Adv Ther

https://doi.org/10.1007/s12325-019-01160-9

REVIEW

Paraneoplastic Syndromes Associated with Laryngeal

Cancer
Alessandra Rinaldo . Andrés Coca-Pelaz . Carl E. Silver .
Alfio Ferlito

Received: September 27, 2019

Ó The Author(s) 2019

ABSTRACT cancer’’ without any restrictions on language or

publication year. The full texts of all relevant
Objectives: Paraneoplastic syndromes occur articles were reviewed and all cases of paraneo-
rarely in association with laryngeal cancer. plastic syndromes associated with any type of
When present, the syndrome may be the first laryngeal cancer were extracted and analyzed.
sign of the malignancy. The aim of the present Results: We identified 59 cases of paraneoplas-
study was to review and report on all published tic syndromes related to laryngeal cancer in the
cases in the international literature. literature published from 1963 until recently.
Methods: A search of PubMed was conducted There were 46 squamous cell carcinomas and 10
for ‘‘paraneoplastic syndromes in laryngeal neuroendocrine carcinomas. Twenty-two of the
paraneoplastic syndromes involved the endo-
crine system, 21 were dermatologic or cuta-
This article was written by members of the International
neous, 8 neurologic, 5 osteoarticular or
Head and Neck Scientific Group (http://www.IHNSG.
com). rheumatologic, 1 ocular, 1 muscular, and 1
hematologic. Treatment strategies included
Enhanced Digital Features To view enhanced digital surgery, radiotherapy, chemotherapy, and often
features for this article go to https://doi.org/10.6084/
m9.figshare.10303700.
multimodal therapy, depending on the histol-
ogy and stage of the laryngeal cancer.
Conclusions: Because of their rarity, paraneo-
A. Rinaldo
University of Udine School of Medicine, Udine, Italy plastic syndromes associated with laryngeal
cancer are difficult to diagnose. By presenting
A. Coca-Pelaz and systematically reviewing all published cases
Department of Otolaryngology, Hospital
Universitario Central de Asturias, Oviedo, Spain in the international literature, the present
review may help clinicians to recognize them
A. Coca-Pelaz and to suspect the diagnosis of laryngeal cancer
Instituto de Investigación Sanitaria del Principado
de Asturias, IUOPA, CIBERONC, Oviedo, Spain
at an earlier stage than otherwise might be
possible.
C. E. Silver
Department of Surgery, University of Arizona
College of Medicine, Phoenix, AZ, USA Keywords: Cancer of the larynx; Diagnosis;
Larynx; Metastasis; Paraneoplastic syndromes;
A. Ferlito (&) Recurrence
International Head and Neck Scientific Group,
Padua, Italy
e-mail: [email protected]
 Adv Ther

phenomena, paraneoplastic disturbances, or

Key Summary Points remote effects. Paraneoplastic syndromes are
more often recognized at the present time than
Paraneoplastic syndromes occur rarely in previously, because of improving diagnostic
association with laryngeal cancer. methods and greater current knowledge about
them among clinicians [6–9].
When present, the syndrome may be the Small cell lung cancer is the tumor most
first sign of the malignancy. frequently associated with these syndromes,
A search of PubMed was conducted for although they can occur in almost any type of
‘‘paraneoplastic syndromes in laryngeal malignant tumor [10].
cancer’’. Laryngeal cancers, regardless of histology,
have rarely been associated with paraneoplastic
Paraneoplastic syndromes associated with syndromes [1, 2, 11–13]. In this manuscript we
laryngeal cancer are difficult to diagnose. will group these syndromes into seven head-
Recognizing a paraneoplastic syndrome ings: (1) dermatologic or cutaneous, (2) endo-
helps in suspecting a laryngeal cancer. crine, (3) hematologic, (4) neurologic, (5)
osteoarticular or rheumatologic, (6) ocular, and
(7) muscular.
This article is based on previously conducted
studies and does not contain any studies with
INTRODUCTION human participants or animals performed by
any of the authors.
The symptoms and signs of various cancers are
caused by the effects of the neoplasm locally,
regionally, or distantly. In a few patients, these METHODS
signs and symptoms are not directly produced
by the primary tumor or its metastases, In order to identify all published cases of parane-
appearing rather to be produced by other, per- oplastic syndromes associated with laryngeal
haps humoral, but often not fully understood cancer, we performed a review of the more rele-
mechanisms. These conditions are called vant articles that cover this issue. For this purpose,
‘‘paraneoplastic syndromes’’ and their location the Preferred Reporting Items for Systematic
does not coincide with the site of tumor [1–3]. Review and Meta-Analyses (PRISMA) method was
Paraneoplastic syndromes are rare clinical syn- used to conduct a systematic review of the current
dromes due to the systemic effects of tumors; literature [14]. A PubMed internet search updated
they are unrelated to tumor size, invasiveness, to March 3, 2019 was performed for publications
or metastases [4]. A paraneoplastic syndrome using the following search terms in the title or
may be the first indication of an underlying abstract: ‘‘paraneoplastic syndrome’’ coupled with
cancer (initial, persistent or recurrent tumor, or ‘‘head and neck cancer’’ or ‘‘larynx cancer’’. The
asymptomatic metastasis). It is not due to direct search results were reviewed for potentially eligi-
organ invasion but is caused by substances ble studies. When the abstract indicated that the
elaborated by the distant neoplasm. These syn- article included a report of a paraneoplastic syn-
dromes may precede the presentation of a can- drome, the full-text article was searched and
cer by many months, occasionally by several reviewed in order to know if the tumor was loca-
years. Whatever hormones and/or antibodies ted in the larynx, excluding primary tumors at any
produce these syndromes, they share the prop- other sites (e.g., hypopharynx). All articles were
erty of acting far from their site of synthesis [5]. checked in full text for cross-references. Refer-
Other terminology for paraneoplastic syn- ences from full-text articles were cross-checked to
dromes includes paraneoplastic conditions, ensure inclusion of all relevant publications in
paraneoplastic effects, paraneoplastic events, this review. Selected studies met the following
non-metastatic syndromes, paraneoplastic inclusion criteria: (1) patients diagnosed with a
Adv Ther

paraneoplastic syndrome, (2) location of the subglottic (28 not stated). Histology was not
tumor specified in the text within the larynx. mentioned in 3 cases. Most of the identified
Studies in which the location of the primary laryngeal cancers were squamous cell carcinoma
tumor was not specified clearly, or which were (n = 46) (46/56: 82.1%) followed by neuroen-
referred to as located in the larynx but were loca- docrine carcinoma (n = 10) (10/56: 17.9%).
ted in the pyriform sinus were excluded. Endocrine (n = 22) and dermatologic or cuta-
neous (n = 21) paraneoplastic syndromes were
the most prevalent, followed by neurologic
RESULTS (n = 8), osteoarticular or rheumatologic (n = 5),
ocular (n = 1), muscular (n = 1), and hemato-
Selection of Included Studies logic (n = 1) syndromes. Applied treatment
strategies included surgery, radiotherapy,
The initial search identified 174 original articles, chemotherapy, and often multimodal therapy,
42 of which were excluded on the basis of the according to the site and stage of the tumors.
aforementioned search criteria. Full texts of the Twenty-eight patients underwent surgery for
remaining 132 studies were assessed. Of these, the treatment of the primary tumor that caused
85 articles were excluded as they did not include the paraneoplastic syndrome, 23 received
cases of laryngeal cancer with paraneoplastic radiotherapy, 11 patients were treated with
syndromes, or the primary site was not specifi- chemotherapy, and 20 patients underwent dif-
cally defined. This selection process resulted in ferent multimodal treatment for their condi-
the final inclusion of 47 articles (Fig. 1). tion. Survival outcome differed highly among
the published cases; 19 patients were alive, and
Description of Included Cases 23 patients had died of disease at the times of
publication. However, the value of these sur-
In the selected articles, we identified in total 59 vival data is questionable as follow-up data are
cases of paraneoplastic syndromes related to very often not included in the original articles
laryngeal cancer in the published literature or the follow-up time is very short.
from 1963 until recently. The average age of the
patients was 61.55 years (median 61.5 years,
LITERATURE REVIEW
range 45–78 years); age was unknown in 19
cases. There were 36 men and 7 women (16 WITH DISCUSSION
gender not stated). In 18 cases the primary
tumor was supraglottic, 12 cases glottis, and 1 Paraneoplastic Dermatologic
or Cutaneous Syndromes

Several paraneoplastic dermatologic or cuta-

neous syndromes have been reported [15].
Acanthosis nigricans, Bazex syndrome, bullous
pemphigoid, dermatomyositis, yellow nail syn-
drome, tylosis, pityriasis rubra pilaris, and
Leser–Trélat sign were observed in various
patients with laryngeal cancer.

Acanthosis Nigricans
Acanthosis nigricans is a cutaneous condition
characterized by hyperpigmented papilloma-
tous plaques that usually affects flexor areas
symmetrically, but it can be seen in any part of
Fig. 1 Flow chart showing the process of the study the body. When related to a malignant tumor,
selection for the systematic review
 Adv Ther

the condition appears abruptly, with rapid and coincidental association. Currently, it is sug-
extensive progression. The most frequently gested that the term ‘‘paraneoplastic pem-
experienced association is with abdominal ade- phigoid’’ be avoided. ‘‘Pemphigoid associated
nocarcinoma (60% are stomach cancer), but with malignancies’’ is preferred [34].
there have been cases associated with laryngeal
tumors [16]. Dermatomyositis
Dermatomyositis is an idiopathic inflammatory
Bazex Syndrome disease that can produce degenerative and
Bazex syndrome (also named Bazex’s acroker- inflammatory damage to muscle and skin in a
atosis paraneoplastica, acrokeratosis paraneo- symmetrical and progressive way. Despite its
plastica, acrokeratosis Bazex) is clinically unknown cause, it has been associated with
characterized by erythematous squamous erup- different tumors (lung, larynx, breast, and oth-
tions that spread centripetally from the finger- ers) [35, 36].
tips and toes, ears, nose, and other sites.
Occasionally, vesicles, bullae, and crusts Yellow Nail Syndrome
have been described. Symmetrical distribution Yellow nail syndrome has been reported in
is the norm. This syndrome has most often been patients affected by larynx cancer. The syn-
associated with malignant tumors located above drome always regressed after treatment of the
the diaphragm, and is most commonly associ- tumor [37]. The syndrome is characterized by
ated with head and neck cancers (oral cavity, nail discoloration and is associated with lym-
pharynx, larynx, and others) with nodal phedema (considered secondary to anomalies of
involvement [17, 18]. It has also been associated lymphatic drainage), and also with bronchiec-
with cancers from other locations (including tasis and sinusitis.
bronchus, thymus, prostate, uterus) and with
different histologic types (myeloma, adenocar- Tylosis
cinoma, anaplastic carcinoma, and others) [19]. Tylosis, or hyperkeratosis, occurs on the palms
Bazex’s acrokeratosis is the most frequent of the hands (palmarum) or the plantar region
paraneoplastic syndrome associated with of the foot (plantarum). Esophageal and, less
tumors located in the larynx [17, 19–30]. commonly, laryngeal cancer may occur in
Occasionally, other cutaneous paraneoplastic association [38]. This disorder is considered
syndromes (Bazex syndrome, hyperpigmenta- paraneoplastic.
tion, and acquired ichthyosis) have been
reported in patients with larynx cancer [21].
Pityriasis Rubra Pilaris
In some cases, laryngeal cancer had been
Pityriasis rubra pilaris constitutes a cluster of
diagnosed because of the appearance of a cuta-
papulosquamous dermatoses often confused
neous paraneoplastic syndrome [31, 32].
with various skin disorders (psoriasis in partic-
ular). This disease possibly results from dysreg-
Bullous Pemphigoid ulation of the immune system as well as
Bullous pemphigoid is a common autoimmune unusual response to certain antigens associated
blistering disorder of the skin and has been with rheumatological diseases, trauma and
observed in patients with various malignant infections (human immunodeficiency virus),
tumors, although the significance of this asso- hypothyroidism, and solid and hematological
ciation is controversial [33]. Some studies show malignancies. The syndrome has occurred in
an obvious association between malignancies cases of laryngeal cancer [39].
and bullous pemphigoid, but other studies have
failed to demonstrate a higher risk of malig-
Leser–Trélat
nancies among patients with bullous pem-
The Leser–Trélat sign, characterized by the
phigoid. The question remains whether in these
sudden occurrence of multiple seborrheic ker-
cases bullous pemphigoid is a paraneoplasia or a
atoses, often with associated pruritus, is
Adv Ther

considered a marker of internal malignancy. Bishop et al. [52] reported on the first case of small
Acanthosis nigricans can occur in 20% of such cell neuroendocrine carcinoma of the larynx
cases. The most frequently reported malignan- associated with ectopic ACTH syndrome. The cell
cies associated with the Leser–Trélat sign are cytoplasm was immunoreactive for ACTH, gas-
stomach cancer, lymphoma, and gastrointesti- trin-releasing polypeptide, neuron-specific eno-
nal adenocarcinoma. There are also reports of lase, b-endorphin, calcitonin, and keratin, by
occurrence in cases of laryngeal cancer [40]. indirect immunoperoxidase techniques.

Paraneoplastic Endocrine Syndromes Schwartz–Bartter Syndrome

Schwartz–Bartter syndrome (syndrome of inap-
Production of polypeptide hormones is the propriate secretion of antidiuretic hormone,
causative factor in paraneoplastic endocrine SIADH) was first described by Schwartz et al.
syndromes related to lung, breast, carcinoids, [53] in two patients with bronchogenic carci-
and thyroid medullary cancer. noma. The syndrome is characterized by ectopic
synthesis and excretion of vasopressin by cancer
Carcinoid Syndrome cells that leads to impaired excretion of free
Carcinoid syndrome (carcinoidosis or water, water intoxication, and hyponatremia.
argentaffinosis) most often is associated with The reduced sodium level is due both to an
metastatic neuroendocrine neoplasms (lung, enlarged amount of extracellular fluid and to its
gastrointestinal tract, ovary, etc.) [41–43]. The higher urinary excretion.
four major components of this syndrome are In the head and neck, SIADH is a well-known
episodic diarrhea, skin flushing, affecting the form of paraneoplastic syndrome. In a review by
face and the upper trunk, carcinoid heart dis- Ferlito et al. [11], 70 cases of this syndrome were
ease, and bronchospasm. Dermatitis and found to be associated with head and neck
depression occur less commonly. Some patients cancers. Oral cavity was the commonest loca-
can manifest all of the above symptoms. tion of the primary tumor (29 cases). Thirteen
Most neuroendocrine malignancies of the cases involved the larynx. Squamous cell carci-
larynx reported in the literature were nonfunc- noma was the predominant histology [54–58].
tional and, therefore, without clinical syn- Three cases were small cell neuroendocrine
dromes [1, 12, 44, 45]. Five cases of laryngeal carcinoma [59–61]. SIADH may precede the
neuroendocrine carcinomas (one well differen- diagnosis of the cancer by several months.
tiated, one large cell, and three moderately dif- Patients may present with initial headache,
ferentiated) with a carcinoid syndrome were confusion and temporo-spatial disorientation,
reported [46–50]. The case described by Over- hyperreflexia, reduced levels of sodium, chlo-
holt et al. [48] as moderately differentiated rine and osmolarity, decreased hematocrit,
neuroendocrine carcinoma has recently been negative free-water clearance, and elevation of
considered to have been a large cell neuroen- antidiuretic hormone. These tumors appear to
docrine carcinoma (Leon Barnes and James S. have a very poor prognosis, as all these patients
Lewis Jr., personal communication, 2019). died despite adequate therapy.
Nine of the ten patients affected by a parane-
oplastic syndrome [carcinoid syndrome, Hypercalcemia
Schwartz–Bartter syndrome, Eaton–Lambert syn- Hypercalcemia, which is the most frequently
drome, adrenocorticotropic hormone (ACTH) occurring metabolic complication of malignancy
syndrome] died. Only one patient was alive with [62], often occurs during the late stages of malig-
disease after 42 months of follow-up [13]. nancy. Hypercalcemia is a complication of many
advanced tumors including carcinomas of the
Ectopic ACTH Syndrome ovary, kidney, esophagus, and the head and neck,
Ectopic ACTH syndrome was reported in associ- hematopoietic malignancies, and solid sarcomas
ation with a larynx cancer by Imura et al. [51]. [63, 64]. An uncommon cause is bone metastasis
 Adv Ther

[65]. Many tumors cause hypercalcemia due to ovary, and breast cancer [2], and occasionally
inappropriate hormonal regulation. Patients with with larynx cancer [74, 75]. It is primarily
laryngeal cancer often have hypercalcemia in the characterized by a wide-legged, unsteady,
absence of metastasis [65]. Parathyroid hormone- lurching walk accompanied by a back and forth
related protein (PTHrP) is not confined to malig- tremor in the trunk and the body. Slow,
nancy-associated hypercalcemia, and sufficient unsteady, and jerky movement of the arms or
evidence now also supports its role in skeletal legs, slowed and allured speech, and nystagmus
metastasis (through its modulation of bone may also be observed. The cause may be
turnover), as well as in tumor progression and immunologic cross-reactions, and antineural
metastasis [66]. Clinical signs of mild hypercal- antibodies, that are found in about 50% of the
cemia include anorexia, constipation, abdominal patients [6, 76]. The better known paraneo-
pain, nausea and vomiting, thirst with polyuria, plastic neurologic syndromes are those with
myalgias, weakness, fatigue, headaches, depres- specific antibodies associated, and the clinical
sion, and confusion. Hypercalcemia is a medical signs of these syndromes can precede clinical
emergency [67]. Hypercalcemia associated with signs of the cancer [77].
advanced malignancy portends a dismal prog-
nosis. Hypercalcemia is managed by treatment of Ataxia
the cancer responsible for it [67]. Ataxia as a manifestation of cerebellar involve-
ment is infrequent among the neurological
Paraneoplastic Hematologic Syndromes manifestations of paraneoplastic syndromes
and histologically usually corresponds to a dif-
Paraneoplastic hematologic syndromes are fuse massive loss of Purkinje cells, with little
more commonly associated with other malig- alteration of the white substance and frequent
nancies than cancer of the larynx. inflammatory signs. Clinically, it is manifested
by a nonspecific cerebellar pattern with insta-
Trousseau Syndrome bility and dissymmetry that sometimes incor-
Trousseau syndrome (disseminated intravascular porates vestibular signs (spontaneous
coagulation or thromboembolism) was first nystagmus). Garcia et al. [78] published a case of
reported by Armand Trousseau [68]. Trousseau paraneoplastic ataxia due to a supraglottic lar-
described thrombotic events related to gastric ynx cancer. After surgery, ataxia was resolved
cancer. Trousseau syndrome has been related to within 3 weeks.
cancer of the pancreas, and occurred with ovar-
ian, lung, colon, and breast cancer [69]. This Eaton–Lambert Myasthenic Syndrome
syndrome is rare (less than 1% [70]) in head and Eaton–Lambert myasthenic syndrome was
neck cancers, although it has occurred in patients reported by Lambert et al. [79]. The complete
with laryngeal cancer [71]. It is diagnosed by the syndrome was further delineated by Eaton and
findings of thrombocytosis and elevated fibrin Lambert [57, 80]. The same disease had previ-
levels. Thrombosis of unknown cause may be the ously been described by Gray and Halton [81]. It
first manifestation of cancer [72, 73]. is usually associated with small cell lung cancer
[82], but also with larynx cancer [83–86]. As
Paraneoplastic Neurologic Syndromes with cerebellar degeneration, the detection of
serum and cerebrospinal fluid autoantibodies
can be helpful for diagnosis.
Paraneoplastic neurologic syndromes fre-
quently occur in cancer patients, but they are
uncommon when the primary site is the larynx. Encephalomyelitis
Encephalomyelitis has been considered as a
paraneoplastic syndrome associated with small
Cerebellar Degeneration
cell lung cancer [7, 87]. There is abundant evi-
Cerebellar degeneration, or cerebellar cortex
dence in the literature that the anti-Hu
degeneration, may be associated with lung,
Adv Ther

antibody is a marker of encephalomyelitis [7]. normal or might reveal arteriolar narrowing.

Two cases of laryngeal cancer have been asso- The electroretinogram reveals abnormal cone
ciated with this syndrome [88, 89]. and rod-mediated signals [94].

Paraneoplastic Osteoarticular Cancer-Associated Retinopathy (CAR)

or Rheumatologic Syndromes and Melanoma-Associated Retinopathy (MAR)
The most frequently occurring paraneoplastic
Paraneoplastic osteoarticular or rheumatologic ocular syndromes are cancer-associated
syndromes occur rarely in laryngeal cancer and retinopathy (CAR) and melanoma-associated
small cell lung carcinomas. retinopathy (MAR). Parc et al. [95] reported on
CAR syndrome in a patient who complained of
Polyarthritis photophobia and bilateral visual loss who had a
Polyarthritis has been associated with different laryngeal cancer extirpated 18 months
cancers, both solid and hematological, and may previously.
be the earliest presentation of the malignancy.
A neoplastic cause must be ruled out in any case Paraneoplastic Muscular Syndromes
of recently appearing polyarthritis [90].
Eggelmeijer and Macfarlane [91] reported an Paraneoplastic muscular syndromes like
instance of larynx cancer associated with polymyositis are idiopathic inflammatory
polyarthritis. myopathies linked with cancer, but less fre-
quent than dermatomyositis. Both conditions,
Pseudo-Still Disease polymyositis and dermatomyositis, present
Cabane et al. [92] reported on an instance of with proximal, symmetric muscle weakness.
aryepiglottic fold carcinoma in association with Clinical features along with raised creatine
pseudo-Still disease, which is an inflammatory phosphokinase (CPK) and positive muscle
type of arthritis distinguished by pain, swelling, biopsy are required for diagnosis. According to
and tenderness in one or more joints along with Hill et al. [96] about 30% of dermatomyositis
splenic enlargement and lymphadenopathy. and 15% of polymyositis patients were found to
have associated cancer, with approximately
Hypertrophic Osteoarthropathy 60% of the malignancies diagnosed after the
The syndrome of hypertrophic osteoarthropa- onset of myopathy. Most were detected within
thy is distinguished by ‘‘clubbing’’ of the digits 1 year of presentation of myositis and the type
of the hand and/or foot, periosteal reaction, and of cancer most often associated was adenocar-
arthralgia or arthritis which is the same syn- cinoma. Associated carcinomas observed in
drome associated with cyanotic congenital previous studies were ovarian, lung, cervical,
heart disease and chronic pulmonary infec- pancreatic, stomach, colorectal, and non-
tions. It may also occur in patients with carci- Hodgkin’s lymphoma.
noma of the lung (particularly squamous cell Sahu et al. [97] reported a case of a laryngeal
carcinoma). Mackenzie and Scherbel [36] and cancer associated with polymyositis. With the
Cohen [93] described three instances of this treatment of the laryngeal cancer, the patient
syndrome in patients with cancer of the larynx. achieved almost normal muscle strength with
normalization of CPK level after 6 months.
Table 1 summarizes paraneoplastic syn-
Paraneoplastic Ocular Syndromes
dromes reported to have occurred in patients
Paraneoplastic ocular syndromes are distin-
with cancer of the larynx [16, 17, 23, 26, 27,
guished by progressive functional loss of pho-
30, 33, 35–40, 46–52, 55–61, 65, 71, 75, 78, 83–
toreceptors and subsequent painless loss of
86, 88, 89, 91–93, 95, 97–102].
vision, light-induced glare, night blindness,
photosensitivity, and peripheral ring-like sco-
tomas. Fundoscopic examination may be
Table 1 Paraneoplastic syndromes in patients with cancer of the larynx
Paraneoplastic Paraneoplastic syndrome Author (Refs.) Year Age Sex Site Type of Treatment Follow-
syndrome type name (years) tumor up
Dermatologic or Acanthosis nigricans Oppolzer et al. [16] 1986 76 M G SCC S ? RT Alive
cutaneous Bazex syndrome Colomb et al. [23] 1981 68 M SG SCC RT Alive
Rubisz-Brzezinska et al. 1983 78 M G SCC None DOD
[98]
Mounsey and Brown [27] 1992 66 M G SCC RT ? S DOD
Miquel et al. [26] 1997 64 M SG SCC S ? RT Alive
Khachemoune et al. [17] 2004 70 M NA SCC S?C NA
Aksu and Karadeniz [30] 2006 62 M G SCC RT Alive
Ehmann et al. [99] 2012 49 F NA SCC RT ? C ? S Alive
Bullous pemphigoid Hodge et al. [33] 1981 NA NA NA SCC NA NA
Dermatomyositis Mackenzie and Scherbel 1963 66 M G SCC S NA
[36]
Tsvetkov [100] 1977 61 M SG SCC RT Alive
Bonnetblanc et al. [35] 1990 NA NA NA SCC NA Alive
Zhang et al. [101] 2009 NA NA NA NA NA NA
NA NA NA NA NA NA
NA NA NA NA NA NA
Yellow nail syndrome Guin and Elleman [37] 1979 61 M NA SCC S Alive
Tylosis Haines [38] 1967 66 M G SCC RT DOD
Pityriasis rubra pilaris Batinac et al. [39] 2009 46 M G SCC in situ S Alive
Leser–Trélat sign Rubisz-Brzezinska et al. 1983 78 M G SCC None DOD
[98]
Nyati et al. [40] 2016 NA M SG SCC RT ? C ? RT Alive
NA F G SCC RT Alive
Adv Ther
Table 1 continued
Paraneoplastic Paraneoplastic syndrome Author (Refs.) Year Age Sex Site Type of Treatment Follow-
Adv Ther

syndrome type name (years) tumor up

Endocrine Carcinoid syndrome Baugh et al. [46] 1987 50 F SG MDNC S DOD

Wenig and Gnepp [49] 1989 NA M SG WDNC S?C Alive
a
Overholt et al. [48] 1995 57 M SG LCNC S ? RT ? S DOD
Kumai et al. [47] 1996 74 M SG MDNC S DOD
Yamanaka et al. [50] 1997 NA NA NA MDNC NA DOD
Ectopic ACTH syndrome Imura et al. [51] 1975 66 M NA SCC S DOD
Bishop et al. [52] 1985 60 F SG SCNC RT DOD
Schwartz–Bartter syndrome Moses et al. [55] 1976 NA NA NA SCC NA NA
(SIADH) NA NA NA SCC NA NA
Trotoux et al. [59] 1979 61 M SuG SCNC S ? RT DOD
Takeuchi et al. [60] 1989 53 M SG SCNC S DOD
Zohar et al. [58] 1991 62 M SG SCC S?C DOD
65 M NA SCC S ? RT ? C DOD
63 M NA SCC None DOD
Talmi et al. [57] 1992 NA NA NA SCC NA NA
NA NA NA SCC NA NA
NA NA NA SCC NA NA
NA NA NA SCC NA NA
Roth et al. [56] 1994 76 M NA SCC S ? RT DOD
Myers and Kessimian 1995 58 M SG SCNC C DOD
[61]
Maxwell and Witterick 2004 52 M SG SCC RT ? S ? C DOD
[102]
Hypercalcemia Angel et al. [65] 1982 52 F NA SCC S ? RT DOD
Table 1 continued
Paraneoplastic Paraneoplastic syndrome Author (Refs.) Year Age Sex Site Type of Treatment Follow-
syndrome type name (years) tumor up

Hematologic Trousseau syndrome Nikšic and Balogh [71] 1976 NA NA NA SCC NA NA

Neurologic Cerebellar degeneration Müller et al. [75] 1969 NA NA NA SCC NA NA
Ataxia Garcia et al. [78] 1998 66 M SG SCC S Alive
Eaton–Lambert myasthenic Fontanel et al. [83] 1973 58 M G SCC S Alive
syndrome Medina et al. [84] 1984 64 F SG SCNC C ? RT DOD
Ferroir et al. [85] 1989 58 M G SCC C ? RT DOD
Shipley et al. [86] 2008 64 M G SCC S NA
Encephalomyelitis Baijens and Manni [88] 2006 74 M SG SCC None DOD
Erro Aguirre et al. [89] 2016 53 M NA SCC S ? RT Alive
Osteoarticular or Polyarthritis Eggelmeijer and 1992 50 M SG SCC S ? RT Alive
rheumatologic Macfarlane [91]
Pseudo-Still disease Cabane et al. [92] 1988 45 M SG SCC C ? S ? RT Alive
Hypertrophic osteoarthropathy Mackenzie and Scherbel 1963 NA NA NA SCC NA NA
[36] NA NA NA SCC NA NA
Cohen [93] 1993 66 M NA SCC S DOD
Ocular Cone dysfunction Parc et al. [95] 2006 50 F NA SCC NA Alive
Muscular Polymyositis Sahu et al. [97] 2016 54 M NA SCC S ? RT Alive
SCC squamous cell carcinoma, WDNC well-differentiated neuroendocrine carcinoma, MDNC moderately differentiated neuroendocrine carcinoma, LCNC large
cell neuroendocrine carcinoma, SCNC small cell neuroendocrine carcinoma, M male, F female, G glottic, SG supraglottic, SuG subglottic, DOD dead of disease,
S surgery, C chemotherapy, RT radiotherapy, NA not available
a
Leon Barnes and James S. Lewis Jr., personal communication, 2019
Adv Ther
Adv Ther

CONCLUSIONS credit to the original author(s) and the source,

provide a link to the Creative Commons license,
Paraneoplastic syndromes in laryngeal cancer and indicate if changes were made.
occur infrequently and therefore are difficult to
diagnose. The histology most frequently asso-
ciated with paraneoplastic syndromes was
squamous cell carcinoma and the most frequent
REFERENCES
location was supraglottic. By presenting and
systematically reviewing all published cases in 1. Ferlito A, Rinaldo A. Paraneoplastic syndromes in
patients with laryngeal and hypopharyngeal can-
the international literature, the present review cers. Ann Otol Rhinol Laryngol. 2000;109:109–17.
may help clinicians to recognize them.
2. Ferlito A, Rinaldo A. Paraneoplastic syndromes in
patients with cancer of the larynx and hypophar-
ynx. Ann Otol Rhinol Laryngol. 2007;116:502–13.
ACKNOWLEDGEMENTS
3. Agaimy A. Paraneoplastic syndromes. Semin Diagn
Pathol. 2019;36:203–92.
Funding. No funding or sponsorship was 4. Henry K. Paraneoplastic syndromes: definitions,
received for this study or publication of this classification, pathophysiology and principles of
article. treatment. Semin Diagn Pathol. 2019;36:204–10.

Authorship. All named authors meet the 5. Ferlito A, Friedmann I. Neuroendocrine neoplasms.
In: Ferlito A, editor. Neoplasms of the larynx.
International Committee of Medical Journal Edinburgh: Churchill Livingstone; 1993. p.
Editors (ICMJE) criteria for authorship for this 169–205.
article, take responsibility for the integrity of
the work as a whole, and have given their 6. Mason WP, Graus F, Lang B, et al. Small-cell lung
cancer, paraneoplastic cerebellar degeneration and
approval for this version to be published. the Lambert–Eaton myasthenic syndrome. Brain.
1997;120:1279–300.
Disclosures. Andrés Coca-Pelaz and Carl E.
Silver have nothing to disclose. Alessandra 7. Dalmau JO, Posner JB. Paraneoplastic syndromes.
Arch Neurol. 1999;56:405–8.
Rinaldo and Alfio Ferlito are both members of
this journal’s Editorial Board but have no other 8. Sillevis Smitt P, Grefkens J, de Leeuw B, et al. Sur-
relevant conflicts of interest to disclose. vival and outcome in 73 anti-Hu positive patients
with paraneoplastic encephalomyelitis/sensory
Compliance with Ethics Guidelines. This neuronopathy. J Neurol. 2002;249:745–53.
article is based on previously conducted studies 9. Dropcho EJ. Update on paraneoplastic syndromes.
and does not contain any studies with human Curr Opin Neurol. 2005;18:331–6.
participants or animals performed by any of the
authors. 10. Gandhi L, Johnson BE. Paraneoplastic syndromes
associated with small cell lung cancer. J Natl Compr
Canc Netw. 2006;4:631–8.
Data Availability. All data generated or
analyzed during this study are included in this 11. Ferlito A, Rinaldo A, Devaney KO. Syndrome of
published article. inappropriate antidiuretic hormone secretion asso-
ciated with head and neck cancers: review of the
literature. Ann Otol Rhinol Laryngol. 1997;106:
Open Access. This article is distributed 878–83.
under the terms of the Creative Commons
Attribution-NonCommercial 4.0 International 12. Ferlito A, Shaha AR, Rinaldo A. Paraneoplastic syn-
License (http://creativecommons.org/licenses/ dromes in neuroendocrine neoplasms of the head
and neck: have they an impact on prognosis? (Edi-
by-nc/4.0/), which permits any non- torial). Acta Otolaryngol. 2001;121:756–8.
commercial use, distribution, and reproduction
in any medium, provided you give appropriate
 Adv Ther

13. Ferlito A, Rinaldo A, Bishop JA, et al. Paraneoplastic 26. Miquel FJ, Zapater E, Vilata JJ, Gil MP, Garin L.
syndromes in patients with laryngeal neuroen- Paraneoplastic acral hyperkeratosis: initial sign of
docrine carcinomas: clinical manifestations and laryngeal neoplasia. Otolaryngol Head Neck Surg.
prognostic significance. Eur Arch Otorhinolaryngol. 1997;117:S239–42.
2016;273:533–6.
27. Mounsey R, Brown DH. Bazex syndrome. Oto-
14. Shamseer L, Moher D, Clarke M, et al. Preferred laryngol Head Neck Surg. 1992;107:475–7.
reporting items for systematic review and meta-
analysis protocols (PRISMA-P) 2015: elaboration 28. Plasencia DP, Lazarich JMC, Macias AR. Acroker-
and explanation. BMJ. 2015;350:g7647. atosisparaneoplastica (Bazex syndrome) with ear
manifestation. Mediterranean J Otol. 2005;1:
15. Kurzrock R, Cohen PR. Cutaneous paraneoplastic 148–51.
syndromes in solid tumors. Am J Med. 1995;99:
662–71. 29. Sarkar B, Knecht R, Sarkar C, Weidauer H. Bazex
syndrome (acrokeratosisparaneoplastica). Eur Arch
16. Oppolzer G, Schwarz T, Zechner G, Gschnait F. Otorhinolaryngol. 1998;255:205–10.
[Acanthosis nigrigans in squamous cell carcinoma
of the larynx]. Z Hautkr. 1986;61:1229–37. (Article 30. Aksu G, Karadeniz A. Cutaneous paraneoplastic
in German). syndrome (acrokeratosisparaneoplastica) preceding
squamous cell carcinoma of the glottic larynx. N Z
17. Khachemoune A, Yalamanchili R, Rodriguez C. Med J. 2006;119:U2006.
Bazex syndrome (paraneoplastic acrokeratosis).
Cutis. 2004;74:289–92. 31. Milewski C, Wieland W. Paraneoplastische Akro-
keratose: M. Bazex Eine tumorspezifische Der-
18. Valdivielso M, Longo I, Suarez R, Huerta M, Lazaro matose bei Plattenepithelkarzinomen im Kopf-
P. Acrokeratosis paraneoplastica: Bazex syndrome. Halsbereich. HNO. 1988;36:158–60.
J Eur Acad Dermatol Venereol. 2005;19:340–4.
32. Wareing MJ, Vaughan-Jones SA, McGibbon DH.
19. Laccourreye O, Laccourreye L, Jouffre V, Brasnu D. Acrokeratosisparaneoplastica: Bazex syndrome.
Bazex’s acrokeratosis paraneoplastica. Ann Otol J Laryngol Otol. 1996;110:899–900.
Rhinol Laryngol. 1996;105:487–9.
33. Hodge L, Marsden RA, Black MM, Bhogal B, Corbett
20. Bazex A, Salvador R, Dupré A, Christol B. Syndrome MF. Bullous pemphigoid: the frequency of mucosal
paranéoplasique à type d’hyperkératose des extré- involvement and concurrent malignancy related to
mités. Guérison après le traitement de l’épithélioma indirect immunofluorescence findings. Br J Derma-
laryngé. Bull Soc Fr Dermatol Syphil. 1965;72:182. tol. 1981;105:65–9.

21. Bazex J, El Sayed F, Sans B, Marguery MC, Samalens 34. Balestri R, Magnano M, La Placa M, et al. Malig-
G. Acrokératose paranéoplasique de Bazex associée a nancies in bullous pemphigoid: a controversial
une ichtyose acquise, des troubles de la pigmenta- association. J Dermatol. 2016;43:125–33.
tion et un prurit: révélation tardive d’un néoplasme
laryngé. Ann Dermatol Venereol. 1992;119:483–5. 35. Bonnetblanc JM, Bernard P, Fayol J. Dermato-
myositis and malignancy: a multicenter cooperative
22. Blanchet F, Leroy D, Deschamps P. Acrokératose study. Dermatologica. 1990;180:212–6.
paranéoplasique de Bazex. A propos de 8 cas. J Fr
Otorhinolaryngol. 1980;29:165–72. 36. Mackenzie AH, Scherbel AL. Connective tissue
syndromes associated with carcinoma. Geriatrics.
23. Colomb D, Reboul MC, Mauduit G, Forestier JY. 1963;18:745–53.
Forme diffuse d’acrokératose paranéoplasique de
Bazex révélatrice d’une récidive et de métastases 37. Guin JD, Elleman JH. Yellow nail syndrome. Possi-
d’un cancer de l’épiglotte antérieurement traité. ble association with malignancy. Arch Dermatol.
Ann Dermatol Venereol. 1981;108:885–8. 1979;115:734–5.

24. Gaillard J, Haguenauer JP, Dubreuil C, Romanet P. 38. Haines D. Primary carcinoma duplex associated
Acrokératose de Bazex, syndrome paranéoplasique with tylosis. J R Nav Med Serv. 1967;53:75–8.
révélateur d’une métastase d’un cancer de la vallé-
cule guéri localement à trois ans. J Fr Otorhino- 39. Batinac T, Kujundzić M, Peternel S, Cabrijan L,
laryngol. 1978;27:353–7. Troselj-Vukić B, Petranović D. Pityriasis rubra pilaris
in association with laryngeal carcinoma. Clin Exp
25. Legros M, Kalis B, Brunetaud P, Longuebray A. Dermatol. 2009;34:e917–9.
Cancer pharyngo-laryngé et acrokératose de Bazex.
Ann Otolaryngol Chir Cervicofac. 1977;94:47–52.
Adv Ther

40. Nyati A, Kalwaniya S, Jain S, Soni B. Sign of Leser- 54. Kandylis KV, Vasilomanolakis M, Efremides AD.
Trélat in association with laryngeal carcinoma. Syndrome of inappropriate antidiuretic hormone
Indian J Dermatol Venereol Leprol. 2016;82:112. secretion in pyriform sinus squamous cell carci-
noma. Am J Med. 1986;81:946.
41. Soga J. Carcinoids and their variant endocrinomas.
An analysis of 11842 reported cases. J Exp Clin 55. Moses AM, Miller M, Streeten DHP. Pathophysio-
Cancer Res. 2003;22:517–30. logic and pharmacologic alterations in the release
and action of ADH. Metabolism. 1976;25:697–721.
42. Soga J. Early-stage carcinoids of the gastrointestinal
tract: an analysis of 1914 reported cases. Cancer. 56. Roth Y, Lightman SL, Kronenberg J. Hyponatremia
2005;103:1587–895. associated with laryngeal squamous cell carcinoma.
Eur Arch Otorhinolaryngol. 1994;251:183–5.
43. Soga J, Yakuwa Y, Osaka M. Carcinoid syndrome: a
statistical evaluation of 748 reported cases. J Exp 57. Talmi YP, Hoffman HT, McCabe BF. Syndrome of
Clin Cancer Res. 1999;18:133–41. inappropriate secretion of arginine vasopressin in
patients with cancer of the head and neck. Ann
44. Ferlito A, Rinaldo A. The spectrum of Otol Rhinol Laryngol. 1992;101:946–9.
endocrinocarcinomas of the larynx. Oral Oncol.
2005;41:878–83. 58. Zohar Y, Talmi YP, Finkelstein Y, Nobel M, Gafter U.
The syndrome of inappropriate antidiuretic hor-
45. Ferlito A, Devaney KO, Rinaldo A. Neuroendocrine mone secretion in cancer of the head and neck. Ann
neoplasms of the larynx: advances in identification, Otol Rhinol Laryngol. 1991;100:341–4.
understanding and management. Oral Oncol.
2006;42:770–88. 59. Trotoux J, Glickmanas M, Sterkers O, Trousset M,
Pinel J. Syndrome de Schwartz-Bartter: révélateur
46. Baugh RF, Wolf GT, Lloyd RV, McClatchey KD, d’un cancer laryngé sousglottique à petites cellules.
Evans DA. Carcinoid (neuroendocrine carcinoma) Ann Otolaryngol Chir Cervicofac. 1979;96:349–58.
of the larynx. Ann Otol Rhinol Laryngol. 1987;96:
315–21. 60. Takeuchi K, Nishii S, Jin CS, Ukai K, Sakakura Y.
Anaplastic small cell carcinoma of the larynx. Auris
47. Kumai M, Arakawa T, Nakane T, et al. Serum sero- Nasus Larynx. 1989;16:127–32.
tonin elevated carcinoid tumor of the larynx (in
Japanese). Larynx Jpn. 1996;8:53–5. 61. Myers TJ, Kessimian N. Small cell carcinoma of the
larynx and ectopic antidiuretic hormone secretion.
48. Overholt SM, Donovan DT, Schwartz MR, Laucirica Otolaryngol Head Neck Surg. 1995;113:301–4.
R, Green LK, Alford BR. Neuroendocrine neoplasms
of the larynx. Laryngoscope. 1995;105:789–94. 62. Mundy GR. Ectopic production of calciotropic
peptides. Endocrinol Metab Clin N Am. 1991;20:
49. Wenig BM, Gnepp DR. The spectrum of neuroen- 473–87.
docrine carcinomas of the larynx. Semin Diagn
Pathol. 1989;6:329–50. 63. Mundy GR, Ibbotson KJ, D’Souza SM, Simpson EL,
Jacobs JW, Martin TJ. The hypercalcemia of cancer:
50. Yamanaka J, Yao K, Kohno H. A case of primary clinical implications and pathogenic mechanisms.
laryngeal carcinoid with the carcinoid syndrome N Engl J Med. 1984;310:1718–27.
and rapid clinical course (in Japanese). Kitasato
Med. 1997;27:110–3. 64. Plimpton CH, Gellhorn A. Hypercalcemia in
malignant disease without evidence of bone
51. Imura H, Matsukura S, Yamamoto H, Hirata Y, destruction. Am J Med. 1956;21:750–9.
Nakai Y. Studies on ectopic ACTH-producing
tumors. II. Clinical and biochemical features of 30 65. Angel MF, Stewart A, Pensak ML, Pillsbury HRC,
cases. Cancer. 1975;35:1430–7. Sasaki CT. Mechanisms of hypercalcemia in
patients with head and neck cancer. Head Neck
52. Bishop JW, Osamura RY, Tsutsumi Y. Multiple Surg. 1982;5:125–9.
hormone production in an oat cell carcinoma of the
larynx. Acta Pathol Jpn. 1985;35:915–23. 66. Zhang R, Li J, Assaker G, et al. Parathyroid hor-
mone-related protein (PTHrP): an emerging target
53. Schwartz WB, Warren B, Curelop S, Bartter FC. A in cancer progression and metastasis. Adv Exp Med
syndrome of renal sodium loss and hyponatremia Biol. 2019;1164:161–78.
probably resulting from inappropriate secretion of
antidiuretic hormone. Am J Med. 1957;23:529–42. 67. Minotti AM, Kountakis SE, Stiernberg CM. Parane-
oplastic syndromes in patients with head and neck
cancer. Am J Otolaryngol. 1994;15:336–43.
 Adv Ther

68. Trousseau A. Phlegmasia alba dolens. Clinique 82. Seute T, Leffers P, ten Velde GP, Twijnstra A. Neu-
Medicale de l’Hôtel-Dieu de Paris, vol. 3. London: rologic disorders in 432 consecutive patients with
New Sydenham Society; 1865. small cell lung carcinoma. Cancer. 2004;100:801–6.

69. Evans TRJ, Mansi JL, Bevan DH. Trousseau’s syn- 83. Fontanel J-P, Betheuil MJ, Sénéchal G, Haguenau M.
drome in association with ovarian carcinoma. Un cas de syndrome de Lambert-Eaton secondaire à
Cancer. 1996;77:2544–9. un épithélioma laryngé. Ann Otolaryngol Chir
Cervicofac. 1973;90:314–7.
70. Sack GH Jr, Levin J, Bell WR. Trousseau’s syndrome
and other manifestations of chronic disseminated 84. Medina JE, Moran M, Goepfert H. Oat cell carci-
coagulopathy in patients with neoplasms: clinical, noma of the larynx and Eaton–Lambert syndrome.
pathophysiologic, and therapeutic features. Medi- Arch Otolaryngol. 1984;110:123–6.
cine (Baltimore). 1977;56:1–37.
85. Ferroir JP, Hervier-Caen C, Reignier A, Nicolle MH,
71. Nikšic M, Balogh M. Über Gerinnungsstörungen bei Guillard A. [Remission of Lambert–Eaton syndrome
Kehlkopf- und Rachen-Malignomen. Laryngorhi- over a 10-year period. Recurrence without evidence
nootologie. 1976;55:414–9. of tumor at autopsy]. Rev Neurol (Paris). 1989;145:
851–2. (Article in French).
72. Naschitz JE, Yeshurun D, Eldar S, Lev LM. Diagnosis
of cancer-associated vascular disorders. Cancer. 86. Shipley E, Krim E, Deminière C, Lagueny A. [Lam-
1996;77:1759–67. bert–Eaton myasthenic syndrome associated with
vocal cord carcinoma]. Rev Neurol (Paris).
73. Liu PG, Jacobs JB, Reede D. Trousseau’s syndrome in 2008;164:72–6. (Article in French).
the head and neck. Am J Otolaryngol. 1985;6:
405–8. 87. Wymenga AN, Slebos DJ, van der Naalt J, van Put-
ten JW, Peters FT. [Abdominal complaints and
74. Garcin R, Lapresle J. Sur un cas d’atrophie céré- neurological symptoms as an early sign of lung
belleuse corticale subaigue en relation avec un épi- cancer: a manifestation of the anti-Hu syndrome].
thélioma du larynx. Arch Pathol. 1956;62:399–402. Ned Tijdschr Geneeskd. 2003;147:616–9. (Article in
Dutch).
75. Müller E, Spanke O, Lehmann I. Neurogene
Störungen bei extrazerebralen Malignomen. Med 88. Baijens LW, Manni JJ. Paraneoplastic syndromes in
Klin. 1969;64:1470–5. patients with primary malignancies of the head and
neck. Four cases and a review of the literature. Eur
76. Baloh RW. Paraneoplastic cerebellar disorders. Arch Otorhinolaryngol. 2006;263:32–6.
Otolaryngol Head Neck Surg. 1995;112:125–7.
89. Erro Aguirre ME, Gila L, Olaziregui O. [Paraneo-
77. Cher LM, Hochberg FH, Teruya J, et al. Therapy for plastic sensory neuropathy associated with squa-
paraneoplastic neurologic syndromes in six patients mous cell carcinoma of the larynx]. Neurologia.
with protein A column immunoadsorption. Cancer. 2016;31:286–8. (Article in Spanish).
1995;75:1678–83.
90. Stummvoll GH, Aringer M, Machold KP, Smolen JS,
78. Garcia FJ, Blazquez JA, Perez-Moro E, Martinez S. Raderer M. Cancer polyarthritis resembling
[Paraneoplastic ataxia due to laryngeal carcinoma]. rheumatoid arthritis as a first sign of hidden neo-
Acta Otorrinolaringol Esp. 1998;49:414–5. (Article plasms. Report of two cases and review of the liter-
in Spanish). ature. Scand J Rheumatol. 2001;30:40–4.

79. Lambert E, Eaton L, Rooke E. Defect of neuromus- 91. Eggelmeijer F, Macfarlane JD. Polyarthritis as the
cular conduction associated with malignant neo- presenting symptom of the occurrence and recur-
plasm. Am J Physiol. 1956;187:612. rence of a laryngeal carcinoma. Ann Rheum Dis.
1992;51:556–7.
80. Eaton LM, Lambert EH. Electromyography and
electric stimulation of nerves in diseases of motor 92. Cabane J, Lebas J, Wattiaux MJ, Imbert JC. [Pseudo-
unit: observation on the myasthenic syndrome Still disease and neoplasm. 2 cases]. Rev Med
associated with malignant tumors. JAMA. 1957;183: Interne. 1988;9:81–4. (Article in French).
183–99.
93. Cohen PR. Hypertrophic pulmonary
81. Gray TC, Halton J. Idiosyncracy to d-tubocurarine osteoarthropathy and tripe palms in a man with
chloride. Br Med J. 1948;1:784–6. squamous cell carcinoma of the larynx and lung.
Report of a case and review of cutaneous paraneo-
plastic syndromes associated with laryngeal and
Adv Ther

lung malignancies. Am J Clin Oncol. 1993;16: 98. Rubisz-Brzezinska J, Zebracka T, Musialowicz D.

268–76. Coexistence of 2 paraneoplastic syndromes—acro-
keratosis Bazex and Leser-Trèlat syndrome—in a
94. Bataller L, Dalmau J. Neuro-ophthalmology and case of squamous-cell laryngeal cancer. Przegl Der-
paraneoplastic syndromes. Curr Opin Neurol. matol. 1983;70:205–8.
2004;17:3–8.
99. Ehmann LM, Grahovac M, Kramer M, Ruzicka T,
95. Parc CE, Azan E, Bonnel S, Sahel JA, Kaplan J, Wollenberg A. Paraneoplastic palmoplantar hyper-
Thirkill CE. Cone dysfunction as a paraneoplastic keratosis. Minor form of acrokeratosis neoplastica
syndrome associated with retinal antigens approxi- Bazex? Hautarzt. 2012;63:477–9.
mating 40 kiloDalton. Ophthalmic Genet. 2006;27:
57–61. 100. Tsvetkov EA. [Dermatomyositis as a complication of
the radiotherapy of laryngeal cancer]. Med Radiol
96. Hill CL, Zhang Y, Sigurgeirsson B, et al. Frequency (Mosk). 1977;22:78–9. (Article in Russian).
of specific cancer types in dermatomyositis and
polymyositis: a population-based study. Lancet. 101. Zhang W, Jiang SP, Huang L. Dermatomyositis and
2001;357:96–100. malignancy: a retrospective study of 115 cases. Eur
Rev Med Pharmacol Sci. 2009;13:77–80.
97. Sahu R, Rathaur BP, Chaudhari TS, Shukla R, Mal-
hotra KP. Laryngeal carcinoma presenting as 102. Maxwell EL, Witterick IJ. Syndrome of inappropri-
polymyositis: a paraneoplastic syndrome. Ann ate antidiuretic hormone in a patient with meta-
Indian Acad Neurol. 2016;19:150–1. static supraglottic cancer. J Otolaryngol. 2004;33:
308–9.