Year : 2010 | Volume
: 53 | Issue : 2 | Page : 244--247
Castleman's disease - hyaline vascular type - clinical, cytological and histological features with review of literature
Arnab Ghosh, Seema V Pradhan, OP Talwar
Department of Pathology, Manipal College of Medical Sciences and Manipal Teaching Hospital, Pokhara, Nepal
Department of Pathology, Manipal Teaching Hospital, Phulbari, Pokhara
Background and Aims: Castleman«SQ»s disease (CD) is a rare disease of lymph node with two identified forms - the hyaline vascular (HV) type or angiofollicular type and plasma cell (PC) type. It usually presents as localized or systemic lymphadenopathy or even as extra nodal mass and may give rise to several differential diagnoses. Fine needle aspiration cytology (FNAC), as the initial investigation, may be misleading. Excision biopsy usually gives the diagnosis. This study analyzes the clinical, cytological and histological features of CD of HV type Materials and Methods: All the cases of CD reported between 2001 and March 2008 have been reviewed. Cytology and histopathology slides of all cases were reviewed by two reporting pathologists independently and the clinical records were analyzed. Result: We had five cases of CD all of which presented as cervical lymphadenopathy of 1 to 5 cms in young patients. Patients were mostly asymptomatic with all relevant investigations within normal limits. The cytology findings mostly showed a predominance of small lymphocytes with capillary fragments. On excision biopsy, all cases were diagnosed as CD of HV type. Conclusion: CD should be kept as a differential of lymphadenopathy, especially in asymptomatic and young patients.
|How to cite this article:|
Ghosh A, Pradhan SV, Talwar O P. Castleman's disease - hyaline vascular type - clinical, cytological and histological features with review of literature.Indian J Pathol Microbiol 2010;53:244-247
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Ghosh A, Pradhan SV, Talwar O P. Castleman's disease - hyaline vascular type - clinical, cytological and histological features with review of literature. Indian J Pathol Microbiol [serial online] 2010 [cited 2020 Jul 6 ];53:244-247
Available from: http://www.ijpmonline.org/text.asp?2010/53/2/244/64335
Castleman's disease (CD) is a rare benign systemic lymphoproliferative disorder that may present as a nodal or extra nodal mass. , Synonyms include angiomatous lymphoid hamartoma, angiofollicular hyperplasia, giant lymph node hyperplasia and follicular lymphoreticuloma.  It represents a morphologically distinct rare form of massive lymph node hyperplasia rather than a neoplasm or hamartoma. , Microscopically, two distinct histological patterns have been described - the hyaline vascular (HV) type or angiofollicular type and plasma cell (PC) type. ,,
Here we present clinical, cytological and histopathological features of five cases of CD of HV type
Materials and Methods
This study was carried out in the Department of Pathology in our hospital during the period of 2001 to March 2008. During this period we had five cases of CD diagnosed by histopathology. All the cases had undergone prior fine needle cytology. All the histopathological and cytology slides were retrieved from the archives of the department and reviewed by two reporting pathologists. In all cases, Leishman stain and Papanicolaou stain were used for cytology slides while the histopathology slides were stained with H and E and reticulin stain. Clinical features and relevant radiological findings were also reviewed and compared.
The relevant clinical findings of all the five cases are summarized in [Table 1]. All the patients presented with complaints of gradually increasing neck mass. One case [Case 3] also complained of simultaneous axillary mass. Only one patient [Case 5] had fever at the time of presentation, none of the patients had any other systemic complaints. Hepatosplenomegaly and abdominal lymphadenopathy were not noted in any of the cases under ultrasonography (USG). Routine investigations including complete blood counts and ESR were within normal limits in all cases. Three out of five cases [Cases 1, 4, 5] had chest x-ray done which did not show any abnormality including mediastinal lymphadenopathy. Case 1 had normal computed tomography (CT) scan of thorax and abdomen. Two cases [cases 1 and 2] had follow-up for six months and one case [case 5] a follow-up for two months. None of these three cases showed any recurrence. Cases 3 and 4 were lost to follow-up.
All the five cases yielded highly cellular material. All the cases showed a polymorphous cell population with predominance of small lymphocytes [Figure 1]. Four out of five cases showed fragments of capillaries with hyalinization [Figure 2]. In only one case, a few singly scattered large oval cells with indistinct margins were seen. These cells had pale cytoplasm with fine chromatin with inconspicuous nucleoli. Intranuclear groove and multinucleation were not noted in any of the cases. Bare nuclei and scattered plasma cells were seen in all cases. All the salient features of the FNAC findings are tabulated in [Table 2].
The gross features of all the five nodes were granular tan cut surface without any area of necrosis or hemorrhage [Figure 3]. Microscopy examination of all the five cases showed the classical features of hyaline vascular type of CD. All the cases showed marked follicular hyperplasia of varying sizes, most with prominent mantle zone [Figure 4] and [Figure 5]. Blood vessels were seen from the capsule to the interior. Most of the follicles showed hyalinized vessels in the center [Figure 5] inset. The interfollicular zone showed numerous postcapillary venules and capillaries along with plasma cells, immunoblasts, histiocytes and also eosinophils. Considering multiple hyalinized vessels in the center of the follicles showing prominent mantle zone, a diagnosis of hyaline vascular type of CD was given in all the cases.
CD was first described by Castleman et al. in 1954 and again in 1956 in a report of cases of solitary masses in the mediastinum. , Later similar cases were reported in other parts of the body which included localized, multicentric, nodal and even extranodal masses.  Most commonly involved sites are mediastinum (60%), retroperitoneum (11%), and axilla (4 %).  It occurs most commonly in adults mostly under 30 years of age but it can also affect children. , In our study, one out of five cases was in adult more than 30 years of age.
Microscopically, as stated above, two distinct histological patterns have been described - the hyaline vascular (HV) type or angiofollicular type and plasma cell (PC) type. However, depending on clinical presentation they can be divided into solitary or localized and multicentric or systemic type. More than 90% of the solitary type is HV type and almost all of the multicentric type is histologically PC type.  However, multicentric HV type has been reported. 
The hyaline vascular variant comprises 90% of CD and mostly presents as a solitary lymphadenopathy - most commonly in mediastinum (60%), but also abdomen, neck, lung, axilla, mesentry, broad ligament, retroperitoneum, soft tissue of the extremities, nasopharynx, leptomeninges, adrenal, paraadrenal and parotid. ,,,,,,, In our study, however, all the five cases presented as cervical lymphadenopathy and only one case had associated axillary lymphadenopathy. Similarly, in the study by Mallik et al. also, all the cases presented as cervical lymphadenopathy.  The size of the lesion varies widely ranging from 1 - 12 cms with a mean diameter of 6 cms.  In our study , the size ranged between 1 to 5 cms. Patients of HV type CD are asymptomatic in more than 50% of cases as also in our study.  However, general signs like fever, asthenia and weight loss may be seen.  We had one case with fever of short duration.
Recognition of CD in cytology smears is often difficult and only a few case reports are available. In the present study the predominant cytology feature was a polymorphous population with predominance of small lymphocyte and many capillary fragments. However, a study by Mallik et al. suggested that the main and most consistent clue to the cytological diagnosis of CD is the presence of large atypical cells with "crumpled tissue paper" like chromatin, occasional multinucleation , nuclear indentations and nuclear grooves. In contrary, in our study, scattered large cells were seen in only one case and these cells showed predominantly fine chromatin - we could not appreciate "crumpled tissue paper like chromatin" in these cells. Also, multinucleation and nuclear grooves were not found. Hidvegi et al. commented that CD may mimic Hodgkin's lymphoma and angioimmunoblastic lymphadenopathy. However, we did not find any cell with prominent nucleolus mimicking Hodgkins cell, in any of our cases, as also commented by Mallik et al. . Moreover, eosinophils were not seen in four cases and only occasionally seen in one case. So, in our study, Hodgkin's lymphoma or any other malignancies were not considered as a differential in the initial cytology diagnosis and also by both the reviewers. Initial cytology impression was reactive hyperplasia similar to other authors.  Predominance of small lymphocytes with increased number of capillary fragments has also been reported by others as the main findings. ,, The large atypical cells are known to be CD 21 positive and categorized as follicular dendritic cell.  In case of presentation as a mediastinal mass, mistaken diagnosis of thymoma is a possibility on image guided FNAC. 
Grossly it is known to be well circumscribed and can measure even 15 cm or more in diameter.  In our study, all the nodes were equal to or less than 5 cms. Cut surface does not show any necrosis as in all the cases in our studies.  Microscopically, the characteristic features are increased number of scattered large follicles, many of which with hyalinization and marked vascular proliferation of their germinal centers. Often capillaries penetrating the follicle give a "lollipop" appearance.  Lymphocyte arrangement in the mantle zone gives a "targetoid" or "stadium seating" or "onion skin" appearance. The interfollicular area shows marked proliferation of postcapillary venules and presence of plasma cells, eosinophils, immunoblasts, and monocytes.  Sinuses are usually not apparent. 
HV type is further subdivided into "lymphoid subtype" with marked mantle zone hyperplasia, and "stroma rich subtype" with prominent vascular and associated myoid component.  The former merges with "mantle zone hyperplasia" and the latter merges with angiomatoid proliferative lesion and angiomatoid hamartomas. ,, Histopathologically, differential diagnosis includes follicular lymphoma , mantle zone lymphoma, AIDS related complex and thymoma. ,
The etiology is unknown. However, the two main hypotheses are viral infection and abnormal reaction.  Recent works indicate possibility of immunologic pathogenesis.  Human herpes virus 8 and interleukin 6 are regarded to be linked to the pathogenesis.  Dysplastic or atypical follicular dendritic cells positive for CD21 and CD35 have frequently been described in the hyalinized center and also in the cytology smears, and can even show monoclonality, yet their role in the pathogenesis is unclear. ,, CD generally follows a benign course and, in most cases, surgical removal of the affected lymph node is curative as re-growth is not expected. ,
Castleman disease should be kept as a differential of localized or multicentric lymphadenopathy especially in asymptomatic and young patients.
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