In histopathology, a palisade is a single layer of relatively long cells, arranged loosely perpendicular to a surface and parallel to each other. [1] A rosette is a palisade in a halo or spoke-and-wheel arrangement, surrounding a central core or hub. [2] A pseudorosette is a perivascular radial arrangement of neoplastic cells around a small blood vessel. [2] Rosettes are characteristic of tumors.
A rosette is a cell formation in a halo or spoke-and-wheel arrangement, surrounding a central core or hub. The central hub may consist of an empty-appearing lumen or a space filled with cytoplasmic processes. The cytoplasm of each of the cells in the rosette is often wedge-shaped with the apex directed toward the central core: the nuclei of the cells participating in the rosette are peripherally positioned and form a ring or halo around the hub. [2]
Rosettes may be considered primary or secondary manifestations of tumor architecture. Primary rosettes form as a characteristic growth pattern of a given tumor type whereas secondary rosettes result from the influence of external factors on tumor growth. For example, regressive cell swelling may centripetally displace the cytoplasm as the nucleus is squeezed to the periphery, forming a secondary rosette. Although the presence of primary rosettes may suggest a given diagnosis, usually this finding alone is not considered absolutely pathognomonic for one specific tumor type. [2]
Loss or gain of genetic information is the main cause of rosette and pseudorosette formation. The cell populations exhibiting neuronal differentiation are believed to secrete surface glycoproteins and glycolipids which mediate cell-to-cell recognition and adhesion. One hypothesis is that these sticky cell surface markers cause the developing cell bodies to cluster or aggregate and their primitive neurites to tangle. As the cells grow, the neurite tangle remains centrally located and the cell bodies are squeezed to the periphery, thus explaining the rosette pattern. Depending upon their location, ependymal cells may display 2 cell poles. A luminal pole projects to the ependymal lining of a ventricle and a "submesenchymal pole" projects toward the surface of the brain demonstrating glial processes and peripherally situated footplates. Frieda and Pollak conceptualize the architecture of ependymomas as a primitive neural tube turned inside out with the submesenchymal poles converging toward a central vessel, thus forming a pseudorosette rather than projecting centrifugally toward the pia. [2]
True rosettes are mainly found in neuropathologic disorder. Other conditions where they are present include osteosarcoma, non-Hodgkin lymphoma, fibromyxoid sarcoma, medullary thyroid carcinoma, embryonal tumor with abundant neuropil and true rosettes (ETANTR), rhabdomyosarcoma, chronic cholestasis and chronic active hepatitis, tobacco rosette: complex viral disease, malaria, adenocarcinoma in colon and rectum, hyalinizing spindle cell fused with giant rosette, and endometrial stromal sarcoma with hyalinizing giant rosettes. [2]
Flexner–Wintersteiner rosettes, a spoke-and-wheel shaped cell formation seen in retinoblastoma and certain other ophthalmic tumors, [3] ) have been described as a form of palisading. [4]
Unlike the center of the Homer-Wright rosette, the central lumen is devoid of fiber-rich neuropil. The defining feature of this rosette is the central extension of cytoplasmic projections of the surrounding cells. Like the Homer Wright rosette, the Flexner–Wintersteiner rosette represents a specific form of tumor differentiation. [5] [6] [7] [8] Electron microscopy reveals that the tumor cells forming the Flexner–Wintersteiner rosette have ultrastructural features of primitive photoreceptor cells. [9] Furthermore, the rosette lumen shows similar staining patterns as in rods and cones, [10] suggesting that Flexner–Wintersteiner rosettes represent a specific form of retinal differentiation. In addition to being a characteristic finding in retinoblastomas, Flexner–Wintersteiner rosettes may also be found in pinealoblastomas and medulloepitheliomas. [5]
Flexner–Wintersteiner rosettes were first described in 1891 by Simon Flexner, a professor of experimental pathology at the University of Pennsylvania. Flexner noted characteristic clusters of cells in an infantile eye tumor which he called retinoepithelioma. [11] [12] [13] In 1897, Austrian ophthalmologist Hugo Wintersteiner confirmed Flexner's observations and noted that the cell clusters resembled rods and cones. [14] These characteristic rosette formations were subsequently recognized as important features of retinoblastomas.
A pseudorosette is a perivascular radial arrangement of neoplastic cells around a small blood vessel. Pseudorosettes are present in neuroblastoma, medulloblastoma, malignant melanoma, ependymoma, Merkel cell carcinoma, neuroendocrine tumor of the skin, seborrheic keratosis, dendritic cell neurofibroma, astroblastoma, large cell neuroendocrine tumor of the cervix, clear cell ependymoma of the spinal cord, celiac disease, nasal tumor of olfactory origin, rosette-forming glioneural tumor (RGNT), oncocytoma, Wilm's tumor, and pheochromocytoma of the urinary bladder. [2]
A Homer-Wright pseudorosette is a type of pseudorosette in which differentiated tumor cells surround the neuropil. [15] Examples of tumors containing these are neuroblastoma, medulloblastoma, pinealoblastoma, and primitive neuroectodermal tumors of bone. Homer-Wright rosettes are considered "pseudo" in the sense that they are not true rosettes. Unlike Flexner–Wintersteiner rosettes, which contain an empty lumen, Homer-Wright rosettes contain abundant fibrillary material. They are named for James Homer Wright.
A perivascular pseudorosette consists of a spoke-wheel arrangement of cells with tapered cellular processes radiates around a wall of a centrally placed vessel. The modifier “pseudo” differentiates this pattern from the Homer Wright and Flexner-Wintersteiner rosettes, perhaps because the central structure is not actually formed by the tumor itself, but instead represents a native, non-neoplastic element. Also, some early investigators argued about the definition of a central lumen, choosing “pseudo” to indicate that the hub was not a true lumen but contained structures. Nevertheless, this pattern remains extremely diagnostically useful and the modifier unnecessarily leads to confusion. Perivascular pseudorosettes are encountered in most ependymomas regardless of grade or variant. As such, they are significantly more sensitive for the diagnosis of ependymomas than true ependymal rosettes. Unfortunately, perivascular pseudorosettes are also less specific in that they are also encountered in medulloblastomas, PNETs, central neurocytomas, and less often in glioblastomas, and a rare pediatric tumor, monomorphous pilomyxoid astrocytomas. [2]
Histologic features of these two tumors are virtually identical, including their tendency to form neuropil-rich rosettes, referred to as pineocytomatous/neurocytic rosettes in central neurocytoma. Both are quite similar to the Homer-Wright rosette, but they are generally larger and more irregular in contour. The cells of the pineocytomatous/neurocytic rosettes are also considered to be much more differentiated than the cells forming Homer-Wright rosettes in that the nuclei are slightly larger, more rounded, much less mitotically active, and paler or less hyperchromatic. In rare cases, these rosettes may aggregate in a sheet of back-to-back clusters resembling fieldstone pavement. [2]
The neuropathologic diagnosis of brain tumors entails the microscopic examination of conventional formalin-fixed paraffin-embedded tissue samples surgically removed from a radiographically defined lesion. Pathologists rely on visual clues such as pattern recognition when examining the stained tissue with a microscope, much as radiologists rely on grayscale patterns of densities and intensities on images. Some histologic patterns of cellular architecture are distinctive if not pathognomonic whereas others are less specific, but nevertheless considerably narrow the differential diagnosis. The precise biologic bases for some of the observed microscopic patterns are poorly understood though their recognition is nonetheless useful. Rosettes are a commonly encountered neuropathologic histologic architectural pattern seen within certain tumors is the rosette. Although more advanced methods of tissue examination have been developed, such as histochemical and immunohistochemical profiling, genetic analysis, and electron microscopy, the microscopic review of H&E stained material remains a critical component of tumor diagnosis. [2]
Immunohistochemical evidence of neuronal differentiation is found in nearly all cases with neuronal markers such as synaptophysin, neuronspecific enolase, and neurofilament protein. Some medulloblastomas may also display other forms of differentiation as demonstrated by the presence of the astrocytic marker glial fibrillary acidic protein. Skeletal muscle and melanocytic differentiation are considerably less common and define the medullomyoblastoma and melanotic medulloblastoma variants, respectively. [2]
Palisades that are generally longer than a rosette or pseudorosette can be seen in neural tumors such as Schwannoma, [16] [17] as well as in ameloblastomas. They can also be seen in nodular basal-cell carcinomas. [18]
Pseudopalisading, a visually similar finding, is the formation of hypercellular zones that typically surrounds necrotic tissue.
An ependymoma is a tumor that arises from the ependyma, a tissue of the central nervous system. Usually, in pediatric cases the location is intracranial, while in adults it is spinal. The common location of intracranial ependymomas is the fourth ventricle. Rarely, ependymomas can occur in the pelvic cavity.
A blastoma is a type of cancer, more common in children, that is caused by malignancies in precursor cells, often called blasts. Examples are nephroblastoma, medulloblastoma, and retinoblastoma. The suffix -blastoma is used to imply a tumor of primitive, incompletely differentiated cells, e.g., chondroblastoma is composed of cells resembling the precursor of chondrocytes.
In pathology, grading is a measure of the cell appearance in tumors and other neoplasms. Some pathology grading systems apply only to malignant neoplasms (cancer); others apply also to benign neoplasms. The neoplastic grading is a measure of cell anaplasia in the sampled tumor and is based on the resemblance of the tumor to the tissue of origin. Grading in cancer is distinguished from staging, which is a measure of the extent to which the cancer has spread.
The Gleason grading system is used to help evaluate the prognosis of men with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts prognosis and helps guide therapy. A Gleason score is given to prostate cancer based upon its microscopic appearance.
Medulloblastoma is a common type of primary brain cancer in children. It originates in the part of the brain that is towards the back and the bottom, on the floor of the skull, in the cerebellum, or posterior fossa.
A ganglioglioma is a rare, slow-growing primary central nervous system (CNS) tumor which most frequently occurs in the temporal lobes of children and young adults. They are mixed cell tumors containing both neural ganglionic cells and neural glial cell components.
Primitive neuroectodermal tumor is a malignant (cancerous) neural crest tumor. It is a rare tumor, usually occurring in children and young adults under 25 years of age. The overall 5 year survival rate is about 53%.
Sebaceous carcinoma, also known as sebaceous gland carcinoma (SGc), sebaceous cell carcinoma, and meibomian gland carcinoma, is an uncommon malignant cutaneous (skin) tumor. Most are typically about 1.4 cm at presentation. SGc originates from sebaceous glands in the skin and, therefore, may originate anywhere in the body where these glands are found. SGc can be divided into 2 types: periocular and extraocular. The periocular region is rich in sebaceous glands making it a common site of origin. The cause of these lesions in the vast majority of cases is unknown. Occasional cases may be associated with Muir-Torre syndrome. SGc accounts for approximately 0.7% of all skin cancers, and the incidence of SGc is highest in Caucasian, Asian, and Indian populations. Due to the rarity of this tumor and variability in clinical and histological presentation, SGc is often misdiagnosed as an inflammatory condition or a more common neoplasm. SGc is commonly treated with wide local excision or Mohs micrographic surgery, and the relative survival rates at 5 and 10 years are 92.72 and 86.98%, respectively.
Juxtaglomerular cell tumor is an extremely rare kidney tumour of the juxtaglomerular cells, with fewer than 100 cases reported in literature. This tumor typically secretes renin, hence the former name of reninoma. It often causes severe hypertension that is difficult to control, in adults and children, although among causes of secondary hypertension it is rare. It develops most commonly in young adults, but can be diagnosed much later in life. It is generally considered benign, but its malignant potential is uncertain.
Pineoblastoma is a malignant tumor of the pineal gland. A pineoblastoma is a supratentorial midline primitive neuroectodermal tumor. Pineoblastoma can present at any age, but is most common in young children. They account for 0.001% of all primary CNS neoplasms.
The WHOclassification of tumours of the central nervous system is a World Health Organization Blue Book that defines, describes and classifies tumours of the central nervous system (CNS).
A subependymoma is a type of brain tumor; specifically, it is a rare form of ependymal tumor. They are usually in middle aged people. Earlier, they were called subependymal astrocytomas.
Medulloepithelioma is a rare, primitive, fast-growing brain tumour thought to stem from cells of the embryonic medullary cavity. Tumours originating in the ciliary body of the eye are referred to as embryonal medulloepitheliomas, or diktyomas.
Flexner is a surname. Notable people with the surname include:
Pediatric ependymomas are similar in nature to the adult form of ependymoma in that they are thought to arise from radial glial cells lining the ventricular system. However, they differ from adult ependymomas in which genes and chromosomes are most often affected, the region of the brain they are most frequently found in, and the prognosis of the patients. Children with certain hereditary diseases, such as neurofibromatosis type II (NF2), have been found to be more frequently afflicted with this class of tumors, but a firm genetic link remains to be established. Symptoms associated with the development of pediatric ependymomas are varied, much like symptoms for a number of other pediatric brain tumors including vomiting, headache, irritability, lethargy, and changes in gait. Although younger children and children with invasive tumor types generally experience less favorable outcomes, total removal of the tumors is the most conspicuous prognostic factor for both survival and relapse.
NUT carcinoma is a rare genetically defined, very aggressive squamous cell epithelial cancer that usually arises in the midline of the body and is characterized by a chromosomal rearrangement in the nuclear protein in testis gene. In approximately 75% of cases, the coding sequence of NUTM1 in band 14 on the long arm of chromosome 15 is fused to BRD4 or BRD3, which creates a chimeric gene that encodes the BRD-NUT fusion protein. The remaining cases, the fusion of NUTM1 is to an unknown partner gene, usually called NUT-variant.
Papillary tumors of the pineal region were first described by A. Jouvet et al. in 2003 and were introduced in the World Health Organization (WHO) classification of central nervous system in 2007. Papillary Tumors of the Pineal Region are located on the pineal gland which is located in the center of the brain. The pineal gland is located on roof of the diencephalon. It is a cone-shaped structure dorsal to the midbrain tectum. The tumor appears to be derived from the specialized ependymal cells of the subcommissural organ. Papillary tumors of the central nervous system and particularly of the pineal region are very rare and so diagnosing them is extremely difficult.
A central nervous system primitive neuroectodermal tumor, often abbreviated as PNET, supratentorial PNET, or CNS-PNET, is one of the 3 types of embryonal central nervous system tumors. It is considered an embryonal tumor because it arises from cells partially differentiated or still undifferentiated from birth. Those cells are usually neuroepithelial cells, stem cells destined to turn into glia or neurons. It can occur anywhere within the spinal cord and cerebrum and can have multiple sites of origins, with a high probability of metastasis through cerebrospinal fluid (CSF).
The histopathology of colorectal cancer of the adenocarcinoma type involves analysis of tissue taken from a biopsy or surgery. A pathology report contains a description of the microscopical characteristics of the tumor tissue, including both tumor cells and how the tumor invades into healthy tissues and finally if the tumor appears to be completely removed. The most common form of colon cancer is adenocarcinoma, constituting between 95% and 98% of all cases of colorectal cancer. Other, rarer types include lymphoma, adenosquamous and squamous cell carcinoma. Some subtypes have been found to be more aggressive.
Embryonal tumor with multilayered rosettes (ETMR) is an embryonal central nervous system tumor. It is considered an embryonal tumor because it arises from cells partially differentiated or still undifferentiated from birth, usually neuroepithelial cells, stem cells destined to turn into glia or neurons. It can occur anywhere within the brain and can have multiple sites of origins, with a high probability of metastasis through cerebrospinal fluid (CSF). Metastases outside the central nervous system have been reported, but remain rare.