ALK fusion using RNA sequencing. The third patient, who had a “leiomyoma-like” uterine tumor, experienced multiple recurrences, first in the abdomen at 100 months showing a similar appearance. Subsequent recurrence at 105 months showed transmural invasion of the sigmoid colon and a similar microscopic appearance but with the addition of infiltrative borders, moderate cellularity, mild-to-moderate atypia, and 10 mitoses per 10 high-power fields. Both recurrences were positive for ALK, and RNA sequencing revealed the same ACTG2::ALK fusion transcript identified in the primary tumor. The patient was treated with crizotinib, resulting in prolonged clinical remission, with no evidence of disease at 168 months from the initial surgery. Although “leiomyoma-like” uterine IMTs have been recently described, to our knowledge, this is the first report of recurrence of these tumors and the first report of a “leiomyoma-like” appearance in the recurrences of conventional uterine IMTs. A low threshold for performing ALK immunohistochemistry on recurrent uterine tumors can identify patients who may benefit from tyrosine kinase inhibitors.

Persistent Generalized Cutis Marmorata Telangiectatica Congenita with Venectasia.

Persistent Generalized Cutis Marmorata Telangiectatica Congenita with Venectasia.

Granulomatöse Dermatosen

The group of granulomatous dermatoses refers to a multitude of clinically different diseases, which are characterized by a histopathologically similar pattern of inflammation. The cause of granulomatous inflammatory reactions can be infections and also noninfectious stimuli, such as cell disintegration or foreign bodies. The aim of this immunological defence reaction is encapsulation in order to prevent further spread and delimitation from healthy tissue. This is histologically expressed as a granuloma in the sense of a circumscribed aggregation of histiocytes and multinucleated giant cells mostly in dermal connective tissue. The following can be histologically differentiated: sarcoid granuloma characterized by a sparse lymphocytic inflammatory infiltrate and tuberculous granuloma with central necrosis and denser lymphocytic inflammatory infiltrate. Neutrophilic granulocytes together with macrophages occur in suppurative granulomas and palisaded granulomas are characterized by peripherally arrayed macrophages.

Vestibulovaginal Sclerosis Versus Lichen Sclerosus.

To determine if vestibulovaginal sclerosis and lichen sclerosus (LS) are 2 distinct entities. Biopsies obtained from the vagina or vulvar vestibule that contained abnormal subepithelial collagen were reviewed. Cases were categorized either as LS or vestibulovaginal sclerosis based on presence or absence of basal layer degeneration and lymphocytic infiltrate. Clinical data collected included examination findings, biopsy site and indication, previous vulvovaginal surgery, medications at time of biopsy, vulvar LS, treatment, and response. There were 15 cases with a mean age of 62 yr (range: 32–86 yr); 12 (80%) specimens were from vestibule and 3 from vagina. Nine cases were categorized as LS because of lymphocytic infiltrate in combination with basal layer degeneration, of these 8 had LS elsewhere on vulvar skin. Six cases were classified as vestibulovaginal sclerosis and had an absent or sparse lymphocytic infiltrate and essentially normal epithelium; none of these had vulvar LS. While vestibulovaginal sclerosis and lichen sclerosus are distinguishable clinically and histopathologically, further studies are needed to determine if vestibulovaginal sclerosis is a subset of LS or a different condition.

Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors.

In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Chroscinski et al., 2015) that described how we intended to replicate selected experiments from the paper "The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors "(Willingham et al., 2012). Here we report the results of those experiments. We found that treatment of immune competent mice bearing orthotopic breast tumors with anti-mouse CD47 antibodies resulted in short-term anemia compared to controls, consistent with the previously described function of CD47 in normal phagocytosis of aging red blood cells and results reported in the original study (Table S4; Willingham et al., 2012). The weight of tumors after 30 days administration of anti-CD47 antibodies or IgG isotype control were not found to be statistically different, whereas the original study reported inhibition of tumor growth with anti-CD47 treatment (Figure 6A,B; Willingham et al., 2012). However, our efforts to replicate this experiment were confounded because spontaneous regression of tumors occurred in several of the mice. Additionally, the excised tumors were scored for inflammatory cell infiltrates. We found IgG and anti-CD47 treated tumors resulted in minimal to moderate lymphocytic infiltrate, while the original study observed sparse lymphocytic infiltrate in IgG-treated tumors and increased inflammatory cell infiltrates in anti-CD47 treated tumors (Figure 6C; Willingham et al., 2012). Furthermore, we observed neutrophilic infiltration was slightly increased in anti-CD47 treated tumors compared to IgG control. Finally, we report a meta-analysis of the result.

Generalized benign cutaneous reaction to cytarabine

Cytarabine-induced toxicity manifests as various cutaneous morphologies. A generalized papular purpuric eruption has not been well described. We aimed to characterize a distinct cytarabine-related eruption. We reviewed all cases of cytarabine-related toxicity with papular purpuric eruptions or violaceous erythema at the University of California, San Francisco between 2006 and 2011. Sixteen cases were identified. The eruption began as erythematous papules that evolved into coalescing purpuric papules and plaques. It had affinity for intertriginous areas, neck, ears, and scalp. Pruritus was common, but no systemic complications were documented. Thirteen patients (81.3%) developed the eruption after completion of chemotherapy. Differential diagnosis often included viral exanthem (62.5%), drug eruption (50%), and vasculitis (37.5%). Histopathology was nonspecific but commonly demonstrated sparse lymphocytic infiltrates, spongiosis, and/or red cell extravasation. Importantly, the eruption was neither predicted by past cytarabine exposure nor predictive of future recurrence. This is a review of cases from a single institution. Observation was limited to acute hospitalization, however, charts were reviewed for subsequent reactions on rechallenge. The eruption described herein represents a specific skin-limited reaction to cytarabine. Awareness of its characteristic morphology, distribution, and timeline will aid in clinical diagnosis. Reassurance concerning its benign nature will prevent unnecessary intervention or cessation of chemotherapy.

Oxidative myocardial damage in human cocaine-related cardiomyopathy.

The pathogenesis of cocaine-related cardiomyopathy (CCM) is still unclear. Oxidative damage from cocaine-generated reactive oxygen species (ROS) overcoming myocardial antioxidant reserve has been hypothesized by experimental studies. Ten (2.3%) of 430 consecutive cases with dilated cardiomyopathy (DCM) were attributed to CCM. Endomyocardial biopsies from CCM were retrospectively investigated with histology, electron microscopy, immunohistochemistry (graded 0-3), and Western blot analysis for inducible nitric oxide synthase (iNOS) and nitrotyrosine. Oxidative damage to DNA was investigated by immunostaining for 8-hydroxydeoxyguanosine (8-OHdG), while apoptosis and necrosis were evaluated by in situ ligation with hairpin probes. Myocardial anti-oxidant reserve was evaluated through assessment of superoxide dismutase (SOD1-2) and catalase (CT) activity in two frozen samples from each patient. Results were compared with idiopathic DCM and normal controls. Cardiomyocytes were bigger and myocardial fibrosis was more pronounced in CCM than in the DCM cohort. Contraction band necrosis was always detectable only in CCM with sparse lymphocytic infiltrates in three cases. Both iNOS and nitrotyrosine were significantly more expressed in CCM than in DCM. Immunostaining for 8-OHdG, cardiomyocyte apoptosis, and necrosis were significantly increased in CCM compared with controls and DCM. Myocardial SOD1 and CT activity was significantly decreased compared with DCM and controls, and correlated with cell death and severity of left ventricular dysfunction. Oxidative stress is a major mechanism of myocardial damage in human CCM. It concurs with calcium overload to myocyte dysfunction and death.

Reactive nodular fibrous pseudotumor involving the gastrointestinal tract and mesentery: A case report and review of the literature.

Reactive nodular fibrous pseudotumor (RNFP) is a tumor-like lesion that is characterized by reactive fibroblast/myofibroblast proliferation within collagenic hyalinized stroma, due to its association with injury or inflammation. The current study describes the case of a 60-year-old female with a history of abdominal surgery and abdominal pain. Upon laparoscopy, multiple nodules attached to the outer layer of the colon and mesentery were identified, and therefore, complete surgical excision was performed. Macroscopically, the nodules were well-circumscribed, firm, tan-white in color and ranged in size between 2.0–10.0 cm at the greatest dimension. Microscopically, the nodules were composed of spindle and stellate cells in a dense collagenic hyalinized background with sparse lymphocytic infiltration. Immunohistochemical analysis demonstrated positive staining for vimentin, smooth muscle actin and cluster of differentiation (CD) 117, and focally-positive keratin staining with AE1/AE3; however, no staining was observed for gastrointestinal stromal tumor 1, CD34, S-100, anaplastic lymphoma kinase or β-catenin. Therefore, it was proposed that the lesion may be most accurately described as an RNFP. The current study reports a rare case of RNFP, emphasizing its histopathological features and differential diagnoses to promote an improved and broader understanding of this poorly understood condition.

A Case of Secondary Erythromelalgia With Unusual Histological Findings

Erythromelalgia clinically presents with episodic burning, erythema, and warmth of acral sites. It can be divided into primary and secondary associated with myeloproliferative and autoimmune conditions. Histology commonly shows capillary proliferation, swelling of endothelial cells, perivascular edema, and chronic inflammation with sparse lymphocytic infiltrate. We report a case of a 55-year-old man with classical secondary erythromelalgia clinically; however, he had unusual histological findings on biopsy comprising of acute perivascular infiltrate and perivascular mucin. This is the first report of such findings in the context of secondary erythromelalgia.

Dermatosis papulosa nigra: a case report

A 36-year-old female presented with multiple dark brown papules on the chest and abdomen for more than 10 years,which had gradually increased in number.Physical examination revealed dozens of dark brown,flat papules measuring 1-3 mm in diameter in the chest and abdomen.Most of the lesions had a smooth surface,and some lesions gave a papilloma-like appearance,with no confluent trend.Biopsy of abdominal lesions showed mild hyperkeratosis of epidermis,acanthosis,extension of epidermal protrusions forming a reticulated appearance,horn pseudocysts in prickle cell layer,enhanced pigmentation of basal layer,and a sparse lymphocytic perivascular infiltrate in superficial dermis.A diagnosis of dermatosis papulosa nigra (DPN) was made.

Subcutaneous sarcoidosis

Subcutaneous sarcoidosis is an uncommon kind of sarcoidosis with undetermined etiology.Immune reaction is regarded as the main pathogenesis.The predominant clinical manifestation is painless nodules in extremities together with systemic diseases,such as bihilar lymphadenopathy.Histopathologically,it is characterized by non-caseating epithelioid grannuloma encapsulated with connective tissue and surrounded by a sparse lymphocytic infiltrate in the subcutaneous tissue and deep dermis.The diagnosis of subcutaneous sarcoidosis can be confirmed by the combination of radiology and biopsy.Topical and systemic corticosteroids are the first-line therapy.Other treatment options include tumor necrosis factor (TNF)-α antagonists,immunosuppressive drugs and photodynamic therapy. Key words: Sarcoidosis; Diagnosis; Therapeutics

Low density of sympathetic nerve fibers relative to substance P-positive nerve fibers in lesional skin of chronic pruritus and prurigo nodularis

In prurigo nodularis (PN), an increase in the density of dermal substance P-positive (SP+) sensory nerve fibers has been demonstrated. In addition, the density of sympathetic nerve fibers is unchanged. We aimed to investigate the density and balance of sensory and sympathetic dermal nerves in pruritus on normally appearing skin in comparison to PN. In a parallel investigation in lesional and non-lesional skin routine histological and immunofluorescence staining against SP and tyrosine hydroxylase (TH) were performed. We found an increased density of dermal SP+ nerve fibers in PN and also in pruritus relative to sympathetic nerve fibers in affected areas compared to the unaffected site. The density of SP+ and TH+ nerves did not correlate with clinical parameters such as itch quality, duration or intensity. Sparse lymphocytic infiltration as found in affected pruritus skin may be a source of nerve growth factor and explain the hyperinnervation. Similar to the situation in PN, chronic pruritus lesions also demonstrate a preponderance of SP+ sensory nerve fibers relative to sympathetic nerve fibers, which probably acts as a causal pro-inflammatory signal in development of pruritus. These findings suggest new therapeutic approaches in patients with chronic pruritus.

65-jähriger Patient mit gelb-orange farbenen Papeln an beiden Unterarmen

A 65-year-old man presented with disseminated yellow-orange soft painless papules on both forearms. They had developed over the past five weeks. Clinical and laboratory investigations revealed secondary hyperlipidemia and diabetes mellitus Type 2a. Histology revealed dermal xanthomas consisting of foam cells, giant cells, and a sparse lymphocytic infiltrate. The patient was treated with a low fat, sugar free diet, as well as bezafibrate and metformin. The xanthomas resolved over six months.

Volar Melanotic Macules in a Gardener: A Case Report and Review of the Literature

Volar melanotic macules are asymptomatic, tan-brown to brownish-black macules found on the palms, fingers, soles, and/or toes of dark-skinned individuals and are infrequently reported in light-skinned individuals. Herein, we report the acquisition of multiple, brownish-black volar digital macules in a 63-year-old white woman and avid gardener that were noted after the onset of pruritic, chronic hand dermatitis over a 10-month period. She was healthy without any medical conditions or medications. No family history of intestinal polyposis or mucosal melanosis existed. At presentation, she had less than 20 brownish-black, 2- to 10-mm irregular macules over the volar aspect of the thumbs and index fingers, left greater than right hand, associated with erythema, scale, and a negative potassium hydroxide examination. In addition, she had melanotic macules of her lips, buccal mucosa, and conjuctiva. No nail or anogenital macules were found. Biopsy demonstrated a region of epidermal hyperplasia, hyperkeratosis, and interface dermatitis associated with melanophages and sparse lymphocytic infiltrate. Melanin staining revealed diffuse pan-epidermal hypermelanization, dermal melanin, and dendritic melanocytes, which expressed HMB-45. After 1-year follow-up and treatment with topical corticosteroid, the volar macules have faded to tan brown. Based on the location, avocation, and coexisting mucosal melanotic macules, an irritant phytodermatitis with postinflammatory hyperpigmentation was diagnosed in the setting of Laugier-Hunziker syndrome-a disorder denoted by macular hyperpigmentation of nail, volar, and/or mucosal surfaces in healthy adults. Volar melanotic macules can also complicate 5-flourouracil therapy, tinea pedis, and other inflammatory disorders; be associated with acral melanomas; or represent a cutaneous manifestation of systemic disease such as Addison disease, Peutz-Jegher syndrome, Leopard syndrome, Carney syndrome, AIDS, and neurofibromatosis.

Primary invasive melanoma and basal cell carcinoma (collision tumor) with blue nevus‐like cutaneous metastases

The simultaneous presence of two disparate neoplasms occurring in the same specimen has been well documented, albeit uncommonly. The juxtaposition of malignant melanoma and basal cell carcinoma (BCC) has been rarely reported in case reports, with most cases describing melanoma in situ and BCC. We present two cases of invasive melanoma (Clark level IV, no microscopic satellites present) intimately associated with BCC, and in areas distinction of the two lesions was difficult. Immunohistochemical studies delineated the two cell populations. In addition, one patient presented with multiple cutaneous metastases, all simulating blue nevi. The metastases occurred in the same anatomical region as the primary tumor, and histologically consisted of pigmented dendritic melanocytes and melanophages in the superficial and mid-dermis and arranged in a blue nevus-like lesion. Histologic clues suggesting the possibility of a metastatic melanoma included a sparse lymphocytic infiltrate, the presence of an epithelioid component and atypia of the dendritic melanocytes. However, without appropriate clinical history, the lesions could be overlooked as ordinary blue nevus. Collision tumors containing invasive melanoma and BCC are rare and this is the first report of a collision tumor with blue nevus-like metastasis. Awareness of this phenomenon and pattern of metastasis, together with the clinical findings will aid in the correct classification of these lesions.

Photodermatitis with Minimal Inflammatory Infiltrate

Dermatoses associated with cutaneous photosensitivity are a group of photodistributed skin eruptions caused or exacerbated by light. Multiple clinical variants of photosensitive dermatoses have been characterized including polymorphous light eruption, chronic actinic dermatitis, solar urticaria, phototoxic and photoallergic dermatitis, reticular erythematous mucinosis, acute cutaneous lupus erythematosus, and dermatomyositis. As there may be significant overlap among the clinical presentation of these conditions, the specific diagnosis of individual photodermatosis relies heavily on characteristic histopathologic features. We present here 5 cases of photodistributed eruptions with virtual absence of histologic epidermal changes and dermal inflammation, yet all were described clinically as being "inflammatory" and erythematous. All cases of this "pauci-inflammatory photodermatitis" presented with photodistributed bright red macular erythema or slightly indurated plaques that developed over a period of weeks to months and clinically resembled photoallergic or phototoxic drug reactions or polymorphous light eruption. Microscopically, however, only very sparse dermal lymphocytic infiltrate was noted with no or minimal epidermal changes. To our knowledge, the observation of clinically evident photodistributed dermatoses that demonstrate such minimal histopathologic findings has not been reported. Clinicians and histologists should be aware of the disparity that may be encountered in this setting, as the clinical features are usually far more impressive than those seen histologically.

Prognostic significance of histological features and biological parameters in stage I (pT1 and pT2) colorectal adenocarcinoma

Patients with stage I colorectal cancer have a good prognosis, however, a small fraction of them die of local or distant recurrence after curative resection. The aggressive behavior reflects some biological properties of these tumors. In this study, we evaluated the prognostic role of some histopathological and biological parameters in stage I colorectal carcinomas. From the Colorectal Cancer Registry of Modena, we selected two series of patients; the first included all patients who had died of disease progression, the second included patients with a favorable outcome. The histopathological parameters assessed were grade of differentiation, growth pattern at the invasive tumor front, peritumoral lymphocytic infiltration, tumor budding and vascular invasion. The biological variables were proliferative activity (using Ki-67 nuclear antigen), overexpression of p53 protein and altered expression of the mismatch repair proteins (MLH1 and MSH2). The results showed that an infiltrating growth pattern, absent or sparse peritumoral lymphocytic infiltration, the presence of tumor budding and vascular invasion are significantly related to the risk of recurrence. Among the biological parameters, p53 overexpression was significantly correlated with a poor clinical outcome. Our study showed that the histopathologial features are relevant prognostic indicators and might be used as markers for an appropriate treatment strategy in patients with stage I carcinomas.

Treatment of Recalcitrant Dermatomyositis with Efalizumab

Dermatomyositis (DM) is an auto-immune disease that primarily affects muscles and skin. Muscle weakness appears in the shoulders and hips in particular. Skin symp-toms include a diffuse violaceous erythema and oedema, predominantly of the upper face including the orbita, and violaceous-red papules of the finger (Gottron papules). The pathogenesis of DM is unclear, but recent studies suggest a central role of auto-aggressive lymphocytes and type I interferons (1–4), as has been proposed earlier for cutaneous lupus erythematosus (5–7). Corticosteroids are the established first-line treatment for DM. However, their use is limited because of side-effects. Unfortunately, recalcitrant courses exist that respond poorly to corticosteroids and to other immuno-modulatory and immunosuppressive drugs (8). CASe RepORTAn 82-year-old woman presented with peri-orbital viola-ceous-red oedema and erythema extending to the chest with proximal muscle weakness (Fig. 1a). She suffered from dysphagia and 6 kg weight loss during the last 4 months. Histology of lesional skin biopsy, taken from the chest, revealed an interface dermatitis associated with sparse lymphocytic infiltration in a perivascular distribution and mucin depositions. electromyographic investigations confirmed a pathological reaction pattern in the biceps brachii muscle, indicating myositis. Muscle biopsy was denied. She had slightly elevated antinuclear antibodies (1:80, granular pattern), but blood count, liver enzymes, and serum creatinine kinase were within normal limits. No malignancy could be found.Initial treatment with 60 mg prednisolone per day did not improve the clinical picture. Additional intravenous administration of 15 mg methotrexate per week for 8 weeks also had no effect.This prompted us to initiate a subcutaneous treatment with efalizumab (Raptiva