Henry Ford Hospital Medical Journal

Volume 21 | Number 1 Article 2

3-1973 Malignant Histiocytosis of the Robb-Smith Type (Histiocytic Medullary Reticulosis) Michael F. Macken

Ellis J. Van Slyck

Sheik M. Saeed

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Recommended Citation Macken, Michael F.; Van Slyck, Ellis J.; and Saeed, Sheik M. (1973) "Malignant Histiocytosis of the Robb-Smith Type (Histiocytic Medullary Reticulosis)," Henry Ford Hospital Medical Journal : Vol. 21 : No. 1 , 4-10. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol21/iss1/2

This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Henry Ford Hosp. Med. Journal Vol. 21, No. 1, 1973

Malignant Histiocytosis of the Robb-Smith Type

(Histiocytic Medullary Reticulosis)

Michael F. Macken, MD,* Ellis J. Van Slyck, MD,* and Sheikh M. Saeed, MD**

THE morphologically descriptive term, "histiocytic medullary reticulosis", was proposed by Scott and Robb-Smith^ in 1939 for a clinicopathologically distinct, rapidly fatal disorder found in four patients. The disease was characterized A 60-year-old woman developed high fever, by fever, weight loss, generalized jaundice, anemia with pancytopenia and hepatosplenomegaly. She deteriorated lymphadenopathy, and in the terminal rapidly and died one month later, having stages, severe anemia, jaundice, pan­ shown no beneficial effect from high dose cytopenia and purpura. The pathologi­ corticosteroids and splenectomy. An cal examination revealed systemic pro­ antemortem diagnosis of malignant his­ tiocytosis of the Robb-Smith type was made liferation of histiocytes, some of which and duly confirmed by autopsy study. This demonstrated erythrophagocytosis. rare disorder of the reticuloendothelial system, heretofore designated "histiocytic In this paper we present another case medullary reticulosis," deserves recognition of this rare entity, with a review of the and inclusion among the histiocytic diseases and in the classification of the lymphomas. pertinent clinical and histological fea­ Its proper nosologic designation is sug­ tures. The proper place and designation gested. for this disease in the current classifica­ tion of the diseases of the reticuloen­ dothelial system is offered later in the text and in Table I.

Case Report This 60-year-old housewife was well until August 9, 1969, when she was admitted to another hospital with bilateral flank pain of • Division of Clinical Hematology, Depart­ sudden onset. Examination revealed marked ment of Medicine. bilateral costovertebral angle tenderness and an enlarged spleen, which was palpable two- •'Department of Pathology. finger breadths below the left costal margin. The patient received only analgesics and all Address reprint requests to: Ellis J. Van symptoms subsided within 24 hours. Inves­ Slyck, MD, Henry Ford Hospital, 2799 W. tigation of the genitourinary tract disclosed Grand Blvd., Detroit, Ml 48202 only an incidental reduplication anomaly of Macken, Van Slyck and Saeed

presence of a few shotty lymph nodes in the TABLE 1 posterior cervical, axillary, and inguinal DISORDERS OF THE MALIGNANT regions; an enlarged liver, palpable 4 cms RETICULUM CELL (HISTIOCYTE) below the right costal margin and an enlarged spleen, palpable 8 cms below the 1. Reticulum cell sarcoma group. left costal margin. A) Malignant lymphoma, undifferentiated. 1. Burkitt's lymphoma. Laboratory studies revealed the following: B) Malignant lymphoma, histiocytic hemoglobin 7.9 grams/100 ml and white (Reticulum cell sarcoma). blood count 3,400/cu mm. The differential 0) Malignant histiocytosis. count showed 54% neutrophils, 5% bands, 1. Leukemic reticuloendotheliosis occasional myelocytes and promyelocytes, (Acute monocytic leukemia). 12% monocytes, 25% lymphocytes, 1% 2. Malignant histiocytosis,Robb-Smith eosinophils, and 2% basophils. The type. reticulocyte count was 15.4% and the platelet 2. Hodgkin's disease. count was 77,000/cu mm. The direct and 3. Differentiated progressive histiocytosis. indirect Coombs' tests were negative. The A) Letterer-Siwe disease (in the bilirubin was 4.5 mgs/100 ml with 0.16 histiocytosis X group). mgs/100 direct reacting. Additional studies 4. Mycosis fungoides. gave the following results: serum LDH 2,000 A) Sezary's syndrome. units/IOOml. Prothrombin time 15 seconds with a control of 12 seconds. Partial throm­ boplastin time was 88 seconds with a control of 61 seconds, and fibrinogen was 125 both collecting systems. Because of the mgs/100 ml. Urinary hemosiderin test was unexplained splenomegaly, evaluation of the positive. The fasting blood sugar, BUN, hematopoietic system was done, yielding creatinine electrolytes and serum protein normal results for the following tests: electrophoresis were within normal limits. hemoglobin, hematocrit, bilirubin, urinary Cultures of the urine, blood, sputum and urobilinogen, Coombs'test, heterophile ag­ bone marrow were negative. Right iliac bone glutination, lupus erythematosis preparation, marrow examination showed marked nor­ serum lactic dehydrogenase, protein elec­ moblastic hyperplasia with an M:E ratio of trophoresis, alkaline phosphatase, brom­ 1:1. Occasional abnormal neoplastic histio­ sulphalein retention, blood urea nitrogen, cytes were seen, some of which showed creatinine and calcium. Radiographs of the phagocytosis of erythrocytes, normoblasts, chest and lumbosacral spine were normal. leukocytes and even platelets, (Figure 1). However, her white blood count was 3,100 with a left shift of the neutrophils. Platelets The patient's condition rapidly deterio­ were decreased. The bone marrow showed rated with deepening jaundice and increasing a decreased M:E ratio (1:1) as a result of anemia. Daily afternoon temperature spikes increased erythropoiesis. Diagnosis on dis­ reached 105°F. She was treated with predni­ charge from the hospital was "probable ure­ sone, 60 mgs per day, but showed no teral calculus and hypersplenism of undeter­ improvement. Transfusions with fresh whole mined etiology." blood were given, followed by splenectomy and biopsy of the liver and the periaortic The patient did well for the next three nodes. Following the operation*, the weeks and then developed spiking daily tem­ peripheral blood showed increasing num­ peratures, a seven-pound weight loss and a bers of neoplastic phagocytic reticulum cells feeling of apprehension. Noting icterus, (2-4%) (Figure 2), increased polychromasia, hepatomegaly and further enlargement of spherocytosis, basophilic stippling, Howell- her spleen, her physician referred her to the Jolly bodies, erythroblastosis and a pro­ Hematology Division of the Henry Ford Hos­ nounced granulocytic left shift. The patient pital. continued to do poorly and died 48 hours later. Physical examination now revealed an acutely ill, jaundiced female with blood pres­ sure of 120/80,pulse of 84/minute and temper­ ature of 101°F. Head, eye, ear, nose and throat, cardiopulmonary and genitourinary •Surgical consultation and splenectomy were examinations were within normal limits. The done by Joseph P. Elliott, Jr., MD, General significant physical abnormalities were the Surgery II. Malignant Histiocytosis of the Robb-Smith Type

jf \ Figure 1 Marrow aspirate showing two malignant histiocytes. Note ingested erythrocytes and normo­ blasts. Leishman's stain approximately x2000

r.. Figure 2 Peripheral blood. Lobulated and multinucleated histiocyte with phagocytized erythrocyte. Leishman's stain approximately x2000 Macken, Van Slyck and Saeed

Figure 3 Spleen. Parenchyma is replaced by neoplastic, occasionally multinucleated, reticulum cells some of which show phagocytized erythrocytes (arrows). H & E stain x390

Pathology The right and left lungs weighed 750 and 400 grams respectively. Both lungs were con­ Surgical Specimens: gested. The right lower lobe also showed The spleen was markedly enlarged, areas of consolidation. measuring 27 x 15.5 x 8 cms, and weighed 1700 grams. The consistency was moderately The heart weighed 380 grams and showed firm. Capsule was intact, smooth and dark moderate coronary arteriosclerosis with par­ gray in color. Cut surface of the spleen had tial occlusion of right coronary artery lumen. a purplish cast with punctate areas of gray- Arteriosclerosis of aorta and larger branches white nodularity. A yellow infarcted area was present. occupied the inferior peripheral part of the spleen. The liver weighed 2600 grams. The cut sur­ face was mottled with areas of red-brown The liver biopsy specimen measured 1.0 x and yellowish color. 0.5 X 0.3 cms and had a granular yellow-green color. The abdominal lymph nodes showed marked enlargement, ranging from 3.0 to 8.0 Two enlarged lymph nodes measuring up cm in size. They were located for the most to 1 cm were also submitted and were both part around the aorta below the renal replaced by yellow-gray, soft tumor. arteries and around the pancreas. These nodes had a firm, fleshy consistency with a Cross Autopsy Findings: salmon-pink color. The bone marrow was The body was markedly dehydrated and soft and pale. No nodules were seen. jaundiced. Ecchymoses were obvious over the abdominal wall. The right and left pleural Nothing remarkable was found upon spaces contained respectively 200 ml and 150 examination of other organs including pan­ ml of serosanguinous fluid and 350 ml of creas, genitourinary tract, endocrine organs, serosanguinous fluid were present in the musculo-skeletal system and the central peritoneal cavity. nervous system. Malignant Histiocytosis of the Robb-Smith Type

Figure 4 Abnormal, phagocytic reticulum cells infiltrate the hepatic sinusoids. H & E stain x780

Figure 5 Abdominal lymph node. Overgrowth of reticulum cells is interrupted by benign appearing his­ tiocytes giving "starry-sky" appearance. H & E stain x150 Macken, Van Slyck and Saeed

Figure 6 Bone marrow. Infiltration by phagocytic, benign appearing reticulum cells. H & E stains x780

Histologic Examination: gregates individual cells radiated and infil­ Sections of the spleen revealed almost trated along the hepatic sinuses between cell complete destruction of normal splenic cords, (Figure 4). Modest Kupfer cell hyper­ architecture. Massive proliferation of large, trophy and bile stasis were noted. Tumor tis­ bizarre tumor cells infiltrated the cortex, sue involving the lymph nodes broke medulla, trabeculae, germinal areas and the through the capsule and infiltrated perinodal sinuses, (Figure 3). The tumor cells generally fat. Scattered among the masses of neoplas­ had abundant cytoplasm with large, fre­ tic reticulum cells were large benign histio­ quently lobulated, vesicular nuclei and prom­ cytes giving a "starry-sky" appearance to the inent nucleoli. Binucleate and multi­ lymph nodes, (Figure 5). nucleate giant tumor cells were also seen. Cells in mitosis were frequent. Several of the Autopsy material showed the histologic tumor cells had frothy, irregular cytoplasm pattern of the tumor involving the lymph and phagocytic activity was noted. Within the nodes and liver was similar to the biopsy phagocytic vacuoles karyorrhectic nuclear specimens described above. The character of debris or erythrocyte fragments could be the tumor involving the bone marrow, how­ seen. ever, was considerably different. Among islands of intense erythroid hyperplasia were Sections of the liver and lymph nodes also large clusters of histiocytes with abundant showed histiocytic malignant reticulum cells. cytoplasm and phagocytic vacuoles, but with In the liver, these tumor cells aggregated in reticular nuclei exhibiting minimal the periportal areas, and from these ag­ pleomorphism. The chromatin pattern was Malignant Histiocytosis of the Robb-Smith Type faidy uniform and nucleoli were of modest been demonstrated by a number of size. These histiocytes showed more intense authors.^'-"''Increasing jaun­ erythrophagocytosis than the undif­ ferentiated histiocytic tumor cells in the dice, high serum LDH, urinary other organs, (Figure 6). hemosiderinuria, altered red cell morphology and erythroblastosis all Sections of the lungs showed edema, con­ indicated rapid red cell destruction in gestion and focal bronchopneumonia. The our patient. Marrow erythroid hyper­ heart contained small scars in the left ven­ tricular wall. The kidney sections showed plasia excluded tumor induced bile casts but were otherwise unremarkable. myelosuppression. Rappaport ^° has Changes were inconsequential in other stated that the anemia in MHRS Is prob­ organs including pancreas, genital system, ably due to hypersplenism, but endocrine glands and central nervous cytochemical and ferrokinetic studies system. seem to suggest that it is due in large part to erythrophagocytosis by histio­ Discussion cytes in the bone marrow and reticuloen­ dothelial system generally.Lack of This case typifies the major clinical improvement in the anemia following and histologic features of malignant his­ splenectomy would also speak for a tiocytosis of the Robb-Smith type mechanism different from hyper­ (MHRS). Data from a review of 49 cases splenism. by Creenberg et al^ indicates that An autoimmune component has not MHRS most commonly occurs in the 4th been shown to play any significant role through 6th decades, affecting men in the hemolysis. The Coombs' test has more than women in a ratio of 3:1. been positive in only three of the pre­ Generally, it is rapidly fatal. However, viously reported cases. In two of these two cases of survival greater than three it became positive only after multiple years following splenectomy have been transfusions."'" Thrombocytopenia and reported recently.^ Symptoms and signs leukopenia, when present, also appears almost universally present are to be due in part to abnormal phagocy­ weakness, malaise, weight loss, pyrexia, tic activity by histiocytes.^^ splenomegaly and anemia. Less fre­ quent findings are edema or serous There seems to be little doubt that effusions (82%), hepatomegaly (78%), MHRS is a distinct clinical entity, charac­ leukopenia (69%), purpura (61%), jaun­ terized histologically by a proliferation dice (53%), and lymphadenopathy of malignant histiocytes which demon­ (52%). Skin lesions have been de­ strate a marked degree of erythro­ scribed in several cases."'' These have phagocytosis. It should be noted, had varied appearances, including dif­ however, that the descriptions of the fuse maculopapular rashes, reddish- hystiocytes have varied in different purple plaques and diffuse petechiae, cases, from benign-appearing cells to but there is no skin lesion characteristic obviously malignant reticulum cells. of MHRS. Commenting on the benign appearance of the histiocytes in their case, Fried­ The anemia, universally manifest dur­ man and Steigbigel" likened the entity ing the course of MHRS, may be in part to Letterer-Siwe disease rather than a due to Impaired red cell production sec­ true malignancy. Our case is of interest ondary to marrow replacement by in that islands of histiocytes, with vari­ tumor cells." The predominant and able morphologic degrees of malig­ characteristic type of anemia, however, nancy, could be demonstrated in all is hemolytic, an observation which has bone marrow sections at autopsy. Macken, Van Slyck and Saeed

In keeping with the concept pro­ leukemia, Letterer-Siwe disease, and posed by Rappaport,it seems proper mycosis fungoides. Clinically and to us that this disease be included as a pathologically these conditions are member of the malignant histiocytosis separable and should be dignified by a group of diseases, (see Table 1). As proper designation. The old term "his­ such, it requires a more decisive and tiocytic medullary reticulosis" is confus­ descriptive name than "reticulosis". ing and inaccurate, while the purely Proliferation of reticulum cells (his­ eponymic "Robb-Smith disease" con­ tiocytes) is the underlying common fea­ veys no information about the nature of ture of such diverse conditions as this disease entity. We suggest, there­ Hodgkin's disease, malignant lympho­ fore, a more informative compromise ma of the histiocytic variety (reti­ term, namely, "malignant histiocytosis culum cell sarcoma), Burkitt's of Robb-Smith type". lymphoma, histiocytic (monocytic)

References

1. Scott RB and Robb-Smith AHT: Histiocy­ 7. Liao KT, Rosai J, Daneshbod K: Malignant tic medullary reticulosis. Lancet 2:194, histiocytosis with cutaneous involve­ 22 July 1939 ment and eosinophilia. Amer f Clin Path 57:438-48, April 1972 2. Creenberg E, Cohen DM, Bease GL and Kyle RA: Histiocytic medullary 8. Friedman RM and Steigbigel NH: His­ reticulosis. Proc Staff Meet Mayo Clinic tiocytic medullary reticulosis. Amer f 37:271-83, 1962 Med 38:130-3, Jan 1965 3. Scamps RA, O'Neill BJ and Purser BN: 9. Lynch EC and Alfrey CP Jr: Histiocytic Histiocytic medullary reticulosis. Med medullary reticulosis. Ann Intern Med f Aust 2:956-60, 6 Nov 1971 63:666-71, Oct 1965 4. Anderson RG: Histiocytic medullary 10. Rappaport H: Tumors of the reticulosis with transient skin lesions. Hematopoietic System. In Atlas of Brit Med f 1:220-1, 12 Feb 1944 Tumor Pathology. Washington, DC, Armed Forces Institute of Pathology, 5. Natelson EA, Lynch EC, Hettig RA and Sec 3 - Fascicle 8, 1966, pp 49-63 Alfrey CB: Histiocytic medullary reticulosis. Arch Intern Med 122:223-9, 11. Willcox DRC: Haemolytic anaemia and Sept 1963 reticuloses. BR Med f 1:1322-5, 21 June 1952 6. Kalderon AE: Histiocytic medullary reticulosis associated with inclusion 12. Selegram BR, Rosner F, Lee SL and Kagan cytomegalic disease. Cancer 27:659-66, MD: Histiocytic medullary reticulosis. March 1971 Arch Intern Med 129:109-113, Jan 1972

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