Adjunctive and Transformed Immunity: Histiocytic & Dendritic Cell Neoplasm

Analysis and Attributes

Follicular dendritic cell sarcoma (FDCS) is a preponderantly adult disease with a median emergence at

44 years) [1]. Localized lesions (FDCS) progress mildly, with a mean survival of roughly 168 months (varying from 2 to 360 months). Limited reoccurrences and remote metastasis are proportionately at 27% and 28% respectively. Enhanced tumour expanse (> 6cm), the appearance of coagulative necrosis, a raised mitosis (> 5/10 hpf) and cytological aberrations may elucidate an inferior prognosis [7]. Tumour Stage may not influence the disease outcome. A two year survival for the preliminary or progressive, localized and distant metastasis is documented at 84.2%, 80% and 42.8% respective [1]. The neoplasm (FDCS) emerges as a gradual tumefaction, commonly situated in the head and neck or the abdominal lymph nodes. A limited cervical or an intra- abdominal swelling may appear in half the (50%) instances. The implicated extra-nodal sites are the Hepatic, Pulmonary, Tonsils and the Spleen [1]. The malignancy (FDCS) may be investigated with the contrast Computerized Tomography(CT) scans extending from the neck to the pelvis in order to assess adjunctive disease. Complete blood counts, bone marrow aspiration and biopsy are recommended. Concomitant viral evaluation such as Human Immune Deficiency Virus (HIV), Epstein Barr Virus (EBV) and Hepatitis assay may be accomplished [1]. Core needle biopsy or an Excision biopsy may be adopted for a precise identification of the tumefaction. Fine needle aspiration cytology (FNAC) may be circumvented.

Histopathology

The tumour specimen is composed of spindle to ovoid cells which may configure fascicles, whorls, diffuse sheets and cellular aggregates. Singular cells elucidate an indeterminate cellular outline and a moderate, non- discernible cytoplasm [Figures 1-9]. Nuclear pseudo- inclusions frequently appear along with bi-nucleation/ multi-nucleation of the tumour cells [3]. Electron microscopy depicts cytoplasmic prolongations and desmosomal intersections. Birbeck granules and plentiful liposomes may not be expressed [6]. Lympho-plasmacytic influx may emerge in majority (90%) of the instances [1] Reed Sternberg like cells may infrequently incite a misinterpretation of a Hodgkin’s Lymphoma. Immune- histochemistry is an advantageous technique to distinguish the tumour (FDCS) from the adjunct Histiocytic neoplasm. Follicular dendritic cell sarcoma is immune reactive to CD21, CD23, CD35, R4/23, Ki -FDC1p and Ki M4 with a variable quantification of CD68 [6]. Cluster in appears as a highly reactive molecule in the neoplasm (FDCS) and may be negative or weakly reactive in the complementary dendritic cell tumours [7, 8, 9, 10, 11, 12]. Desmoplakin. Vimentin, Fascin, Epidermal Growth Factor

Receptor (EGFR), CD45 and HLA-DR may be reactive [6]. Immunoglobulin and T cell receptor genes may be in a germ line disposition. Cytogenetic evaluation of the particular dendritic neoplasm (FDCS) is insufficient and may not benefit the interpretation [1].

Therapeutics

Surgical excision is the preferred modality. The majority (94%) of the patients with limited disease are treated with preliminary surgery [9]. Adjuvant therapy for excised localized lesions is controversial, though radiotherapy and chemotherapy may be employed. Concomitant Chemotherapy and Radiotherapy may benefit the protracted disease. Treatment regimens employed are cyclophosphamide/ vincristine/ doxorubicine, prednisone (CHOP), ifosamide, carbaplatin, etoposide(ICE) and doxorubicin/ bleomycin/ vincristine/ dacarbazine (ABVD), the therapies applicable to infiltrative lymphoma [4, 5, 6]. Cognitive lymphoma chemotherapy is recommended for diffuse follicular dendritic cell sarcoma (FDCS). The province of allogeneic bone marrow transplantation is indeterminate.

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Histopathology

The nodal sinuses are dilated with the mononuclear or multinuclear Langerhans cells admixed with a varying quantity of eosinophils. Focal necrosis with abutting eosinophils is frequent and may be restricted to the sinuses. The nodal configuration may be conserved or partially effaced. Specific organs exhibiting the disorder are the bone, lymph node, pulmonary, thymus, skin, central nervous system (CNS), gastric, hepatic, anus, female genital tract and the thyroid, especially in the Solitary form of Langerhans cell histiocytosis (LCH) [2]. Rosai Dorfman’s disease, parasitic infections, Kimura’s disease, Hypersensitivity reactions, Cat scratch disease , Erdheim –Chester disease, specific Malignant lymphoma, Hodgkin’s Lymphoma and Peripheral T cell lymphoma are the conditions which require a segregation from Langerhans cell histiocytosis [2]. Langerhans cell histiocytosis (LCH) is a disorder of obscure aetiology. A viral origin has not been proved. A disorder with the tumour cells depicting the ultra-structure and immune reactions of Langerhans cells has been described. It is designated as a Langerhans cell sarcoma, analogous to the inter digitating reticulum cell sarcoma and may be a malignant neoplasm of the accessory immune system cells [2].

Histiocytic Sarcoma: Morphology

Histiocytic Sarcoma (HS) is an infrequent, non langerhans cell disorder constituted of mature tissue histiocytes. Of obscure aetiology, the condition may concur with mediastinal germ cell tumour, implying that the Histiocytic Sarcoma (HS) may emerge from the pleuri- potent germ cells [1]. Follicular lymphoma, Myelo- dysplastic syndrome (MDS) and acute lymphoblastic lymphoma (ALL) may be concomitant with the Histiocytic Sarcoma (HS). A Trans –differentiation amidst the Histiocytic Sarcoma (HS) and Follicular Lymphoma cell clones along with the t (14:18) gene translocation and immunoglobulin heavy (Ig H) gene rearrangements, implicates an analogous commencement of the disorders. As chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL) demonstrate clone specific immunoglobulin rearrangements, it is postulated that Histiocytic Sarcoma may develop [1]. Histopathology and Immune-histochemistry are essential in order to distinguish the condition. Immune reactivity for CD 163, CD 68 and lysozyme is exemplified.

Analysis and Attributes

An adult, male preponderance is noted (median presentation at 46-55 years), though no age is exempt. Solitary or multitudinous extra-nodal tumours are described, frequently in the gastro-intestinal tract, skin or soft tissues [1]. Disseminated lymph- node enlargement and manifold tumour loci may be exceptionally elucidated, with a poor prognosis. Fever, weight loss and compression of a vital structure (such as a small bowel obstruction) may descry systemic manifestations. Skin rash is exhibited at numerous sites with dermal lesions [3]. Haematological cytopenias may occur in one-third (30%) instances. A comprehensive staging with computerized tomography (CT) scans and a bone marrow aspiration and biopsy is mandated with solitary lesions which may exhibit a superior prognosis. Excision biopsy is the selected mode of investigation.

Histopathology

Enormous, propagating and dispersed cells twice the diameter of small lymphocytes may appear in concurrence with foci of spindle cell proliferation [1]. Vacuoles are demonstrated in the eosinophilic cytoplasm. Pleomorphic, eccentric nuclei may exhibit single or multiple nucleoli. A xanthomatous manifestation may ensue [3]. Histiocytic markers may be reactive such as CD163, CD 68 and lysozyme. CD 33 is usually non- reactive. S-100 protein may be weak or focally reactive. Ki 67 is variably depicted [1].

Therapeutics

Simple surgical excision or in combination with adjuvant radiotherapy or a surgical resection concomitant with adjuvant chemotherapy is the desirable mode of medication. Multi-various treatment options incorporated for a solitary, extra-nodal tumefaction remains to be evaluated. Cyclophosphamide/ vincristine/ doxorubicine, predinosone (CHOP) is a frequently employed regimen [1]. Adjuvant radiation therapy may diminish the on-site reoccurrences. Adjuvant chemotherapy may benefit the disseminated disease.

Analysis and Attributes

Inter-digitating cell sarcoma (IDCS) is an exceptional neoplasm. The tumour may usually be detected at 56.5 years (detection may extend from 21 months to 88years). The male to female proportion is 1.38:1. The clinical course fluctuates from a benign to an accelerated, fatal condition with dissemination. Instances of intra- abdominal participation and young patients with aggressive disease enunciate a poorer prognosis. Confined, limited lesions elucidate a 1 and 2 year continuance of 84.8% and 68.1% while the diffuse disorder depicts a 1 and 2 year survival of 38.5% and 15.8 % respectively [1]. A solitary lymph node tumefaction is frequent though the adjoining skin and soft tissue may be implicated [13]. Asymptomatic individuals may be elucidated although fatigue, fever and night sweats may ensue. The tumour staging incorporates a contrasting computerized tomography (CT) scan, extending from the neck to the pelvis for a comprehensive assessment. Complete blood counts, bone marrow aspiration and biopsy may be mandated. A viral aetiology has not been implied for the inter-digitating cell sarcoma (IDCS). Thus evaluation for Human immune deficiency virus (HIV) and an exhaustive Hepatitis spectrum is not a pre-requisite. Core needle biopsy or a selective Excision biopsy is required for the identification of the neoplasm. Fine needle aspiration cytology (FNAC) may be averted.

Histopathology

Classically, huge spindle to ovoid cells configuring whorls may be identified. The cells demonstrate a coarse nuclear chromatin with moderate to abundant cytoplasm and may simulate histiocytes. Small lymphocytes commingling with the enormous histiocytic cells is the essential attribute, although it is absent in carcinomas or sarcomas. Immune phenotype is non-reactive for CD1a with a reactive S100 protein, Vimentin, HLA DR, Fascin and CD45, with a variable CD68 and Lysozyme [1]. B cell marker CD20 and T cell markers CD3 and CD 5 may be non-reactive. Cytokeratin, Myeloperoxidase , CD1a , CD 21, CD 23, CD 30, CD 35, Clusterin, Langerin, CD34 , CD 79a, BCL 2 and BCL 6 may also be non reactive(3,13). Electron Microscopy depicts a lack of Birbeck’s granules. Immunoglobulin and T cell receptor genes appear in a germ line configuration.

Therapeutics

The preliminary treatment for limited disease may be radiotherapy or surgical excision, as it enhances the longevity. Diffuse disease may be managed by chemotherapeutic options such as cyclophosphamide/ vincristine/ doxorubicine, predinosone (CHOP), ifosamide, carbaplatin, etoposide(ICE) and doxorubicin/ bleomycin/ vincristine/ dacarbazine (ABVD) with modifiable outcome [13]. The therapeutic options for the disseminated lesions, however, lack concurrence.

Analysis and Attributes

The intermediate dendritic cell sarcoma (INDCS) usually elucidates solitary or multiple papules, nodules or plaques appearing on the trunk, face, neck and extremities in an indeterminate pattern. A skin biopsy is generally diagnostic. Computerized tomography (CT) scans and bone marrow biopsy may be mandated.

Histopathology

Microscopy exhibits an indiscriminate dermal infiltrate. The cellular component is comprised of cells with irregular nuclear grooves and clefts similar to the langerhans cells [1] the cytoplasm is abundant, pale and eosinophilic. Multinucleated giant cells may be demonstrated along with partial spindling or a dendritic configuration. Birbeck granules and desmosomes are absent on electron microscopy, though inter-digitating cell processes may be detected. Immune phenotypic markers describe the tumour cells to be reactive for s100 protein and CD 1a. Non -reactivity for b cell and t cell markers, CD 30, CD 163 CD21, cd23, CD 35 and langerin. Factor xiii a and CD34 may be deficient, in contrast to xantho-granuloma and dermato-fibrosarcoma protuberans respectively [1]. CD45, CD 68, lysozome and CD4 are variably reactive. The human androgen receptor gene assay may be able to clone the intermediate dendritic cell sarcoma (INDCS).

Therapeutics

The tumefaction is gradual and indolent. Recent, fresh lesions may ensue with autonomous retrogression of the tumour. Surgical resection is the preferred treatment modality. Outcomes with chemotherapy and radiotherapy may be unreliable, particularly with diffuse disease. Multiple therapeutic options may be contemplated [1].

Analysis and Attributes

A male predilection and a median age of emergence at 61 years is exhibited. Cervical and mediastinal lymph nodes are frequently implicated. Extra nodal tumours are situated at the hepatic, spleen, renal, adrenal, bone and soft tissue sub-sites [1]. Patients with higher stage disease Aggressive tumours demonstrate a diminished survival. Limited disease elucidates a 2 year continuance at 85.7 % while with the disseminated disease the 2 year median life expectancy was 15 months [1]. A recent, asymptomatic tumefaction is perceived which may be surgically removed. Multitudinous, expanded lymph nodes may be evaluated by a Computerized Tomography (CT) scans and a bone marrow biopsy. The value of these procedures in a solitary nodal incrimination is indeterminate. Excision biopsy is the selective mode of detection [1].

Histopathology

Spindle to ovoid cells articulating whorls in the paracortex, accompanied by abundant, reticulated fibrous tissue may be enunciated. Vimentin, Desmin, Factor XIIIa, Smooth muscle actin are immune –reactive. CD 45RB, CD21, CD35, S-100 protein, CD65 and CD 1a are usually not delineated [1, 3]. Marginal, fusiform , elongated dendritic cytoplasmic projections and desmosomal intercellular junctions may be exhibited on ultra- structure.

Therapeutics

Surgical eradication is preferred for localized lesions. Adjuvant radiotherapy may be of limited value. Adjuvant chemotherapy has a minimal benefit in the controlled disease. Treatment options for disseminated fibroblastic reticular cell tumour (FRCT) have been insufficiently analysed though clinical trials may be a pre-requisite.

Analysis and Attributes

Disseminated juvenile xanthogranuloma (DJX) presents at 10 years of age with one half of the lesions appearing in infancy. Skin, soft tissue with upper airway mucosa is frequent sites of representation. Solitary papules or miniature, multiple lesions may ensue [14]. The central nervous system (CNS), pulmonary, hepatic or ocular sites with lymph nodes and bone marrow may be implicated [1]. Diabetes insipidus, seizures, hydrocephalus and alterations in the mental state may be demonstrated with central nervous system lesions. Excision biopsy of the tumour with appropriate immune histochemical evaluation is recommended. Staging computerized tomography (CT) scans and bone marrow biopsy persist as indeterminate options.

Histopathology

The xanthogranulomatous (JXG) component is comprised of a miniature, round to ovoid cell with a bland, uniform nucleus and stained cytoplasm. Touton giant cells are elucidated at the dermal sites, though infrequent in the non dermal locations. Xanthomatous and inflammatory elements may be exhibited. [1, 3]. Vimentin, Lysozyme, CD14, CD68, CD 163, Stabilin -1 and co-factor XIIIa may be immune-reactive. CD1a and S 100 protein are usually non-reactive though S-100 may be weakly or focally positive [1]. Immunoglobulin G and T cell receptor genes may configure in a germline manner. A multifocal appearance may resemble a lymphoma [15].

Therapeutics

Cutaneous, subcutaneous and soft tissue juvenile xanthogranuloma (JXG) may not require intervention as the lesion automatically regresses. A central nervous system (CNS) or a symptomatic lesion may require additional evaluation and adjuvant chemotherapy. Treatment regimens with vincristine, prednisone and methotrexate may be employed though the patients or the nodules of langerhans cell histiocytosis may demonstrate an inconstant outcome. Additional evaluation in the form of clinical trials may be beneficial [Table 1, 2].