IMAGES IN CYTOLOGY Section Editor: Stephan Pambuccian, M.D.
Rosai–Dorfman Disease Unusual Presentation and Diagnosis by Fine-Needle Aspiration Cytology Jai Kumar Chaurasia, M.D.,1* Geetika Singh, M.D.,1 Biswajit Sahoo, M.D.,2 and Veena Maheshwari, M.D.1
Rosai–Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare non-neoplastic, selflimiting histiocytic proliferative disorder of unknown etiology that usually presents with painless bilateral cervical lymphadenopathy and show distinct cytological features.1 Retroperitoneal lymph node enlargement due to RDD is unusual and is rarely reported in literature. It is a difficult diagnosis due to disease’s non-specific clinical, hematological, and radiological findings, often overlapping with other diseases. We report an unusual case of RDD in a 55-year-old male patient who presented with diffuse abdominal pain and retroperitoneal lymphadenopathy and diagnosed on fine-needle aspiration cytology (FNAC). A 55-year-old man presented with the complaint of fever, malaise, fatigue, and diffuse abdominal pain. On clinical examination no cervical, axillary, and inguinal lymphadenopathy or organomegaly was appreciated. Routine hematological investigations revealed anemia (9.5 g/ dl Hb), total leucocyte count (18,500/mm3) with polymorphonuclear leucocytosis. Erythrocyte sedimentation rate (ESR) was raised (55 mm/hour). Computed tomography 1 Department of Pathology, Jawaharlal Nehru Medical College (JNMC), Aligarh Muslim University (AMU), Aligarh, Uttar Pradesh, India 2 Department of Radiodiagnosis, Jawaharlal Nehru Medical College (JNMC), Aligarh Muslim University (AMU), Aligarh, Uttar Pradesh, India. *Correspondence to: Dr. Jai Kumar Chaurasia, M.D., Department of Pathology, Jawaharlal Nehru medical College (JNMC), Aligarh Muslim, University (AMU), Aligarh, Uttar Pradesh, India. E-mail: [email protected] Conflict of interest: Nothing to report Received 26 March 2014; Revised 26 August 2014; Accepted 8 October 2014 DOI: 10.1002/dc.23232 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
C 2014 WILEY PERIODICALS, INC. V
(CT) scan of patient’s abdomen revealed multiple enlarged, discrete retroperitoneal lymphnodes in paraaortic, mesenteric, interaortocaval, paracaval regions (Fig. 1). The largest retroperitoneal lymph node measured 3 cm 3 2 cm. No other masses were noted. CT guided FNAC of paraaortic lymphnode was performed through retroperitoneal approach followed by ultrasound guided FNAC of mesenteric lymphnodes. The smears were prepared from paraaortic and mesenteric nodes and were stained with Papanicolaou (PAP) stain and Hematoxylin and Eosin stain (H&E). Microscopic examination revealed hypercellular smear having inflammatory infiltrate comprising of numerous large histiocytes, lymphocytes, some plasma cells, and few polymorphs (Fig. 2). The histiocytes showed abundant cytoplasm, rounded nuclei with smooth nuclear membranes, fine chromatin, and distinct single or multiple prominent nucleoli (Figs. 3 and 4). Multinucleated histiocytes were also appreciated (Fig. 3). The histiocytes showed prominent “emperipolesis” of intact lymphocytes and plasma cells (Figs. 3 and 4). Further, optimal cell blocks were prepared. Immunostaining of cell blocks revealed positive CD-68 and S-100 immunoexpression in histiocytes (Fig. 5). CD 1a, T-cell markers CD-3, CD-5, B-cell markers CD-19, CD-20, and pancytokeratin immunomarkers were found to be negative. Based on FNAC findings, the patient was diagnosed as having RDD. The patient was kept on corticosteroid therapy and during the past 6 months of patient’s followup, retroperitoneal lymphnodes gradually regressed and then disappeared. The diagnosis of RDD is difficult as patients often present with non-specific clinical symptoms including fever, malaise, fatigue, and abdominal pain. Moreover, laboratory investigative findings are not pathognomic and radiological features are also wide and non-specific.2 Diagnostic Cytopathology, Vol. 00, No 00
1
Diagnostic Cytopathology DOI 10.1002/dc
CHAURASIA ET AL.
Fig. 3. High magnification, showing prominent “emperipolesis” by a large multinucleated histiocyte (Papanicolaou 5003).
Fig. 1. Contrast enhanced CT scan showing multiple enlarged retroperitoneal lymph nodes.
Fig. 4. Showing prominent “emperipolesis” by a large single nucleated histiocyte (H&E 5003).
Fig. 2. FNAC smear from paraaortic lymphnode showing inflammatory infiltrate comprising of multiple large histiocytes, lymphocytes, some plasma cells. Histiocytes show “emperipolesis” (arrow) (Papanicolaou 503).
FNAC is regarded as the initial investigation for enlarged lymph nodes as it is simple, easy, quick, and inexpensive. Though the diagnosis of RDD is established on histological changes in the affected lymph node, but frequently the diagnosis can be made on FNAC which reveals disease’s distinct cytological features. FNAC in RDD shows numerous histiocytes with abundant cytoplasm, fine granular nuclei, and “emperipolesis” characterized by engulfment of intact lymphocytes, plasma 2
Diagnostic Cytopathology, Vol. 00, No 00
cells, and RBCs by large histiocytes, which is the hallmark of the disease. The cytomorphological differential diagnosis of RDD in the present case include other histiocytic disorders such as hemophagocytic lymphohistiocytosis, xanthogranulomatous lymphadenitis, reactive sinus histiocytosis and langerhans cell histiocytosis, histiocyte rich lymphomas, and tuberculosis. Hemophagocytic lymphohistiocytosis is a hematologic disorder and shows phagocytosis of hemopoietic cells by the histiocytes. Also, clinically it presents with hepatospenomegaly and pancytopenia in contrast to the present case.3 Cytomorphologically, xanthogranulomatous lymphadenitis consists of foamy histiocytes with vacuolated cytoplasm and lacks “emperipolesis.”4 Similarly,
Diagnostic Cytopathology DOI 10.1002/dc
ROSAI-DORFMAN DISEASE: UNUSUAL PRESENTATION
Fig. 5. (a, b) Cell block immunostaining showing intense CD-68 and S-100 positivity of histiocytes, respectively.
langerhans cell histiocytosis (LCH) can be distinguished cytomorphologically as it shows numerous atypical CD1a positive histiocytes having characteristic intranuclear pseudoinclusions, prominent nuclear indentations, and grooves in a background of polymorphous inflammation comprising of eosinophils, neutrophils, and lymphocytes.5 Though, histiocyte rich lymphomas show reactive lymphocytes and histiocytes, neoplastic lymphoma cells showing positive T or B cell immunoexpression are always present and were thus differentiated from RDD in the present case.6 Reactive sinus histiocytosis shows numerous histiocytes but it lacks “emperipolesis.” Tuberculosis show characteristic epithelioid histiocytes and caseous necrosis and thus was excluded. In majority of cases, RDD has an indolent and selflimiting course and clinical observation without treatment is advisable. Surgery is only indicated in cases of vital organ compression.7 The use of corticosteroid has also been advocated.8 The patient in the present case responded to corticosteroid therapy with regression and finally disappearance of lymphadenopathy, thus avoiding excisional biopsy, aggressive intervention, and overtreatment. This case report emphasizes that RDD should always be considered in cases presenting with retroperitoneal lymphadenopathy and FNAC can be used as a reliable tool to establish the diagnosis, avoiding
unnecessary excisional biopsy, aggressive intervention, and overtreatment.
References 1. Park YK, Kim YW, Choi WS, Lim YJ. Sinus histiocytosis with massive lymphadenopathy. Multiple skull involvements. J Korean Med Sci 1998;13:423–427. 2. La Barge DV, III, Salzman KL, Harnsberger HR, et al. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman Disease): Imaging manifestations in the head and neck. AJR 2008;191: 299–306. 3. Schettert IT, Cardinalli IA, Ozello MC, Vassallo J, Lorand-Metze I, de Souza CA. Hemophagocytic syndrome: Pitfalls in its diagnosis. Sao Paulo Med J 1997;115:1548–1552. 4. Cozzutto C, Soave F. Xanthogranulomatous lymphadenitis. Virchows Arch A Pathol Anat Histol 1979;385:103–108. 5. Lee JS, Lee MC, Park CS and Juhng SW. Fine needle aspiration cytology of Langerhans cell histiocytosis confined to lymph nodes. A case report. Acta Cytol 1997;41:1793–1796. 6. Rajwanshi A, Banerjee AK, Chawla YK. T cell rich and histiocyte rich B cell lymphoma—A case report. Indian J Pathol Microbiol 1997;40:85–89. 7. Pulsoni A, Anghel G, Falcucci P, et al. Treatment of sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease): Report of a case and literature review. Am J Hematol 2002;69:67– 71. 8. Raveenthiran V, Dhanalakshmi M, Hayavadana Rao PV, Viswanathan P. Rosai–Dorfman disease: Report of a 3-year old girl with critical review of treatment options. Eur J Pediatr Surg 2003; 13:350–354.
Diagnostic Cytopathology, Vol. 00, No 00
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Rosai–Dorfman Disease Unusual Presentation and Diagnosis by Fine-Needle Aspiration Cytology Jai Kumar Chaurasia, M.D.,1* Geetika Singh, M.D.,1 Biswajit Sahoo, M.D.,2 and Veena Maheshwari, M.D.1
Rosai–Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare non-neoplastic, selflimiting histiocytic proliferative disorder of unknown etiology that usually presents with painless bilateral cervical lymphadenopathy and show distinct cytological features.1 Retroperitoneal lymph node enlargement due to RDD is unusual and is rarely reported in literature. It is a difficult diagnosis due to disease’s non-specific clinical, hematological, and radiological findings, often overlapping with other diseases. We report an unusual case of RDD in a 55-year-old male patient who presented with diffuse abdominal pain and retroperitoneal lymphadenopathy and diagnosed on fine-needle aspiration cytology (FNAC). A 55-year-old man presented with the complaint of fever, malaise, fatigue, and diffuse abdominal pain. On clinical examination no cervical, axillary, and inguinal lymphadenopathy or organomegaly was appreciated. Routine hematological investigations revealed anemia (9.5 g/ dl Hb), total leucocyte count (18,500/mm3) with polymorphonuclear leucocytosis. Erythrocyte sedimentation rate (ESR) was raised (55 mm/hour). Computed tomography 1 Department of Pathology, Jawaharlal Nehru Medical College (JNMC), Aligarh Muslim University (AMU), Aligarh, Uttar Pradesh, India 2 Department of Radiodiagnosis, Jawaharlal Nehru Medical College (JNMC), Aligarh Muslim University (AMU), Aligarh, Uttar Pradesh, India. *Correspondence to: Dr. Jai Kumar Chaurasia, M.D., Department of Pathology, Jawaharlal Nehru medical College (JNMC), Aligarh Muslim, University (AMU), Aligarh, Uttar Pradesh, India. E-mail: [email protected] Conflict of interest: Nothing to report Received 26 March 2014; Revised 26 August 2014; Accepted 8 October 2014 DOI: 10.1002/dc.23232 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
C 2014 WILEY PERIODICALS, INC. V
(CT) scan of patient’s abdomen revealed multiple enlarged, discrete retroperitoneal lymphnodes in paraaortic, mesenteric, interaortocaval, paracaval regions (Fig. 1). The largest retroperitoneal lymph node measured 3 cm 3 2 cm. No other masses were noted. CT guided FNAC of paraaortic lymphnode was performed through retroperitoneal approach followed by ultrasound guided FNAC of mesenteric lymphnodes. The smears were prepared from paraaortic and mesenteric nodes and were stained with Papanicolaou (PAP) stain and Hematoxylin and Eosin stain (H&E). Microscopic examination revealed hypercellular smear having inflammatory infiltrate comprising of numerous large histiocytes, lymphocytes, some plasma cells, and few polymorphs (Fig. 2). The histiocytes showed abundant cytoplasm, rounded nuclei with smooth nuclear membranes, fine chromatin, and distinct single or multiple prominent nucleoli (Figs. 3 and 4). Multinucleated histiocytes were also appreciated (Fig. 3). The histiocytes showed prominent “emperipolesis” of intact lymphocytes and plasma cells (Figs. 3 and 4). Further, optimal cell blocks were prepared. Immunostaining of cell blocks revealed positive CD-68 and S-100 immunoexpression in histiocytes (Fig. 5). CD 1a, T-cell markers CD-3, CD-5, B-cell markers CD-19, CD-20, and pancytokeratin immunomarkers were found to be negative. Based on FNAC findings, the patient was diagnosed as having RDD. The patient was kept on corticosteroid therapy and during the past 6 months of patient’s followup, retroperitoneal lymphnodes gradually regressed and then disappeared. The diagnosis of RDD is difficult as patients often present with non-specific clinical symptoms including fever, malaise, fatigue, and abdominal pain. Moreover, laboratory investigative findings are not pathognomic and radiological features are also wide and non-specific.2 Diagnostic Cytopathology, Vol. 00, No 00
1
Diagnostic Cytopathology DOI 10.1002/dc
CHAURASIA ET AL.
Fig. 3. High magnification, showing prominent “emperipolesis” by a large multinucleated histiocyte (Papanicolaou 5003).
Fig. 1. Contrast enhanced CT scan showing multiple enlarged retroperitoneal lymph nodes.
Fig. 4. Showing prominent “emperipolesis” by a large single nucleated histiocyte (H&E 5003).
Fig. 2. FNAC smear from paraaortic lymphnode showing inflammatory infiltrate comprising of multiple large histiocytes, lymphocytes, some plasma cells. Histiocytes show “emperipolesis” (arrow) (Papanicolaou 503).
FNAC is regarded as the initial investigation for enlarged lymph nodes as it is simple, easy, quick, and inexpensive. Though the diagnosis of RDD is established on histological changes in the affected lymph node, but frequently the diagnosis can be made on FNAC which reveals disease’s distinct cytological features. FNAC in RDD shows numerous histiocytes with abundant cytoplasm, fine granular nuclei, and “emperipolesis” characterized by engulfment of intact lymphocytes, plasma 2
Diagnostic Cytopathology, Vol. 00, No 00
cells, and RBCs by large histiocytes, which is the hallmark of the disease. The cytomorphological differential diagnosis of RDD in the present case include other histiocytic disorders such as hemophagocytic lymphohistiocytosis, xanthogranulomatous lymphadenitis, reactive sinus histiocytosis and langerhans cell histiocytosis, histiocyte rich lymphomas, and tuberculosis. Hemophagocytic lymphohistiocytosis is a hematologic disorder and shows phagocytosis of hemopoietic cells by the histiocytes. Also, clinically it presents with hepatospenomegaly and pancytopenia in contrast to the present case.3 Cytomorphologically, xanthogranulomatous lymphadenitis consists of foamy histiocytes with vacuolated cytoplasm and lacks “emperipolesis.”4 Similarly,
Diagnostic Cytopathology DOI 10.1002/dc
ROSAI-DORFMAN DISEASE: UNUSUAL PRESENTATION
Fig. 5. (a, b) Cell block immunostaining showing intense CD-68 and S-100 positivity of histiocytes, respectively.
langerhans cell histiocytosis (LCH) can be distinguished cytomorphologically as it shows numerous atypical CD1a positive histiocytes having characteristic intranuclear pseudoinclusions, prominent nuclear indentations, and grooves in a background of polymorphous inflammation comprising of eosinophils, neutrophils, and lymphocytes.5 Though, histiocyte rich lymphomas show reactive lymphocytes and histiocytes, neoplastic lymphoma cells showing positive T or B cell immunoexpression are always present and were thus differentiated from RDD in the present case.6 Reactive sinus histiocytosis shows numerous histiocytes but it lacks “emperipolesis.” Tuberculosis show characteristic epithelioid histiocytes and caseous necrosis and thus was excluded. In majority of cases, RDD has an indolent and selflimiting course and clinical observation without treatment is advisable. Surgery is only indicated in cases of vital organ compression.7 The use of corticosteroid has also been advocated.8 The patient in the present case responded to corticosteroid therapy with regression and finally disappearance of lymphadenopathy, thus avoiding excisional biopsy, aggressive intervention, and overtreatment. This case report emphasizes that RDD should always be considered in cases presenting with retroperitoneal lymphadenopathy and FNAC can be used as a reliable tool to establish the diagnosis, avoiding
unnecessary excisional biopsy, aggressive intervention, and overtreatment.
References 1. Park YK, Kim YW, Choi WS, Lim YJ. Sinus histiocytosis with massive lymphadenopathy. Multiple skull involvements. J Korean Med Sci 1998;13:423–427. 2. La Barge DV, III, Salzman KL, Harnsberger HR, et al. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman Disease): Imaging manifestations in the head and neck. AJR 2008;191: 299–306. 3. Schettert IT, Cardinalli IA, Ozello MC, Vassallo J, Lorand-Metze I, de Souza CA. Hemophagocytic syndrome: Pitfalls in its diagnosis. Sao Paulo Med J 1997;115:1548–1552. 4. Cozzutto C, Soave F. Xanthogranulomatous lymphadenitis. Virchows Arch A Pathol Anat Histol 1979;385:103–108. 5. Lee JS, Lee MC, Park CS and Juhng SW. Fine needle aspiration cytology of Langerhans cell histiocytosis confined to lymph nodes. A case report. Acta Cytol 1997;41:1793–1796. 6. Rajwanshi A, Banerjee AK, Chawla YK. T cell rich and histiocyte rich B cell lymphoma—A case report. Indian J Pathol Microbiol 1997;40:85–89. 7. Pulsoni A, Anghel G, Falcucci P, et al. Treatment of sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease): Report of a case and literature review. Am J Hematol 2002;69:67– 71. 8. Raveenthiran V, Dhanalakshmi M, Hayavadana Rao PV, Viswanathan P. Rosai–Dorfman disease: Report of a 3-year old girl with critical review of treatment options. Eur J Pediatr Surg 2003; 13:350–354.
Diagnostic Cytopathology, Vol. 00, No 00
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