Lymphocytes and sinus histiocytosis in tumor and matched lymph nodes as predictors of survival in non-small-cell lung cancer.

Aim: To analyze immune cell populations in non-small-cell lung cancer (NSCLC) tumors and matched tumor-bearing and non-tumor-bearing lymph nodes (ntbLNs) to predict prognosis. Patients & methods: 71 patients with long-term disease-free survival and 80 patients with relapse within 3 years were included in this study. We used Cox regression to identify factors associated with overall survival (OS) and progression-free survival (PFS). Results: Sinus histiocytosis and tumor-infiltrating lymphocyte density in the tumor were positively associated with PFS and OS. CD4 expression in node 1 (hazard ratio = 0.72; p = 0.02) and node 2 (hazard ratio = 0.91; p = 0.04) ntbLNs were positively correlated with OS and PFS, respectively. Discussion: Immunological markers in ntbLNs could be used to predict survival in NSCLC.

Lay abstract Aim: We analyzed populations of immune cells in non-small-cell lung cancer (NSCLC). In addition, we also investigated lymph nodes from the same patient that contained or did not contain cancer cells. Patients & methods: We included 71 patients whose cancer did not return within 3 years and 80 patients whose cancer did return within 3 years after they underwent surgery to remove their tumors. We used various statistical methods to identify factors that can predict survival. Results: Sinus histiocytosis (a widening of ducts in the lymph nodes due to an increased number of certain cells) and the density of tumor-infiltrating lymphocytes (immune cells that enter the tumor to destroy it) can predict how long patients can survive after surgery or if their tumor will come back quickly. Discussion: Looking at immune cells can help physicians decide which patients need increased follow-up care due to an increased risk for their tumors to return.

Rosai-Dorfman disease with infiltration of IgG4-bearing plasma cells presenting as laryngeal-nasal masses and cervical lymphadenopathy: A case report.

RATIONALE: Rosai-Dorfman disease (RDD) is a rare and self-limiting condition caused by the non-neoplastic proliferation of histiocytes/phagocytes in the sinusoids of lymph nodes and in extranodal tissues. Of the extranodal involvement, laryngeal involvement is extremely rare. Because of its rarity and nonspecific clinicoradiologic features, RDD is often difficult to differentiate from other benign or malignant lymphoproliferative diseases. We present a case of RDD with infiltration of IgG4-bearing plasma cells manifesting laryngeal and nasal masses with cervical lymphadenopathy. PATIENT CONCERNS: A 45-year-old male patient presented with recurrent epistaxis and airway disturbance. DIAGNOSES: On endoscopy, there were submucosal masses in both nasal cavities and both sides of subglottic larynx. On neck CT, there were well-defined, enhancing soft tissue masses in both nasal cavities and both sides of subglottic larynx, resulting in mild airway narrowing. In addition, multiple enlarged lymph nodes showing homogeneous enhancement were noted in both parotid glands and both internal jugular chains. All lesions demonstrated marked FDG-uptake on PET/CT. Therefore, the initial radiologic differential diagnoses included lymphoma and IgG4-related disease. Biopsy was performed on the nasal and laryngeal lesions, and they revealed RDD with infiltration of IgG4-bearing plasma cells. INTERVENTION: The patient underwent surgical resection of the masses in the nasal cavity and larynx to relieve airway narrowing. OUTCOMES: After surgery, airway obstruction was much improved and the patient was asymptomatic. On outpatient follow-up, he exhibited a stable condition and had no dyspnea on exercise. LESSONS: Clinical awareness and suspicion are important for the accurate diagnosis and management of patients with homogeneous masses in the larynx or nasal cavity, even if there is no combined cervical lymphadenopathy.

Case of Generalized Tumor-Type Rosai-Dorfman Disease With Sarcoidosis-Like Histological Features and IgG4-Positive Plasma Cells.

ABSTRACT: Rosai-Dorfman disease (RDD, also known as sinus histiocytosis with massive lymphadenopathy) is a rare and benign non-Langerhans cell histiocytosis. Skin biopsy usually shows nodular or diffuse dermatitis. Rosai-Dorfman cells (RDD cells) and emperipolesis are the key to diagnosis. RDD cells express S-100 antigen, CD68, CD163, α1-antitrypsin, α1-antichymotrypsin, and ham-56, whereas Langerhans cell markers such as CD1a and langerin are negative. We presented a case of a 55-year-old man with varying sizes of many dark red nodules and lumps over the face, trunk, and limbs for approximately 1 year but without systemic involvement. The results of the laboratory evaluations were notable for an increased level of serum IL-6 and serum IgG4. Histopathological examination showed a diffused dense nodular infiltration of "nude" epithelioid histiocytes with infiltration of minimal lymphocytes and plasm cells around the epithelioid nodules. Immunohistochemistry identified nodular histiocytes being stained strongly positive for S-100 and CD68 but negative for CD1a. Plasma cells showed focally positive for IgG, IgG4, and CD38 and with a ratio of IgG4/IgG >40%. Considering these findings, we believe that our case meets the diagnostic description of "cutaneous Rosai-Dorfman disease" and is, therefore, a rare case with clinical features of multiple tumor-like nodules, sarcoidosis-like histological features, and immunohistochemistry of IgG4-positive plasma cells.

Cutaneous Rosai - Dorfman disease in a patient with late syphilis and cervical cancer - case report and a review of literature.

BACKGROUND: Cutaneous Rosai - Dorfman disease (CRDD) is extremely rare variant of idiopathic histiocytic proliferative disorder, which may manifest as a non-specific macules, papules, plaques or nodules ranging in size and colour from yellow - red to red -brown. CASE PRESENTATION: A 52-year-old female presented with three gradually enlarging, reddish - brown nodules on the right upper extremity lasting six months. The patients denied fever, weight loss, malaise. Clinical examination and imaging tests showed no sign of lymphadenopathy. A biopsy specimen of a nodule showed a dense dermal polymorphic infiltrate with numerous histiocytes exhibiting emperipolesis phenomenon. Immunohistochemical staining of the histiocytes showed S-100 protein (+), CD68(+), but CD1a (-). Aforementioned findings were consistent with CRDD characteristics. Additionally, a routine serological screening and confirmatory serological tests for syphilis were positive. Syphilis of unknown duration was diagnosed. The IgG antibodies titre against Chlamydia trachomatis was elevated. An isolated sensory impairment over the right trigeminal nerve was found on neurological consultation. Comprehensive gynaecological assessment was carried out because of patient's complaints of bleeding after sexual intercourse and led to diagnosis of cervical cancer. The initial therapy with methotrexate was discontinued after three months due to neutropenia. Further therapy with dapson was ineffective, therefore complete surgical excision was recommended. CONCLUSIONS: CRDD is a rare, benign condition especially difficult to diagnose due to lack of general symptoms and lymphadenopathy. Histopathologic examination with immunohistochemical staining, exhibiting characteristic and reproducible findings play a key role in establishing an accurate diagnosis. In the presented case activated histiocytes demonstrated in a lesional skin might be a response to immune dysregulation related to chronic, untreated sexually transmitted infections and cancer.

Rosai-Dorfman Disease of the Breast With Variable IgG4+ Plasma Cells: A Diagnostic Mimicker of Other Malignant and Reactive Entities.

Rosai-Dorfman disease (RDD) is an uncommon disorder, characterized by an atypical expansion of histiocytes which classically shows emperipolesis and immunoreactivity with S-100 protein. RDD affects the lymph nodes as well as extranodal sites; however, RDD of the breast is exceptionally rare. Herein, we describe the histopathologic features of 22 cases of RDD occurring in the breast, with an emphasis on the differential diagnosis. All cases were notable for an exuberant lymphocytic infiltrate with and without germinal center formation, and the majority (19/22) showed numerous plasma cells: 5 to 132/high-power field (HPF). IgG and IgG4 immunohistochemical stains were available for 13 cases; in no instance were criteria for IgG4-related sclerosing disease met, though in a single case the IgG4/IgG ratio was increased to 25%. Sclerosis was present in the majority of cases (18/22), and was frequently prominent. RDD cells showing emperipolesis were present in all cases (22/22), and ranged from rare (<1/50 HPF) to numerous (>50/50 HPF). Two of the cases in our series were initially misdiagnosed as inflammatory myofibroblastic tumor and plasma cell mastitis with granulomatous inflammation. As emperipolesis can be indistinct, the presence of stromal fibrosis and a prominent lymphoplasmacytic inflammatory infiltrate should prompt a careful search for the characteristic histiocytes, which can be aided by the use of S-100 immunohistochemistry.

The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus.

OBJECTIVES: Clinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life. METHODS AND RESULTS: By harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain-of-function p.G13C KRAS mutation, in a boy with the seemingly unrelated immune dysregulatory conditions of Rosai-Dorfman and systemic lupus erythematosus (SLE). CONCLUSIONS: This case expands our understanding of the clinical phenotypes associated with the extremely rare condition of RALD, and emphasizes the importance of always considering the possibility of a monogenic cause for autoimmunity, particularly when the disease manifestations begin early in life and do not follow a typical clinical course.

[Expression of IgG4 in Rosai-Dorfman disease and its significance].

OBJECTIVE: To study the prevalence of IgG4-positive plasma cells in Rosai-Dorfman disease and to assess the association between Rosai-Dorfman disease and IgG4-related sclerosing disease (IgG4-SD). METHODS: The clinicopathologic features of 12 tissue samples of Rosai-Dorfman disease (11 extranodal and one nodal) from nine patients were reviewed. The degree of fibrosis and occlusive phlebitis was studied by HE staining. The expression of IgG4 and IgG in plasma cells were studied by immunohistochemistry (EnVision) and quantitatively analyzed by medical image analysis system. RESULTS: Nine tissue samples showed different degree of fibrosis (four tissue samples were mild, one tissue sample was moderate and four tissue samples were severe) and two tissue samples showed occlusive phlebitis in the lesional tissue. Immunohistochemical study showed marked infiltration by IgG4-positive plasma cells (> 50 per high-power field) in four tissue samples, moderate infiltration (30 to 50 per high-power field) in two tissue samples, mild (10 to 29 per high-power field) in three cases and negative infiltration (< 10 per high-power field) in three tissue samples (P < 0.01). Three tissue samples fulfilled the diagnostic criteria of IgG4-SD (> 50 IgG4-positive plasma cells per high-power field and IgG4-to-IgG ratio > 40%), including one tissue sample each of Rosai-Dorfman disease in the left facial skin, above the left eye socket, and in the right parotid. CONCLUSIONS: Some cases of Rosai-Dorfman disease fulfill the diagnostic criteria and show the histologic features of IgG4-SD. They may represent members of the IgG4-SD spectrum. The detection of IgG4-positive plasma cells in the lesional tissues of Rosai-Dorfman disease may have clinical pathological significance.

Primary cutaneous marginal IgG4 lymphoma and Rosai-Dorfman's disease coexisting in several lesions of the same patient.

We report the unique association of primary cutaneous marginal zone B-cell lymphoma and Rosai-Dorfman disease (RDD)-type histiocytic infiltrates involving the same lesions. The patient was an 82-year-old woman with 3 long-standing, well-circumscribed firm erythematous to brownish plaques on her left arm, right scapular area, and lumbosacral area. Histopathologic examination disclosed a dermal and subcutaneous nodular lymphoplasmacytic infiltrate with evidence of germinal center colonization and light-chain restriction and sheets of S-100 CD68-positive histiocytes with ample pale cytoplasm and occasional emperipolesis of lymphocytes. The neoplastic plasma cells expressed immunoglobulin (Ig) G4. A review of 14 examples of cutaneous RDD showed a substantial number of IgG4-positive cells in only 3 of them, and a review of 8 primary cutaneous marginal zone B-cell lymphomas disclosed only 2 with significant IgG4 expression. The coexistence of lymphomas and RDD has been rarely reported in the literature but only seldom involving the same lymph node and-to the best of our knowledge-never in the skin.

Dural-based Rosai-Dorfman disease: differential diagnostic considerations.

Extranodal sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a non-neoplastic condition that has rarely been reported to involve the central nervous system. This report documents a 28-year-old man with Rosai-Dorfman disease who presented with a seizure and a dural-based mass that was thought to represent a meningioma. Resection showed a lesion marked by large, S-100 protein immunoreactive histiocytic cells with intermixed benign lymphocytes and plasma cells. Emperipolesis with intracytoplasmic lymphocytes and plasma cells was present. Differential diagnostic considerations will be discussed.

No increase in IgG4-positive plasma cells in limbal Rosai-Dorfman disease.

PURPOSE: Extranodal Rosai-Dorfman disease is a rare benign condition recently reported to sometimes show features of IgG4-related disease. The purpose of this study was to describe the corneal-limbal manifestation of the entity and to investigate whether numerous IgG4-positive plasma cells are associated with the disease at this site. METHODS: This is an interventional retrospective small case series. RESULTS: Two patients presenting with painless limbal mass lesions underwent total excisional biopsy with anterior lamellar keratoplasty for diagnostic and therapeutic purposes. Histopathologic evaluation of the specimens revealed inflammatory lesions containing atypical S100-immunoreactive histiocytes diagnostic of Rosai-Dorfman disease, but not an increase in the IgG4-positive plasma cells. Point mutations (V600E) in the BRAF oncogene were absent. CONCLUSIONS: Rosai-Dorfmann disease should be considered in the differential diagnosis of limbal mass lesions. Involvement at this site was not associated with BRAF mutation or IgG4 abnormalities in the cases examined.

Possible association of cutaneous Rosai-Dorfman disease and chronic Crohn disease: a case series report.

IMPORTANCE Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman disease limited to the skin, has a wide range of clinical presentations. Rosai-Dorfman disease is believed to result from an aberrant response to antigens, caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is also implicated in the pathogenesis of Crohn disease, linking these otherwise unrelated entities. To our knowledge, the coexistence of these disorders has been described in only 2 cases, 1 of them confined to the skin and soft tissue. OBSERVATIONS We present a series of 3 patients who developed purely CRDD in the context of long-standing Crohn disease. Statistical estimates suggested that the association of these 2 disorders is not due to chance (P<.001). CONCLUSIONS AND RELEVANCE Our case series provides the clinical correlate to the pathogenetic parallels between CRDD and Crohn disease. Crohn disease is frequently complicated by various skin manifestations, which may be mimicked by CRDD. Therefore, it may be prudent for clinicians to include CRDD in the list of differential diagnoses when examining skin lesions in patients with Crohn disease.