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FILE NAME: Talc (TALC) DATE: 0000 DOC#: TALC031 DOCUMENT DESCRIPTION: Medical Journal Article - Talcum Powder Granuloma TALCUM POWDER GRANULOMA ROBERT FIENBERG, M.D. boston O il, one article dealing with talcum powder granuloma could be found n This was an article by Antopol,' devoted mamly L W c^" nuloma. A short description of one in which a foreign body reaction was fonnd ` ,e Pr" TM ( tropic crystals which morphologically resembled talc crystals (.mag " T y S r r ^ r h ^ l . who entered the hospital with a diagnosis of tumor of the abdominal wall. report of cases ,, , A 44 year old woman had had. an appendectomy and a hemiot- U i A - r- H Six years late, she had a slightly tender mass T5XSS " " L ,, , J L ,howcd An exploratory laparotomy ^ s^ m a d e , observed that an unusual gray . filtration fascia. On a c e of * * ^^ the entire cecum were slightly raised g J omentum wme seveml small of thin translucent granular ,issu' ,, E" stomach in the preaornc region. On much of the the abdomen was opened. Over S 'S d a r planes. I the nd generaiized scattering lay above the WJ , ,he gallHadder were di absent. The scar r T h e ^ is ir ^ r ^ ^ - -- -- ,-- -- - - " th ultimate course is nttaown. The specimen consisted of a Piece by 6 by 3 cm. The skin measured 9.5 ^ The tissue between the m m de and the ,,beuuneous tat and muscle. U d contained a scar 7 cm. long, dense, gray and . ^ ^ tissue extended into translucent, with opaque grayi the subcutaneous fat and conum in irregularly radiating manner. Also, cgu The i r e was a piece of connective tissue was firm, translucent, ..gm., s ^ -* From the Laboratory of Pathology. New England Detwotwss Hospital. M. : Texas State J. Med. 8*s482, 1936). F IE N B E R G --T A L Microscopic Examination.--Sec stain. An extensive lesion was si sue in which numerous pseudotu Talcum powder granuloma i Pseudotubercles containing numt invade the subcutaneous fat of thi corium, subcutaneous fat and mi of rounded collections of fibrobl foreign body giant cells. In addii tubercles, as well as a few infre NULOMA M.D. .vder granuloma could be Antopol,1 devoted mainly m o f one case was given, in the presence of anisolbled talc crystals (m ag >entered the hospital with FIENBERG-TALCUM POWDER GRANULOMA ^ k Z C J Z 7 l mti0n'~'SeCtiOaS Were' with eosin-methylene blue stam. An extensive lesion was seen, consisting of dense hyaline connective tis- s m which numerous pseudotubercles were present. The lesion involved the appendectomy and a herniorlination in the present instance, region of th old appendectomy l weight. Examination showed ipparently in the subcutaneous excision of the scar. It was r tissue occupied much of the e abdomen was opened. Over ducent nodular plaques. In the , and a generalized scattering m lymph nodes lay above the wall of the gallbladder were jpendix was absent. The scar of the anterior fascia, rectus iis paper was written, so that ibcutaneous fat and muscle, 12 and contained a scar 7 cm. long, neons fat was dense, gray and lae. This tissue extended into ilarly radiating manner. Also, sue, 6.5 by 3 by 1.5 cm. The granular and pinkish gray. gland Deaconess Hospital, m u has been described (Owen, Talcum powder granuloma (case 1 ); eosin-methylene blue stain; x 48 i'seudotubercles containing numerous multinucleated foreign body giant cells invade the subcutaneous fat of the abdominal wall. corium, subcutaneous fat and muscle. The more well defined nodules consisted f i S C0.IeCt,0nf, 0f fibroMasts and endothelial cells with numerous large b dy Ce S` In addltion- lymphocytes were noted within the pseudo tubercles, as well as a few infrequent polymorphonuclear leukocytes. Flattened, 38 ARCHIVES OF PATHOLOGY elongated fibroblasts occurred at the periphery. Here and there one or two giant cells were present, surrounded in some instances by a few endothelial cells. The giant cells contained numerous oval nuclei with small chromatin masses. These nuclei were at times arranged in a semicircle at the periphery and at other times were scattered throughout the cell. The cytoplasm of the giant cells was abundant, and often small spaces were visible within it, apparently containing crystals. In some regions coalescence of the nodules had occurred. Under crossed Nicol prisms, numerous anisotropic crystals were visible within the giant cells. The diagnosis was a foreign body reaction. Case 2.--A 67 year old woman five years previously had been given a diagnosis of primary hyperthyroidism, and had a subtotal thyroidectomy in two stages. The pathologic diagnosis was primary hyperplasia of the thyroid g an with moderate involution. In the present instance she was admitted for a swelling which had been present in the region of the thyroid gland during the past three years. The left lobe of the gland was easily felt; the isthmus was partly sub sternal. There was no evidence of hyperthyroidism. The basal metabolic rate was + 4 . It was felt that the remnants of the thyroid gland were a potential source of trouble and should be removed. . . An excision of the thyroid remnants was made. Following the operation, the basal metabolic rate was + 1 1 . , ,, . .. .. .. The specimen consisted of four irregular firm scraps of thyroid tissue, the total weight of which was 20 Gm. A small A o u n t of muscle was attached th e re was much increase in fibrous tissue. The thyroid tissue was translucent and pink. Microscopic Examination.--The sections were prepared with^the hematoxylin and eosin stain. An extensive lesion was seen, consisting of fibrosis an w developed pseudotubercles. Material staining with hematoxylin was present about some collections of crystals within giant cells. Under crossed Nicol prisms, numerous anisotropic crystals were found within The diagnosis was primary hyperplasia with late involution and hypermvolution, recurrent, and a foreign body reaction. A mineralogical analysis revealed that the crystals in the- giant cells in both the foregoing cases possessed the follow ing physical characteristics: ' 1. The extinction angle varied from 10 to 15 degrees. 2. Some crystals were in the orthorhombic and some in the mono clinic system. 3. The crystals had a. higher refractive index than Canada balsam (1 .5 4 ). Talc crystals possess an index of refraction of 1.589 along two axes. - 4. The crystals were anisotropic, 5. The crystals were roughly o f the same magnitude and morpho logic appearance as those iri talcum powder. Further evidence of a mineralogical nature was obtained by incin eration. Paraffin sections, unstained, were incinerated at about 400 C. for fiv tion in Th to an files o; cases 1 were ; other ( but it C as border in the lip at ; The pa Exa surgica was fir. enlarge slightly carcino A ' submax Mic area of eosin s fairly t ments < formati by and The obtaine slight i occurre Cas on the years \ formed at that was m An men cc membr indurat Mic stain, scar ti: taining In tissue 0OGY a and there one or two giant by a few endothelial cells, ith small chromatin masses, cle at the periphery and at cytoplasm of the giant cells ithin it, apparently containing les had occurred, c crystals were visible within >reviously had been given a subtotal thyroidectomy in two erplasia of the thyroid gland e was admitted for a swelling d gland during the past three . the isthmus was partly sub m. The basal metabolic rate lyroid gland were a potential de. Following the operation, scraps of thyroid tissue, the ount of muscle was attached, thyroid tissue w as'translucent irepared with the hematoxylin nmafititig of fibrosis and well hematoxylin was present about pic crystals were found within .te involution and hyperinvolu- the crystals in the giant ed the follow ing physical to IS degrees, bic and some in the mono index than Canada balsam refraction of 1.589 along ne magnitude and morpho- ure was obtained by incinindnerated at about 400 C. FIENBERG--TALCUM POWDER GRANULOMA for five hours on two successive days. Examination revealed no altera tion in the crystals. The significant results obtained in the study o f these two cases led to an investigation o f all the records o f foreign body reactions in the files of this laboratory. During a period of nine years only three other cases had occurred in which crystals resembling those in talcum powder were apparently responsible for clinically important lesions.. Several other cases were discovered in which a reaction to crystals was present, but it was overshadowed by that due to suture material. Case 3.--A SO year old woman had had a blue spot on the mucocutaneous border of the lower lip for a number of years. There had been a slight increase m the size of the lesion during a few months previous to an operation on the up at another hospital four weeks prior to examination in the present instance. The pathologic diagnosis was basal cell carcinoma. Examination showed on the left of the median line of the lower lip, a healed surgical scar 1 cm. in length. One portion of the scar, 0.4 cm. in diameter, was firm and nodular. In the left side of the neck there were from two to five enlarged palpable lymph nodes. The submaxillary gland on the left side was slightly larger than that on the right The clinical diagnosis was recurrent carcinoma. ' ^ V-shaped excision of the lesion was made, with later dissection of the submaxillary triangle. . . Microscopic Examination.--A segment of the lip containing a small indurated area of mucosa was sectioned, and the sections were treated with the hematoxylineosin stain. Dense scar tissue extended into the muscle from the corium, with fairly numerous foreign body giant cells present. Laterally, whorl-like arrange ments of fibroblasts surrounded the foreign body giant cells. The pseudotubercle formation was not well advanced. Numerous anisotropic crystals were surrounded by and contained within the foreign body giant cells. The diagnosis was a foreign body reaction. The diagnosis of the lesion in tissue obtained in the submaxillary dissection was hyperplasia of the lymph nodes and slight chronic inflammation of the submaxillary gland. (No anisotropic crystals occurred within the lymph nodes.) Case 4.--A 54 year old man had had, fifteen years previously, a furuncle on the left side of the lower lip about 2 cm. from the mucocutaneous line. Two years prior to examination in the present instance, a small nonulcerated Crater formed in the center of the old cicatricial tissue. This was treated with radium at that time. About one month, before examination, an excision of scar tissue was made at another hospital. The pathologic diagnosis was carcinoma. An excision of recurrent carcinoma and plastic repair were made. The speci men consisted of a small triangular piece of lip covered by skin and mucous membrane. The skin showed a small depressed area with some thickening and induration beneath it. . Microscopic Examination.-- Sections were prepared with the heraatoxylin-eosin stain. Dense scar tissue extended from the corium to the muscle. Withiji the scar tissue were small groups of foreign body giant cells surrounding and con taining anisotropic crystals. Scattered lymphocytes were present. In one section a small focus of tumor was surrounded by dense fibrous tissue in which numerous anisotropic crystals were present within foreign body 40 ARCHIVES OF PATHOLOGY giant cells. The tumor tissue was arranged in the form of hair follicles, occupying about three quarters of a low power field. Invasion was fairly active. The cells were small, with oval nuclei containing fine chromatin granules. The cyto plasm was scanty; the cell outlines, indistinct. Mitotic figures were not numerous. There was palisading of cells at the edges. . The diagnosis was chronic inflammation, scar tissue, a foreign body reaction and a small focus of basal cell carcinoma, apparently of the hair matrix type. (This focus was found only after many sections had been examined.) Case 5.--A 23 year old man had a swelling on the right side of the perineum, which appeared three weeks prior to his first admission to the hospital. This steadily increased in size and became tender. Examination disclosed that in the right anterior perineal region there was an egg-sized indurated tender swelling with fluctuation at the center. There was no induration along the wall of the rectum. Incision and drainage were carried out. The patient was again admitted two weeks later. An opening was made m the fistula seen at the site of the previous incision for drainage in the right anterior perineal region. A probe was passed along the left wall of the rectum, b u t n o internal opening could be demonstrated. The condition was diagnosed as blind external fistula in ano. Radical excision was performed. The specimen consisted of a piece of skin and subcutaneous fat, 4 by. 2.5 by 1.5 cm. The skin, 2.5 by 1 cm.; was traversed by an incision which ted into a sinus 12 by 02 cm. in diameter, running the lengthp i the specimen. There was blue discoloration about the incision. The surrounding tissue was fibrotic. Microscopic Examination.--Sections were prepared with the hematoxylin-eosin stain. The sinus tract was lined by granulation tissue, which was infiltrated with numerous lymphocytes. About the sinus tract was dense scar tissue, also heavily infiltrated with lymphocytes. This fibrosis extended into the fat. Within . the fibrous tissue were numerous anisotropic crystals, many of which were within numerous foreign body giant cells. Crystals and giant cells were close to the sinus. . ,, The diagnosis was a fistula with chronic. inflammation and a foreign body giant cell reaction. AH of the crystals in the last three cases resembled those found in the first two. Furthermore, in morphologic character they were strik ingly similar to talc crystals which were mounted in glycerin and examined under the microscope. y 1. EXPERIMENTAL STUDY Three adult mice were used. In each mouse 1 cc. of a sterilized 10 per cent sus pension of talcum powder in distilled water was injected subcutaneously mto the {.Morninal wall, as well as intraperitonealiy. At the end of seven weeks the mice were chloroformed and examined. The findings were more or less similar in all. Firm opaque white nodules about 0.3 cm. in diameter were found in the subcutaneous tissues of the anterior abdominal wall at the point of injection. WitBin the peritoneal cavity, similar nodules, covered by smooth serosa, were found on the serosal surfaces of the spleen, liver and small and large intestines, as well as within the mesentery of the small intestine and omentum. These nodules measured from 0.1 to 0.3 cm. in diameter. Some of the larger nodules, both in the anter of unalterec Microsco stain. The granulomatc containing : described. 1 a rather th endothelial visible. Thi and of the There w; invasion of centrally, w body giant but this wa remained in . In the showed th physical cl were prese morpholog: talc crysta |f^,jproduee le; I'lP y b u t by the It is of necessary 1 seven year error in th talc during ^ An ana ||M.by the van i \'cause of d: was done | | f during the 0 * by the diag only after the true na In the . and it was to be dan present. E In the i the lip. In )GY of hair follicles, occupying >ri was fairly active. The matin granules. The cytofigures were not numerous. ue, a foreign body reaction y of the hair matrix type, d been examined.) right side of the perineum, ssion to the hospital. This nation disclosed that in the d indurated tender swelling ition along the wall of the \ n opening was made in the 'ainage in the right anterior wall of the rectum, but no ion was diagnosed as blind ibcutaneous fat, 4 by. 2.5 by m incision which led into a of die specimen. There was og tissue was fibrotic. 1 with the hematoxylin-eosin issue, which was infiltrated was dense scar tissue, also ^tended into the fa t Within . . many of which were within pant cells were close to the nmation and a foreign body resembled those found in :haracter they were striknounted in glycerin and of a sterilized 10 per cent susected subcutaneously into the the end of seven weeks the gs were more or less similar i diameter were found in the all a t the point of injection, by smooth serosa, were found mall and large intestines, as and omentum. These nodules of the larger nodules, both FIENBERG--TALCUM POWDER GRANULOMA 41 1" " " * n i wit" n a e . S r5 rjsrtis: , * few polymorphonuclear Zana oSi tmne omenturm b?y the gran"u"lom<*a>tou1s <tiHsseue. * * of A , There was localized compression of the spleen and liver bv large nodules but no S r X l i S T t ^ 8' f thC ^ nodules>'crystals were present todv a L t rS k f " C Phag0Cytic cdls visibIe- Fibroblasts and foreign to T v? P? StBt 3t thc periphery- No tubercle formation was seen ^remramteha mr t^ne manimaalsl shatddbe^en cofamCpta^rative*ly shtimorCt. ^ Which * S y S 1 * * * ? ' **" resuIts t>iained following incineration showed that the crystals were mineral. This, together with their physical characteristics, makes it practically certain that talc crystals were present In the last three cases, the crystals were found to be morphologically identical w ith those in the first two cases and with talc crystals examined under the microscope. That talc crystals .may 1Iesions SHnilar to those found in the cases studied is brought out by the results obtained in animal experimentation. It is of great interest that in the first two cases the length of time necessary to produce clinically perceptible masses ranged from five to seven years. This t a g period-of time might be the cause of clinical error m that the possibility o f the introduction of a foreign body like talc during the previous operation might be forgotten. An analysis of the cases affords much instruction. One is struck . y the varied character o f the cases in which talc crystals introduced a cause o f diagnostic eiror. In the first case, an exploratory laparotomy was done for a suspected tumor o f the abdomen. Even examination unng J e operation did not reveal the error, which was further masked by the diagnosis of tuberculosis suggested.by the frozen section. It was only after the section was examined under crossed Nicol prisms that the true nature o f the lesion was suspected. In the second case, the patient had suffered from hyperthyroidism and it was natural that the nodules palpable in the neck were thought to be dangerous, although no symptoms of hyperthyroidism were present. Here, too, the presence o f a foreign body was unsuspected. thf nx t ,esions were presented in still another region, me Up. In the first o f these, recurrent carcinoma was suspected, but the 42 ARC H IVES OF PATHOLOGY nodule was found to be caused by a foreign body reaction to crystals. On the other hand, the presence o f crystals in the second case caused a lesion to be suspected which alone would probably have been missed for some time and in this way proved to be a boon to the patient. W hile the last case, one of a fistula in ano, presented no difficulty in diagnosis, it offered evidence that talc crystals in some instances may ,be responsible for keeping sinuses open. Although cases o f the type described are admittedly rare (5 in 30,000) the surgical lesions suggest that the indiscriminate use of talcum powder on gloves is to be avoided. W ashing the gloves before entering the operative field tends to prevent such granulomas. In view of the extensive use of the d iy teschnic, the rarity of such a complication sug gests the possibility o f individual variation in the reactions o f patients. The cases offer another example o f the harm fulness o f silicates in the human body. W hile rare, the lesions may be a cause o f diagnostic error. - ' . ... . ' SUMMARY ' , ' ' . " ' talfc'crystal .V < ... . The value of examination of suspicious sections Under crossed Nicol prisms is' stressed: A- : . ' V; . T he indiscriminate use of talcum powder ln th e operating room may produce granulomatous lesions. . . / T , PATH The pat have not 1 Flexner an snake veno .j'phemical pi Igw except Sstologic si j fe T M s pa] f f i |' ,ltiie 'tissu. The purpos he types c ' veen the atins seei P h isa lix ^ iO f this kinc 5 number of such a met than the sj - r edu jp ip ^ h i.8 - "" ms ef'^ F w m the ,1. Mitche ^Poisonous Se ^ & ^ v o L 26, 2. Flexne . i t - 1?03. ,1 1 3' Essex> | 70S, 1930. J t F 4. Phisali flf'1 9 2 2 , vol. 2, ; 5. Nowak 6. Flexne 7. Pearce